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Sample records for reveals phase-specific control

  1. Genome-wide and phase-specific DNA-binding rhythms of BMAL1 control circadian output functions in mouse liver.

    Directory of Open Access Journals (Sweden)

    Guillaume Rey

    2011-02-01

    Full Text Available The mammalian circadian clock uses interlocked negative feedback loops in which the heterodimeric basic helix-loop-helix transcription factor BMAL1/CLOCK is a master regulator. While there is prominent control of liver functions by the circadian clock, the detailed links between circadian regulators and downstream targets are poorly known. Using chromatin immunoprecipitation combined with deep sequencing we obtained a time-resolved and genome-wide map of BMAL1 binding in mouse liver, which allowed us to identify over 2,000 binding sites, with peak binding narrowly centered around Zeitgeber time 6. Annotation of BMAL1 targets confirms carbohydrate and lipid metabolism as the major output of the circadian clock in mouse liver. Moreover, transcription regulators are largely overrepresented, several of which also exhibit circadian activity. Genes of the core circadian oscillator stand out as strongly bound, often at promoter and distal sites. Genomic sequence analysis of the sites identified E-boxes and tandem E1-E2 consensus elements. Electromobility shift assays showed that E1-E2 sites are bound by a dimer of BMAL1/CLOCK heterodimers with a spacing-dependent cooperative interaction, a finding that was further validated in transactivation assays. BMAL1 target genes showed cyclic mRNA expression profiles with a phase distribution centered at Zeitgeber time 10. Importantly, sites with E1-E2 elements showed tighter phases both in binding and mRNA accumulation. Finally, analyzing the temporal profiles of BMAL1 binding, precursor mRNA and mature mRNA levels showed how transcriptional and post-transcriptional regulation contribute differentially to circadian expression phase. Together, our analysis of a dynamic protein-DNA interactome uncovered how genes of the core circadian oscillator crosstalk and drive phase-specific circadian output programs in a complex tissue.

  2. Cell-cycle phase specificity of chloroethylnitrosoureas

    International Nuclear Information System (INIS)

    Linfoot, P.A.

    1986-01-01

    Although the cancer chemotherapeutic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) is considered a non-cell cycle phase specific drug, it has been shown to produce differential cell killing in G 1 , S, and G 2 /M phase cells, with S phase cells appearing relatively resistant. Studies of cell cycle phase specific cell killing produced by nitrosoureas with different chemical reactivities, clearly indicated that the ability of compounds to cross-link DNA was important in determining their phase specificity. Cells that lacked guanine O 6 -alkytransferase activity showed similar patterns of BCNU phase specificity regardless of their intrinsic sensitivity to BCNU. DNA inter-strand cross-linking, as measured by alkaline elution, was similar in cells exposed to BCNU in G 1 or S phase. 3 H [1-chloroethyl-1nitrosourea] binding to DNA was the same in G 1 , S and G 2 /M phase cells indicating that phase-specific differences in drug uptake and intracellular drug dose were not responsible for phase specific cell kill. These studies suggest that cross-link lesions, other than DNA inter-strand cross-links, and/or effects on DNA repair, other than guanine O 6 -alkyltransferase, are additional important determinants of BCNU phase specific cell killing

  3. The freeze-thaw stress response of the yeast Saccharomyces cerevisiae is growth phase specific and is controlled by nutritional state via the RAS-cyclic AMP signal transduction pathway.

    Science.gov (United States)

    Park, J I; Grant, C M; Attfield, P V; Dawes, I W

    1997-10-01

    The ability of cells to survive freezing and thawing is expected to depend on the physiological conditions experienced prior to freezing. We examined factors affecting yeast cell survival during freeze-thaw stress, including those associated with growth phase, requirement for mitochondrial functions, and prior stress treatment(s), and the role played by relevant signal transduction pathways. The yeast Saccharomyces cerevisiae was frozen at -20 degrees C for 2 h (cooling rate, less than 4 degrees C min-1) and thawed on ice for 40 min. Supercooling occurred without reducing cell survival and was followed by freezing. Loss of viability was proportional to the freezing duration, indicating that freezing is the main determinant of freeze-thaw damage. Regardless of the carbon source used, the wild-type strain and an isogenic petite mutant ([rho 0]) showed the same pattern of freeze-thaw tolerance throughout growth, i.e., high resistance during lag phase and low resistance during log phase, indicating that the response to freeze-thaw stress is growth phase specific and not controlled by glucose repression. In addition, respiratory ability and functional mitochondria are necessary to confer full resistance to freeze-thaw stress. Both nitrogen and carbon source starvation led to freeze-thaw tolerance. The use of strains affected in the RAS-cyclic AMP (RAS-cAMP) pathway or supplementation of an rca1 mutant (defective in the cAMP phosphodiesterase gene) with cAMP showed that the freeze-thaw response of yeast is under the control of the RAS-cAMP pathway. Yeast did not adapt to freeze-thaw stress following repeated freeze-thaw treatment with or without a recovery period between freeze-thaw cycles, nor could it adapt following pretreatment by cold shock. However, freeze-thaw tolerance of yeast cells was induced during fermentative and respiratory growth by pretreatment with H2O2, cycloheximide, mild heat shock, or NaCl, indicating that cross protection between freeze-thaw stress

  4. Bell trajectories for revealing quantum control mechanisms

    International Nuclear Information System (INIS)

    Dennis, Eric; Rabitz, Herschel

    2003-01-01

    The dynamics induced while controlling quantum systems by optimally shaped laser pulses have often been difficult to understand in detail. A method is presented for quantifying the importance of specific sequences of quantum transitions involved in the control process. The method is based on a ''beable'' formulation of quantum mechanics due to John Bell that rigorously maps the quantum evolution onto an ensemble of stochastic trajectories over a classical state space. Detailed mechanism identification is illustrated with a model seven-level system. A general procedure is presented to extract mechanism information directly from closed-loop control experiments. Application to simulated experimental data for the model system proves robust with up to 25% noise

  5. RNAi Reveals Phase-Specific Global Regulators of Human Somatic Cell Reprogramming

    Directory of Open Access Journals (Sweden)

    Cheng-Xu Delon Toh

    2016-06-01

    Full Text Available Incomplete knowledge of the mechanisms at work continues to hamper efforts to maximize reprogramming efficiency. Here, we present a systematic genome-wide RNAi screen to determine the global regulators during the early stages of human reprogramming. Our screen identifies functional repressors and effectors that act to impede or promote the reprogramming process. Repressors and effectors form close interacting networks in pathways, including RNA processing, G protein signaling, protein ubiquitination, and chromatin modification. Combinatorial knockdown of five repressors (SMAD3, ZMYM2, SFRS11, SAE1, and ESET synergistically resulted in ∼85% TRA-1-60-positive cells. Removal of the novel splicing factor SFRS11 during reprogramming is accompanied by rapid acquisition of pluripotency-specific spliced forms. Mechanistically, SFRS11 regulates exon skipping and mutually exclusive splicing of transcripts in genes involved in cell differentiation, mRNA splicing, and chromatin modification. Our study provides insights into the reprogramming process, which comprises comprehensive and multi-layered transcriptional, splicing, and epigenetic machineries.

  6. Stimulating at the right time: phase-specific deep brain stimulation.

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    Cagnan, Hayriye; Pedrosa, David; Little, Simon; Pogosyan, Alek; Cheeran, Binith; Aziz, Tipu; Green, Alexander; Fitzgerald, James; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Friston, Karl J; Denison, Timothy; Brown, Peter

    2017-01-01

    SEE MOLL AND ENGEL DOI101093/AWW308 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Brain regions dynamically engage and disengage with one another to execute everyday actions from movement to decision making. Pathologies such as Parkinson's disease and tremor emerge when brain regions controlling movement cannot readily decouple, compromising motor function. Here, we propose a novel stimulation strategy that selectively regulates neural synchrony through phase-specific stimulation. We demonstrate for the first time the therapeutic potential of such a stimulation strategy for the treatment of patients with pathological tremor. Symptom suppression is achieved by delivering stimulation to the ventrolateral thalamus, timed according to the patient's tremor rhythm. Sustained locking of deep brain stimulation to a particular phase of tremor afforded clinically significant tremor relief (up to 87% tremor suppression) in selected patients with essential tremor despite delivering less than half the energy of conventional high frequency stimulation. Phase-specific stimulation efficacy depended on the resonant characteristics of the underlying tremor network. Selective regulation of neural synchrony through phase-locked stimulation has the potential to both increase the efficiency of therapy and to minimize stimulation-induced side effects. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

  7. Representational Similarity Analysis Reveals Heterogeneous Networks Supporting Speech Motor Control

    DEFF Research Database (Denmark)

    Zheng, Zane; Cusack, Rhodri; Johnsrude, Ingrid

    The everyday act of speaking involves the complex processes of speech motor control. One important feature of such control is regulation of articulation when auditory concomitants of speech do not correspond to the intended motor gesture. While theoretical accounts of speech monitoring posit...... multiple functional components required for detection of errors in speech planning (e.g., Levelt, 1983), neuroimaging studies generally indicate either single brain regions sensitive to speech production errors, or small, discrete networks. Here we demonstrate that the complex system controlling speech...... is supported by a complex neural network that is involved in linguistic, motoric and sensory processing. With the aid of novel real-time acoustic analyses and representational similarity analyses of fMRI signals, our data show functionally differentiated networks underlying auditory feedback control of speech....

  8. Network analysis reveals multiscale controls on streamwater chemistry

    Science.gov (United States)

    McGuire, Kevin J.; Torgersen, Christian E.; Likens, Gene E.; Buso, Donald C.; Lowe, Winsor H.; Bailey, Scott W.

    2014-01-01

    By coupling synoptic data from a basin-wide assessment of streamwater chemistry with network-based geostatistical analysis, we show that spatial processes differentially affect biogeochemical condition and pattern across a headwater stream network. We analyzed a high-resolution dataset consisting of 664 water samples collected every 100 m throughout 32 tributaries in an entire fifth-order stream network. These samples were analyzed for an exhaustive suite of chemical constituents. The fine grain and broad extent of this study design allowed us to quantify spatial patterns over a range of scales by using empirical semivariograms that explicitly incorporated network topology. Here, we show that spatial structure, as determined by the characteristic shape of the semivariograms, differed both among chemical constituents and by spatial relationship (flow-connected, flow-unconnected, or Euclidean). Spatial structure was apparent at either a single scale or at multiple nested scales, suggesting separate processes operating simultaneously within the stream network and surrounding terrestrial landscape. Expected patterns of spatial dependence for flow-connected relationships (e.g., increasing homogeneity with downstream distance) occurred for some chemical constituents (e.g., dissolved organic carbon, sulfate, and aluminum) but not for others (e.g., nitrate, sodium). By comparing semivariograms for the different chemical constituents and spatial relationships, we were able to separate effects on streamwater chemistry of (i) fine-scale versus broad-scale processes and (ii) in-stream processes versus landscape controls. These findings provide insight on the hierarchical scaling of local, longitudinal, and landscape processes that drive biogeochemical patterns in stream networks.

  9. Network analysis reveals multiscale controls on streamwater chemistry.

    Science.gov (United States)

    McGuire, Kevin J; Torgersen, Christian E; Likens, Gene E; Buso, Donald C; Lowe, Winsor H; Bailey, Scott W

    2014-05-13

    By coupling synoptic data from a basin-wide assessment of streamwater chemistry with network-based geostatistical analysis, we show that spatial processes differentially affect biogeochemical condition and pattern across a headwater stream network. We analyzed a high-resolution dataset consisting of 664 water samples collected every 100 m throughout 32 tributaries in an entire fifth-order stream network. These samples were analyzed for an exhaustive suite of chemical constituents. The fine grain and broad extent of this study design allowed us to quantify spatial patterns over a range of scales by using empirical semivariograms that explicitly incorporated network topology. Here, we show that spatial structure, as determined by the characteristic shape of the semivariograms, differed both among chemical constituents and by spatial relationship (flow-connected, flow-unconnected, or Euclidean). Spatial structure was apparent at either a single scale or at multiple nested scales, suggesting separate processes operating simultaneously within the stream network and surrounding terrestrial landscape. Expected patterns of spatial dependence for flow-connected relationships (e.g., increasing homogeneity with downstream distance) occurred for some chemical constituents (e.g., dissolved organic carbon, sulfate, and aluminum) but not for others (e.g., nitrate, sodium). By comparing semivariograms for the different chemical constituents and spatial relationships, we were able to separate effects on streamwater chemistry of (i) fine-scale versus broad-scale processes and (ii) in-stream processes versus landscape controls. These findings provide insight on the hierarchical scaling of local, longitudinal, and landscape processes that drive biogeochemical patterns in stream networks.

  10. Controllability analysis of transcriptional regulatory networks reveals circular control patterns among transcription factors

    DEFF Research Database (Denmark)

    Österlund, Tobias; Bordel, Sergio; Nielsen, Jens

    2015-01-01

    % for the human network. The high controllability (low number of drivers needed to control the system) in yeast, mouse and human is due to the presence of internal loops in their regulatory networks where the TFs regulate each other in a circular fashion. We refer to these internal loops as circular control...... motifs (CCM). The E. coli transcriptional regulatory network, which does not have any CCMs, shows a hierarchical structure of the transcriptional regulatory network in contrast to the eukaryal networks. The presence of CCMs also has influence on the stability of these networks, as the presence of cycles...

  11. Feedback Control of Sex Determination by Dosage Compensation Revealed through Caenorhabditis Elegans Sdc-3 Mutations

    OpenAIRE

    DeLong, L.; Plenefisch, J. D.; Klein, R. D.; Meyer, B. J.

    1993-01-01

    In Caenorhabditis elegans, sex determination and dosage compensation are coordinately controlled through a group of genes that respond to the primary sex determination signal. Here we describe a new gene, sdc-3, that also controls these processes. In contrast to previously described genes, the sex determination and dosage compensation activities of sdc-3 are separately mutable, indicating that they function independently. Paradoxically, the sdc-3 null phenotype fails to reveal the role of sdc...

  12. Delay equations modeling the effects of phase-specific drugs and immunotherapy on proliferating tumor cells.

    Science.gov (United States)

    Barbarossa, Maria Vittoria; Kuttler, Christina; Zinsl, Jonathan

    2012-04-01

    In this work we present a mathematical model for tumor growth based on the biology of the cell cycle. For an appropriate description of the effects of phase-specific drugs, it is necessary to look at the cell cycle and its phases. Our model reproduces the dynamics of three different tumor cell populations: quiescent cells, cells during the interphase and mitotic cells. Starting from a partial differential equations (PDEs) setting, a delay differential equations (DDE) model is derived for an easier and more realistic approach. Our equations also include interactions of tumor cells with immune system effectors. We investigate the model both from the analytical and the numerical point of view, give conditions for positivity of solutions and focus on the stability of the cancer-free equilibrium. Different immunotherapeutic strategies and their effects on the tumor growth are considered, as well.

  13. fMRI of Simultaneous Interpretation Reveals the Neural Basis of Extreme Language Control.

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    Hervais-Adelman, Alexis; Moser-Mercer, Barbara; Michel, Christoph M; Golestani, Narly

    2015-12-01

    We used functional magnetic resonance imaging (fMRI) to examine the neural basis of extreme multilingual language control in a group of 50 multilingual participants. Comparing brain responses arising during simultaneous interpretation (SI) with those arising during simultaneous repetition revealed activation of regions known to be involved in speech perception and production, alongside a network incorporating the caudate nucleus that is known to be implicated in domain-general cognitive control. The similarity between the networks underlying bilingual language control and general executive control supports the notion that the frequently reported bilingual advantage on executive tasks stems from the day-to-day demands of language control in the multilingual brain. We examined neural correlates of the management of simultaneity by correlating brain activity during interpretation with the duration of simultaneous speaking and hearing. This analysis showed significant modulation of the putamen by the duration of simultaneity. Our findings suggest that, during SI, the caudate nucleus is implicated in the overarching selection and control of the lexico-semantic system, while the putamen is implicated in ongoing control of language output. These findings provide the first clear dissociation of specific dorsal striatum structures in polyglot language control, roles that are consistent with previously described involvement of these regions in nonlinguistic executive control. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Self-regulation following prostatectomy : Phase-specific self-efficacy beliefs in implementing pelvic-floor exercise

    OpenAIRE

    Burkert, Silke; Knoll, Nina; Scholz, Urte; Roigas, Jan; Gralla, Oliver

    2012-01-01

    Beliefs in one's ability to perform a task or behaviour successfully are described as self-efficacy beliefs (Bandura, 1977). Since individuals have to deal with differing demands during a behaviour-change process, they form phase-specific self-efficacy beliefs directed at these respective challenges. The present study, based on the Health Action Process Approach (Schwarzer, 2001), examines the theoretical differentiation, relative importance, and differential effects of four phase-specific se...

  15. Application of REVEAL-W to risk-based configuration control

    International Nuclear Information System (INIS)

    Dezfuli, H.; Meyer, J.; Modarres, M.

    1994-01-01

    Over the past two years, the concept of risk-based configuration control has been introduced to the US Nuclear Regulatory Commission and the nuclear industry. Converting much of the current, deterministically based regulation of nuclear power plants to risk-based regulation can result in lower levels of risk while relieving unnecessary burdens on power plant operators and regulatory staff. To achieve the potential benefits of risk-based configuration control, the risk models developed for nuclear power plants should be (1) flexible enough to effectively support necessary risk calculations, and (2) transparent enough to encourage their use by all parties. To address these needs, SCIENTECH, Inc., has developed the PC-based REVEAL W (formerly known as SMART). This graphic-oriented and user-friendly application software allows the user to develop transparent complex logic models based on the concept of the master plant logic diagram. The logic model is success-oriented and compact. The analytical capability built into REVEAL W is generic, so the software can support different types of risk-based evaluations, such as probabilistic safety assessment, accident sequence precursor analysis, design evaluation and configuration management. In this paper, we focus on the application of REVEAL W to support risk-based configuration control of nuclear power plants. (author)

  16. Analysis of clock-regulated genes in Neurospora reveals widespread posttranscriptional control of metabolic potential

    Science.gov (United States)

    Hurley, Jennifer M.; Dasgupta, Arko; Emerson, Jillian M.; Zhou, Xiaoying; Ringelberg, Carol S.; Knabe, Nicole; Lipzen, Anna M.; Lindquist, Erika A.; Daum, Christopher G.; Barry, Kerrie W.; Grigoriev, Igor V.; Smith, Kristina M.; Galagan, James E.; Bell-Pedersen, Deborah; Freitag, Michael; Cheng, Chao; Loros, Jennifer J.; Dunlap, Jay C.

    2014-01-01

    Neurospora crassa has been for decades a principal model for filamentous fungal genetics and physiology as well as for understanding the mechanism of circadian clocks. Eukaryotic fungal and animal clocks comprise transcription-translation–based feedback loops that control rhythmic transcription of a substantial fraction of these transcriptomes, yielding the changes in protein abundance that mediate circadian regulation of physiology and metabolism: Understanding circadian control of gene expression is key to understanding eukaryotic, including fungal, physiology. Indeed, the isolation of clock-controlled genes (ccgs) was pioneered in Neurospora where circadian output begins with binding of the core circadian transcription factor WCC to a subset of ccg promoters, including those of many transcription factors. High temporal resolution (2-h) sampling over 48 h using RNA sequencing (RNA-Seq) identified circadianly expressed genes in Neurospora, revealing that from ∼10% to as much 40% of the transcriptome can be expressed under circadian control. Functional classifications of these genes revealed strong enrichment in pathways involving metabolism, protein synthesis, and stress responses; in broad terms, daytime metabolic potential favors catabolism, energy production, and precursor assembly, whereas night activities favor biosynthesis of cellular components and growth. Discriminative regular expression motif elicitation (DREME) identified key promoter motifs highly correlated with the temporal regulation of ccgs. Correlations between ccg abundance from RNA-Seq, the degree of ccg-promoter activation as reported by ccg-promoter–luciferase fusions, and binding of WCC as measured by ChIP-Seq, are not strong. Therefore, although circadian activation is critical to ccg rhythmicity, posttranscriptional regulation plays a major role in determining rhythmicity at the mRNA level. PMID:25362047

  17. A multi-scale model of hepcidin promoter regulation reveals factors controlling systemic iron homeostasis.

    Directory of Open Access Journals (Sweden)

    Guillem Casanovas

    2014-01-01

    Full Text Available Systemic iron homeostasis involves a negative feedback circuit in which the expression level of the peptide hormone hepcidin depends on and controls the iron blood levels. Hepcidin expression is regulated by the BMP6/SMAD and IL6/STAT signaling cascades. Deregulation of either pathway causes iron-related diseases such as hemochromatosis or anemia of inflammation. We quantitatively analyzed how BMP6 and IL6 control hepcidin expression. Transcription factor (TF phosphorylation and reporter gene expression were measured under co-stimulation conditions, and the promoter was perturbed by mutagenesis. Using mathematical modeling, we systematically analyzed potential mechanisms of cooperative and competitive promoter regulation by the transcription factors, and experimentally validated the model predictions. Our results reveal that hepcidin cross-regulation primarily occurs by combinatorial transcription factor binding to the promoter, whereas signaling crosstalk is insignificant. We find that the presence of two BMP-responsive elements enhances the steepness of the promoter response towards the iron-sensing BMP signaling axis, which promotes iron homeostasis in vivo. IL6 co-stimulation reduces the promoter sensitivity towards the BMP signal, because the SMAD and STAT transcription factors compete for recruiting RNA polymerase to the transcription start site. This may explain why inflammatory signals disturb iron homeostasis in anemia of inflammation. Taken together, our results reveal why the iron homeostasis circuit is sensitive to perturbations implicated in disease.

  18. Mechanism for G2 phase-specific nuclear export of the kinetochore protein CENP-F.

    Science.gov (United States)

    Loftus, Kyle M; Cui, Heying; Coutavas, Elias; King, David S; Ceravolo, Amanda; Pereiras, Dylan; Solmaz, Sozanne R

    2017-08-03

    Centromere protein F (CENP-F) is a component of the kinetochore and a regulator of cell cycle progression. CENP-F recruits the dynein transport machinery and orchestrates several cell cycle-specific transport events, including transport of the nucleus, mitochondria and chromosomes. A key regulatory step for several of these functions is likely the G2 phase-specific export of CENP-F from the nucleus to the cytosol, where the cytoplasmic dynein transport machinery resides; however, the molecular mechanism of this process is elusive. Here, we have identified 3 phosphorylation sites within the bipartite classical nuclear localization signal (cNLS) of CENP-F. These sites are specific for cyclin-dependent kinase 1 (Cdk1), which is active in G2 phase. Phosphomimetic mutations of these residues strongly diminish the interaction of the CENP-F cNLS with its nuclear transport receptor karyopherin α. These mutations also diminish nuclear localization of the CENP-F cNLS in cells. Notably, the cNLS is phosphorylated in the -1 position, which is important to orient the adjacent major motif for binding into its pocket on karyopherin α. We propose that localization of CENP-F is regulated by a cNLS, and a nuclear export pathway, resulting in nuclear localization during most of interphase. In G2 phase, the cNLS is weakened by phosphorylation through Cdk1, likely resulting in nuclear export of CENP-F via the still active nuclear export pathway. Once CENP-F resides in the cytosol, it can engage in pathways that are important for cell cycle progression, kinetochore assembly and the faithful segregation of chromosomes into daughter cells.

  19. Data-driven analysis of simultaneous EEG/fMRI reveals neurophysiological phenotypes of impulse control.

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    Schmüser, Lena; Sebastian, Alexandra; Mobascher, Arian; Lieb, Klaus; Feige, Bernd; Tüscher, Oliver

    2016-09-01

    Response inhibition is the ability to suppress inadequate but prepotent or ongoing response tendencies. A fronto-striatal network is involved in these processes. Between-subject differences in the intra-individual variability have been suggested to constitute a key to pathological processes underlying impulse control disorders. Single-trial EEG/fMRI analysis allows to increase sensitivity for inter-individual differences by incorporating intra-individual variability. Thirty-eight healthy subjects performed a visual Go/Nogo task during simultaneous EEG/fMRI. Of 38 healthy subjects, 21 subjects reliably showed Nogo-related ICs (Nogo-IC-positive) while 17 subjects (Nogo-IC-negative) did not. Comparing both groups revealed differences on various levels: On trait level, Nogo-IC-negative subjects scored higher on questionnaires regarding attention deficit/hyperactivity disorder; on a behavioral level, they displayed slower response times (RT) and higher intra-individual RT variability while both groups did not differ in their inhibitory performance. On the neurophysiological level, Nogo-IC-negative subjects showed a hyperactivation of left inferior frontal cortex/insula and left putamen as well as significantly reduced P3 amplitudes. Thus, a data-driven approach for IC classification and the resulting presence or absence of early Nogo-specific ICs as criterion for group selection revealed group differences at behavioral and neurophysiological levels. This may indicate electrophysiological phenotypes characterized by inter-individual variations of neural and behavioral correlates of impulse control. We demonstrated that the inter-individual difference in an electrophysiological correlate of response inhibition is correlated with distinct, potentially compensatory neural activity. This may suggest the existence of electrophysiologically dissociable phenotypes of behavioral and neural motor response inhibition with the Nogo-IC-positive phenotype possibly providing

  20. The development of control processes supporting source memory discrimination as revealed by event-related potentials.

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    de Chastelaine, Marianne; Friedman, David; Cycowicz, Yael M

    2007-08-01

    Improvement in source memory performance throughout childhood is thought to be mediated by the development of executive control. As postretrieval control processes may be better time-locked to the recognition response rather than the retrieval cue, the development of processes underlying source memory was investigated with both stimulus- and response-locked event-related potentials (ERPs). These were recorded in children, adolescents, and adults during a recognition memory exclusion task. Green- and red-outlined pictures were studied, but were tested in black outline. The test requirement was to endorse old items shown in one study color ("targets") and to reject new items along with old items shown in the alternative study color ("nontargets"). Source memory improved with age. All age groups retrieved target and nontarget memories as reflected by reliable parietal episodic memory (EM) effects, a stimulus-locked ERP correlate of recollection. Response-locked ERPs to targets and nontargets diverged in all groups prior to the response, although this occurred at an increasingly earlier time point with age. We suggest these findings reflect the implementation of attentional control mechanisms to enhance target memories and facilitate response selection with the greatest and least success, respectively, in adults and children. In adults only, response-locked ERPs revealed an early-onsetting parietal negativity for nontargets, but not for targets. This was suggested to reflect adults' ability to consistently inhibit prepotent target responses for nontargets. The findings support the notion that the development of source memory relies on the maturation of control processes that serve to enhance accurate selection of task-relevant memories.

  1. Automatic generation of predictive dynamic models reveals nuclear phosphorylation as the key Msn2 control mechanism.

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    Sunnåker, Mikael; Zamora-Sillero, Elias; Dechant, Reinhard; Ludwig, Christina; Busetto, Alberto Giovanni; Wagner, Andreas; Stelling, Joerg

    2013-05-28

    Predictive dynamical models are critical for the analysis of complex biological systems. However, methods to systematically develop and discriminate among systems biology models are still lacking. We describe a computational method that incorporates all hypothetical mechanisms about the architecture of a biological system into a single model and automatically generates a set of simpler models compatible with observational data. As a proof of principle, we analyzed the dynamic control of the transcription factor Msn2 in Saccharomyces cerevisiae, specifically the short-term mechanisms mediating the cells' recovery after release from starvation stress. Our method determined that 12 of 192 possible models were compatible with available Msn2 localization data. Iterations between model predictions and rationally designed phosphoproteomics and imaging experiments identified a single-circuit topology with a relative probability of 99% among the 192 models. Model analysis revealed that the coupling of dynamic phenomena in Msn2 phosphorylation and transport could lead to efficient stress response signaling by establishing a rate-of-change sensor. Similar principles could apply to mammalian stress response pathways. Systematic construction of dynamic models may yield detailed insight into nonobvious molecular mechanisms.

  2. Purification of reversibly oxidized proteins (PROP reveals a redox switch controlling p38 MAP kinase activity.

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    Dennis J Templeton

    2010-11-01

    Full Text Available Oxidation of cysteine residues of proteins is emerging as an important means of regulation of signal transduction, particularly of protein kinase function. Tools to detect and quantify cysteine oxidation of proteins have been a limiting factor in understanding the role of cysteine oxidation in signal transduction. As an example, the p38 MAP kinase is activated by several stress-related stimuli that are often accompanied by in vitro generation of hydrogen peroxide. We noted that hydrogen peroxide inhibited p38 activity despite paradoxically increasing the activating phosphorylation of p38. To address the possibility that cysteine oxidation may provide a negative regulatory effect on p38 activity, we developed a biochemical assay to detect reversible cysteine oxidation in intact cells. This procedure, PROP, demonstrated in vivo oxidation of p38 in response to hydrogen peroxide and also to the natural inflammatory lipid prostaglandin J2. Mutagenesis of the potential target cysteines showed that oxidation occurred preferentially on residues near the surface of the p38 molecule. Cysteine oxidation thus controls a functional redox switch regulating the intensity or duration of p38 activity that would not be revealed by immunodetection of phosphoprotein commonly interpreted as reflective of p38 activity.

  3. Redox-controlled backbone dynamics of human cytochrome c revealed by 15N NMR relaxation measurements

    International Nuclear Information System (INIS)

    Sakamoto, Koichi; Kamiya, Masakatsu; Uchida, Takeshi; Kawano, Keiichi; Ishimori, Koichiro

    2010-01-01

    Research highlights: → The dynamic parameters for the backbone dynamics in Cyt c were determined. → The backbone mobility of Cyt c is highly restricted due to the covalently bound heme. → The backbone mobility of Cyt c is more restricted upon the oxidation of the heme. → The redox-dependent dynamics are shown in the backbone of Cyt c. → The backbone dynamics of Cyt c would regulate the electron transfer from Cyt c. -- Abstract: Redox-controlled backbone dynamics in cytochrome c (Cyt c) were revealed by 2D 15 N NMR relaxation experiments. 15 N T 1 and T 2 values and 1 H- 15 N NOEs of uniformly 15 N-labeled reduced and oxidized Cyt c were measured, and the generalized order parameters (S 2 ), the effective correlation time for internal motion (τ e ), the 15 N exchange broadening contributions (R ex ) for each residue, and the overall correlation time (τ m ) were estimated by model-free dynamics formalism. These dynamic parameters clearly showed that the backbone dynamics of Cyt c are highly restricted due to the covalently bound heme that functions as the stable hydrophobic core. Upon oxidation of the heme iron in Cyt c, the average S 2 value was increased from 0.88 ± 0.01 to 0.92 ± 0.01, demonstrating that the mobility of the backbone is further restricted in the oxidized form. Such increases in the S 2 values were more prominent in the loop regions, including amino acid residues near the thioether bonds to the heme moiety and positively charged region around Lys87. Both of the regions are supposed to form the interaction site for cytochrome c oxidase (CcO) and the electron pathway from Cyt c to CcO. The redox-dependent mobility of the backbone in the interaction site for the electron transfer to CcO suggests an electron transfer mechanism regulated by the backbone dynamics in the Cyt c-CcO system.

  4. Power laws reveal phase transitions in landscape controls of fire regimes

    Science.gov (United States)

    Donald McKenzie; Maureen C. Kennedy

    2012-01-01

    Understanding the environmental controls on historical wildfires, and how they changed across spatial scales, is difficult because there are no surviving explicit records of either weather or vegetation (fuels). Here we show how power laws associated with fire-event time series arise in limited domains of parameters that represent critical transitions in the controls...

  5. Proton NMR metabolic profiling of CSF reveals distinct differentiation of meningitis from negative controls.

    Science.gov (United States)

    Chatterji, Tanushri; Singh, Suruchi; Sen, Manodeep; Singh, Ajai Kumar; Agarwal, Gaurav Raj; Singh, Deepak Kumar; Srivastava, Janmejai Kumar; Singh, Alka; Srivastava, Rajeshwar Nath; Roy, Raja

    2017-06-01

    Cerebrospinal fluid (CSF) is an essential bio-fluid of the central nervous system (CNS), playing a vital role in the protection of CNS and performing neuronal function regulation. The chemical composition of CSF varies during onset of meningitis, neurodegenerative disorders (positive controls) and in traumatic cases (negative controls). The study design was broadly categorized into meningitis cases, negative controls and positive controls. Further differentiation among the three groups was carried out using Principal Component Analysis (PCA) followed by supervised Partial Least Square Discriminant Analysis (PLS-DA). The statistical analysis of meningitis vs. negative controls using PLS-DA model resulted in R 2 of 0.97 and Q 2 of 0.85. There was elevation in the levels of ketone bodies, total free amino acids, glutamine, creatine, citrate and choline containing compounds (choline and GPC) in meningitis cases. Similarly, meningitis vs. positive controls resulted in R 2 of 0.80 and Q 2 of 0.60 and showed elevation in the levels of total free amino acids, glutamine, creatine/creatinine and citrate in the meningitis group. Four cases of HIV were identified by PLS-DA model as well as by clinical investigations. On the basis of metabolic profile it was found that negative control CSF samples are more appropriate for differentiation of meningitis than positive control CSF samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Temporal dynamics of motivation-cognitive control interactions revealed by high-resolution pupillometry

    Directory of Open Access Journals (Sweden)

    Kimberly Sarah Chiew

    2013-01-01

    Full Text Available Motivational manipulations, such as the presence of performance-contingent reward incentives, can have substantial influences on cognitive control. Previous evidence suggests that reward incentives may enhance cognitive performance specifically through increased preparatory, or proactive, control processes. The present study examined reward influences on cognitive control dynamics in the AX-Continuous Performance Task (AX-CPT, using high-resolution pupillometry. In the AX-CPT, contextual cues must be actively maintained over a delay in order to appropriately respond to ambiguous target probes. A key feature of the task is that it permits dissociable characterization of preparatory, proactive control processes (i.e., utilization of context and reactive control processes (i.e., target-evoked interference resolution. Task performance profiles suggested that reward incentives enhanced proactive control (context utilization. Critically, pupil dilation was also increased on reward incentive trials during context maintenance periods, suggesting trial-specific shifts in proactive control, particularly when context cues indicated the need to overcome the dominant target response bias. Reward incentives had both transient (i.e., trial-by-trial and sustained (i.e., block-based effects on pupil dilation, which may reflect distinct underlying processes. The transient pupillary effects were present even when comparing against trials matched in task performance, suggesting a unique motivational influence of reward incentives. These results suggest that pupillometry may be a useful technique for investigating reward motivational signals and their dynamic influence on cognitive control.

  7. (No) Time for control: Frontal theta dynamics reveal the cost of temporally guided conflict anticipation

    NARCIS (Netherlands)

    van Driel, J.; Swart, J.C.; Egner, T.; Ridderinkhof, K.R.; Cohen, M.

    2015-01-01

    During situations of response conflict, cognitive control is characterized by prefrontal theta-band (3- to 8-Hz) activity. It has been shown that cognitive control can be triggered proactively by contextual cues that predict conflict. Here, we investigated whether a pretrial preparation interval

  8. (No) time for control: frontal theta dynamics reveal the cost of temporally guided conflict anticipation

    NARCIS (Netherlands)

    van Driel, J.; Swart, J.C.; Egner, T.; Ridderinkhof, K.R.; Cohen, M.X.

    2015-01-01

    During situations of response conflict, cognitive control is characterized by prefrontal theta-band (3- to 8-Hz) activity. It has been shown that cognitive control can be triggered proactively by contextual cues that predict conflict. Here, we investigated whether a pretrial preparation interval

  9. Noise Response Data Reveal Novel Controllability Gramian for Nonlinear Network Dynamics

    Science.gov (United States)

    Kashima, Kenji

    2016-01-01

    Control of nonlinear large-scale dynamical networks, e.g., collective behavior of agents interacting via a scale-free connection topology, is a central problem in many scientific and engineering fields. For the linear version of this problem, the so-called controllability Gramian has played an important role to quantify how effectively the dynamical states are reachable by a suitable driving input. In this paper, we first extend the notion of the controllability Gramian to nonlinear dynamics in terms of the Gibbs distribution. Next, we show that, when the networks are open to environmental noise, the newly defined Gramian is equal to the covariance matrix associated with randomly excited, but uncontrolled, dynamical state trajectories. This fact theoretically justifies a simple Monte Carlo simulation that can extract effectively controllable subdynamics in nonlinear complex networks. In addition, the result provides a novel insight into the relationship between controllability and statistical mechanics. PMID:27264780

  10. Transparency Trade-offs for a 3-channel Controller Revealed by the Bounded Environment Passivity Method

    OpenAIRE

    Willaert, Bert; Corteville, Brecht; Reynaerts, Dominiek; Van Brussel, Hendrik; Vander Poorten, Emmanuel

    2010-01-01

    In this paper, the Bounded Environment Passivity method [1] is applied to a 3-channel controller. This method enables the design of teleoperation controllers that show passive behaviour for interactions with a bounded range of environments. The resulting tuning guidelines, derived analytically, provide interesting tuning flexibility, which allows to focus on different aspects of transparency. As telesurgery is the motivation behind this work, the focus lies on correctly r...

  11. Fronto-parietal network oscillations reveal relationship between working memory capacity and cognitive control

    Directory of Open Access Journals (Sweden)

    Rasa eGulbinaite

    2014-09-01

    Full Text Available Executive-attention theory proposes a close relationship between working memory capacity (WMC and cognitive control abilities. However, conflicting results are documented in the literature, with some studies reporting that individual variations in WMC predict differences in cognitive control and trial-to-trial control adjustments (operationalized as the size of the congruency effect and congruency sequence effects, respectively, while others report no WMC-related differences. We hypothesized that brain network dynamics might be a more sensitive measure of WMC-related differences in cognitive control abilities. Thus, in the present study, we measured human EEG during the Simon task to characterize WMC-related differences in the neural dynamics of conflict processing and adaptation to conflict. Although high- and low-WMC individuals did not differ behaviorally, there were substantial WMC-related differences in theta (4-8 Hz and delta (1-3 Hz connectivity in fronto-parietal networks. Group differences in local theta and delta power were relatively less pronounced. These results suggest that the relationship between WMC and cognitive control abilities is more strongly reflected in large-scale oscillatory network dynamics than in spatially localized activity or in behavioral task performance.

  12. Merging metagenomics and geochemistry reveals environmental controls on biological diversity and evolution.

    Science.gov (United States)

    Alsop, Eric B; Boyd, Eric S; Raymond, Jason

    2014-05-28

    The metabolic strategies employed by microbes inhabiting natural systems are, in large part, dictated by the physical and geochemical properties of the environment. This study sheds light onto the complex relationship between biology and environmental geochemistry using forty-three metagenomes collected from geochemically diverse and globally distributed natural systems. It is widely hypothesized that many uncommonly measured geochemical parameters affect community dynamics and this study leverages the development and application of multidimensional biogeochemical metrics to study correlations between geochemistry and microbial ecology. Analysis techniques such as a Markov cluster-based measure of the evolutionary distance between whole communities and a principal component analysis (PCA) of the geochemical gradients between environments allows for the determination of correlations between microbial community dynamics and environmental geochemistry and provides insight into which geochemical parameters most strongly influence microbial biodiversity. By progressively building from samples taken along well defined geochemical gradients to samples widely dispersed in geochemical space this study reveals strong links between the extent of taxonomic and functional diversification of resident communities and environmental geochemistry and reveals temperature and pH as the primary factors that have shaped the evolution of these communities. Moreover, the inclusion of extensive geochemical data into analyses reveals new links between geochemical parameters (e.g. oxygen and trace element availability) and the distribution and taxonomic diversification of communities at the functional level. Further, an overall geochemical gradient (from multivariate analyses) between natural systems provides one of the most complete predictions of microbial taxonomic and functional composition. Clustering based on the frequency in which orthologous proteins occur among metagenomes

  13. A Genome-wide multidimensional RNAi screen reveals pathways controlling MHC class II antigen presentation

    NARCIS (Netherlands)

    Paul, Petra; van den Hoorn, Tineke; Jongsma, Marlieke L. M.; Bakker, Mark J.; Hengeveld, Rutger; Janssen, Lennert; Cresswell, Peter; Egan, David A.; van Ham, Marieke; ten Brinke, Anja; Ovaa, Huib; Beijersbergen, Roderick L.; Kuijl, Coenraad; Neefjes, Jacques

    2011-01-01

    MHC class II molecules (MHC-II) present peptides to T helper cells to facilitate immune responses and are strongly linked to autoimmune diseases. To unravel processes controlling MHC-II antigen presentation, we performed a genome-wide flow cytometry-based RNAi screen detecting MHC-II expression and

  14. A Landscape of Therapeutic Cooperativity in KRAS Mutant Cancers Reveals Principles for Controlling Tumor Evolution

    Directory of Open Access Journals (Sweden)

    Grace R. Anderson

    2017-07-01

    Full Text Available Combinatorial inhibition of effector and feedback pathways is a promising treatment strategy for KRAS mutant cancers. However, the particular pathways that should be targeted to optimize therapeutic responses are unclear. Using CRISPR/Cas9, we systematically mapped the pathways whose inhibition cooperates with drugs targeting the KRAS effectors MEK, ERK, and PI3K. By performing 70 screens in models of KRAS mutant colorectal, lung, ovarian, and pancreas cancers, we uncovered universal and tissue-specific sensitizing combinations involving inhibitors of cell cycle, metabolism, growth signaling, chromatin regulation, and transcription. Furthermore, these screens revealed secondary genetic modifiers of sensitivity, yielding a SRC inhibitor-based combination therapy for KRAS/PIK3CA double-mutant colorectal cancers (CRCs with clinical potential. Surprisingly, acquired resistance to combinations of growth signaling pathway inhibitors develops rapidly following treatment, but by targeting signaling feedback or apoptotic priming, it is possible to construct three-drug combinations that greatly delay its emergence.

  15. Unifying model of shoot gravitropism reveals proprioception as a central feature of posture control in plants

    DEFF Research Database (Denmark)

    Bastien, Renaud; Bohr, Tomas; Moulia, Bruno

    2012-01-01

    Gravitropism, the slow reorientation of plant growth in response to gravity, is a key determinant of the form and posture of land plants. Shoot gravitropism is triggered when statocysts sense the local angle of the growing organ relative to the gravitational field. Lateral transport of the hormone...... is thus as important as gravisensing in gravitropic control, and the B ratio can be measured as phenotype in genetic studies....

  16. What does distractibility in ADHD reveal about mechanisms for top-down attentional control?

    OpenAIRE

    Friedman-Hill, Stacia R.; Wagman, Meryl R.; Gex, Saskia E.; Pine, Daniel S.; Leibenluft, Ellen; Ungerleider, Leslie G.

    2010-01-01

    In this study, we attempted to clarify whether distractibility in ADHD might arise from increased sensory-driven interference or from inefficient top-down control. We employed an attentional filtering paradigm in which discrimination difficulty and distractor salience (amount of image “graying”) were parametrically manipulated. Increased discrimination difficulty should add to the load of top-down processes, whereas increased distractor salience should produce stronger sensory interference. W...

  17. Confirmatory factor analysis reveals a latent cognitive structure common to bipolar disorder, schizophrenia, and normal controls.

    Science.gov (United States)

    Schretlen, David J; Peña, Javier; Aretouli, Eleni; Orue, Izaskun; Cascella, Nicola G; Pearlson, Godfrey D; Ojeda, Natalia

    2013-06-01

    We sought to determine whether a single hypothesized latent factor structure would characterize cognitive functioning in three distinct groups. We assessed 576 adults (340 community controls, 126 adults with bipolar disorder, and 110 adults with schizophrenia) using 15 measures derived from nine cognitive tests. Confirmatory factor analysis (CFA) was conducted to examine the fit of a hypothesized six-factor model. The hypothesized factors included attention, psychomotor speed, verbal memory, visual memory, ideational fluency, and executive functioning. The six-factor model provided an excellent fit for all three groups [for community controls, root mean square error of approximation (RMSEA) schizophrenia, RMSEA = 0.06 and CFI = 0.98]. Alternate models that combined fluency with processing speed or verbal and visual memory reduced the goodness of fit. Multi-group CFA results supported factor invariance across the three groups. Confirmatory factor analysis supported a single six-factor structure of cognitive functioning among patients with schizophrenia or bipolar disorder and community controls. While the three groups clearly differ in level of performance, they share a common underlying architecture of information processing abilities. These cognitive factors could provide useful targets for clinical trials of treatments that aim to enhance information processing in persons with neurological and neuropsychiatric disorders. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. The Him gene reveals a balance of inputs controlling muscle differentiation in Drosophila.

    Science.gov (United States)

    Liotta, David; Han, Jun; Elgar, Stuart; Garvey, Clare; Han, Zhe; Taylor, Michael V

    2007-08-21

    Tissue development requires the controlled regulation of cell-differentiation programs. In muscle, the Mef2 transcription factor binds to and activates the expression of many genes and has a major positive role in the orchestration of differentiation. However, little is known about how Mef2 activity is regulated in vivo during development. Here, we characterize a gene, Holes in muscle (Him), which our results indicate is part of this control in Drosophila. Him expression rapidly declines as embryonic muscle differentiates, and consistent with this, Him overexpression inhibits muscle differentiation. This inhibitory effect is suppressed by mef2, implicating Him in the mef2 pathway. We then found that Him downregulates the transcriptional activity of Mef2 in both cell culture and in vivo. Furthermore, Him protein binds Groucho, a conserved, transcriptional corepressor, through a WRPW motif and requires this motif and groucho function to inhibit both muscle differentiation and Mef2 activity during development. Together, our results identify a mechanism that can inhibit muscle differentiation in vivo. We conclude that a balance of positive and negative inputs, including Mef2, Him, and Groucho, controls muscle differentiation during Drosophila development and suggest that one outcome is to hold developing muscle cells in a state with differentiation genes poised to be expressed.

  19. Phylogenomics Controlling for Base Compositional Bias Reveals a Single Origin of Eusociality in Corbiculate Bees.

    Science.gov (United States)

    Romiguier, Jonathan; Cameron, Sydney A; Woodard, S Hollis; Fischman, Brielle J; Keller, Laurent; Praz, Christophe J

    2016-03-01

    As increasingly large molecular data sets are collected for phylogenomics, the conflicting phylogenetic signal among gene trees poses challenges to resolve some difficult nodes of the Tree of Life. Among these nodes, the phylogenetic position of the honey bees (Apini) within the corbiculate bee group remains controversial, despite its considerable importance for understanding the emergence and maintenance of eusociality. Here, we show that this controversy stems in part from pervasive phylogenetic conflicts among GC-rich gene trees. GC-rich genes typically have a high nucleotidic heterogeneity among species, which can induce topological conflicts among gene trees. When retaining only the most GC-homogeneous genes or using a nonhomogeneous model of sequence evolution, our analyses reveal a monophyletic group of the three lineages with a eusocial lifestyle (honey bees, bumble bees, and stingless bees). These phylogenetic relationships strongly suggest a single origin of eusociality in the corbiculate bees, with no reversal to solitary living in this group. To accurately reconstruct other important evolutionary steps across the Tree of Life, we suggest removing GC-rich and GC-heterogeneous genes from large phylogenomic data sets. Interpreted as a consequence of genome-wide variations in recombination rates, this GC effect can affect all taxa featuring GC-biased gene conversion, which is common in eukaryotes. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. (No) time for control: Frontal theta dynamics reveal the cost of temporally guided conflict anticipation.

    Science.gov (United States)

    van Driel, Joram; Swart, Jennifer C; Egner, Tobias; Ridderinkhof, K Richard; Cohen, Michael X

    2015-12-01

    During situations of response conflict, cognitive control is characterized by prefrontal theta-band (3- to 8-Hz) activity. It has been shown that cognitive control can be triggered proactively by contextual cues that predict conflict. Here, we investigated whether a pretrial preparation interval could serve as such a cue. This would show that the temporal contingencies embedded in the task can be used to anticipate upcoming conflict. To this end, we recorded electroencephalography (EEG) from 30 human subjects while they performed a version of a Simon task in which the duration of a fixation cross between trials predicted whether the next trial would contain response conflict. Both their behavior and EEG activity showed a consistent but unexpected pattern of results: The conflict effect (increased reaction times and decreased accuracy on conflict as compared to nonconflict trials) was stronger when conflict was cued, and this was associated with stronger conflict-related midfrontal theta activity and functional connectivity. Interestingly, intervals that predicted conflict did show a pretarget increase in midfrontal theta power. These findings suggest that temporally guided expectations of conflict do heighten conflict anticipation, but also lead to less efficiently applied reactive control. We further explored this post-hoc interpretation by means of three behavioral follow-up experiments, in which we used nontemporal cues, semantically informative cues, and neutral cues. Together, this body of results suggests that the counterintuitive cost of conflict cueing may not be uniquely related to the temporal domain, but may instead be related to the implicitness and validity of the cue.

  1. Ground-based infrared surveys: imaging the thermal fields at volcanoes and revealing the controlling parameters.

    Science.gov (United States)

    Pantaleo, Michele; Walter, Thomas

    2013-04-01

    Temperature monitoring is a widespread procedure in the frame of volcano hazard monitoring. Indeed temperature changes are expected to reflect changes in volcanic activity. We propose a new approach, within the thermal monitoring, which is meant to shed light on the parameters controlling the fluid pathways and the fumarole sites by using infrared measurements. Ground-based infrared cameras allow one to remotely image the spatial distribution, geometric pattern and amplitude of fumarole fields on volcanoes at metre to centimetre resolution. Infrared mosaics and time series are generated and interpreted, by integrating geological field observations and modeling, to define the setting of the volcanic degassing system at shallow level. We present results for different volcano morphologies and show that lithology, structures and topography control the appearance of fumarole field by the creation of permeability contrasts. We also show that the relative importance of those parameters is site-dependent. Deciphering the setting of the degassing system is essential for hazard assessment studies because it would improve our understanding on how the system responds to endogenous or exogenous modification.

  2. Cortical processes associated with continuous balance control as revealed by EEG spectral power.

    Science.gov (United States)

    Hülsdünker, T; Mierau, A; Neeb, C; Kleinöder, H; Strüder, H K

    2015-04-10

    Balance is a crucial component in numerous every day activities such as locomotion. Previous research has reported distinct changes in cortical theta activity during transient balance instability. However, there remains little understanding of the neural mechanisms underlying continuous balance control. This study aimed to investigate cortical theta activity during varying difficulties of continuous balance tasks, as well as examining the relationship between theta activity and balance performance. 37 subjects completed nine balance tasks with different levels of surface stability and base of support. Throughout the balancing task, electroencephalogram (EEG) was recorded from 32 scalp locations. ICA-based artifact rejection was applied and spectral power was analyzed in the theta frequency band. Theta power increased in the frontal, central, and parietal regions of the cortex when balance tasks became more challenging. In addition, fronto-central and centro-parietal theta power correlated with balance performance. This study demonstrates the involvement of the cerebral cortex in maintaining upright posture during continuous balance tasks. Specifically, the results emphasize the important role of frontal and parietal theta oscillations in balance control. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Association mapping in sunflower (Helianthus annuus L.) reveals independent control of apical vs. basal branching.

    Science.gov (United States)

    Nambeesan, Savithri U; Mandel, Jennifer R; Bowers, John E; Marek, Laura F; Ebert, Daniel; Corbi, Jonathan; Rieseberg, Loren H; Knapp, Steven J; Burke, John M

    2015-03-11

    Shoot branching is an important determinant of plant architecture and influences various aspects of growth and development. Selection on branching has also played an important role in the domestication of crop plants, including sunflower (Helianthus annuus L.). Here, we describe an investigation of the genetic basis of variation in branching in sunflower via association mapping in a diverse collection of cultivated sunflower lines. Detailed phenotypic analyses revealed extensive variation in the extent and type of branching within the focal population. After correcting for population structure and kinship, association analyses were performed using a genome-wide collection of SNPs to identify genomic regions that influence a variety of branching-related traits. This work resulted in the identification of multiple previously unidentified genomic regions that contribute to variation in branching. Genomic regions that were associated with apical and mid-apical branching were generally distinct from those associated with basal and mid-basal branching. Homologs of known branching genes from other study systems (i.e., Arabidopsis, rice, pea, and petunia) were also identified from the draft assembly of the sunflower genome and their map positions were compared to those of associations identified herein. Numerous candidate branching genes were found to map in close proximity to significant branching associations. In sunflower, variation in branching is genetically complex and overall branching patterns (i.e., apical vs. basal) were found to be influenced by distinct genomic regions. Moreover, numerous candidate branching genes mapped in close proximity to significant branching associations. Although the sunflower genome exhibits localized islands of elevated linkage disequilibrium (LD), these non-random associations are known to decay rapidly elsewhere. The subset of candidate genes that co-localized with significant associations in regions of low LD represents the most

  4. High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model.

    Directory of Open Access Journals (Sweden)

    Chiao-Ling Lo

    2016-08-01

    Full Text Available Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP. This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross resulted in small haplotype blocks (HB with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS, were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50% of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284 and intronic regions (169 with the least in exon's (4, suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a, excitatory receptors (Grin2a, Gria3, Grip1, neurotransmitters (Pomc, and synapses (Snap29. This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits.

  5. High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model.

    Science.gov (United States)

    Lo, Chiao-Ling; Lossie, Amy C; Liang, Tiebing; Liu, Yunlong; Xuei, Xiaoling; Lumeng, Lawrence; Zhou, Feng C; Muir, William M

    2016-08-01

    Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder) in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP). This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross) resulted in small haplotype blocks (HB) with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate) to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS), were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50%) of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284) and intronic regions (169) with the least in exon's (4), suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a), excitatory receptors (Grin2a, Gria3, Grip1), neurotransmitters (Pomc), and synapses (Snap29). This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits.

  6. Revealing Hidden Structural Order Controlling Both Fast and Slow Glassy Dynamics in Supercooled Liquids

    Directory of Open Access Journals (Sweden)

    Hua Tong

    2018-03-01

    Full Text Available The dynamics of a supercooled liquid near the glass transition is characterized by two-step relaxation, fast β and slow α relaxations. Because of the apparently disordered nature of glassy structures, there have been long debates over whether the origin of drastic slowing-down of the α relaxation accompanied by heterogeneous dynamics is thermodynamic or dynamic. Furthermore, it has been elusive whether there is any deep connection between fast β and slow α modes. To settle these issues, here we introduce a set of new structural order parameters characterizing sterically favored structures with high local packing capability, and then access structure-dynamics correlation by a novel nonlocal approach. We find that the particle mobility is under control of the static order parameter field. The fast β process is controlled by the instantaneous order parameter field locally, resulting in short-time particle-scale dynamics. Then the mobility field progressively develops with time t, following the initial order parameter field from disorder to more ordered regions. As is well known, the heterogeneity in the mobility field (dynamic heterogeneity is maximized with a characteristic length ξ_{4}, when t reaches the relaxation time τ_{α}. We discover that this mobility pattern can be predicted solely by a spatial coarse graining of the initial order parameter field at t=0 over a length ξ without any dynamical information. Furthermore, we find a relation ξ∼ξ_{4}, indicating that the static length ξ grows coherently with the dynamic one ξ_{4} upon cooling. This further suggests an intrinsic link between τ_{α} and ξ: the growth of the static length ξ is the origin of dynamical slowing-down. These we confirm for the first time in binary glass formers both in two and three spatial dimensions. Thus, a static structure has two intrinsic characteristic lengths, particle size and ξ, which control dynamics in local and nonlocal manners, resulting

  7. Revealing Hidden Structural Order Controlling Both Fast and Slow Glassy Dynamics in Supercooled Liquids

    Science.gov (United States)

    Tong, Hua; Tanaka, Hajime

    2018-01-01

    The dynamics of a supercooled liquid near the glass transition is characterized by two-step relaxation, fast β and slow α relaxations. Because of the apparently disordered nature of glassy structures, there have been long debates over whether the origin of drastic slowing-down of the α relaxation accompanied by heterogeneous dynamics is thermodynamic or dynamic. Furthermore, it has been elusive whether there is any deep connection between fast β and slow α modes. To settle these issues, here we introduce a set of new structural order parameters characterizing sterically favored structures with high local packing capability, and then access structure-dynamics correlation by a novel nonlocal approach. We find that the particle mobility is under control of the static order parameter field. The fast β process is controlled by the instantaneous order parameter field locally, resulting in short-time particle-scale dynamics. Then the mobility field progressively develops with time t , following the initial order parameter field from disorder to more ordered regions. As is well known, the heterogeneity in the mobility field (dynamic heterogeneity) is maximized with a characteristic length ξ4, when t reaches the relaxation time τα. We discover that this mobility pattern can be predicted solely by a spatial coarse graining of the initial order parameter field at t =0 over a length ξ without any dynamical information. Furthermore, we find a relation ξ ˜ξ4, indicating that the static length ξ grows coherently with the dynamic one ξ4 upon cooling. This further suggests an intrinsic link between τα and ξ : the growth of the static length ξ is the origin of dynamical slowing-down. These we confirm for the first time in binary glass formers both in two and three spatial dimensions. Thus, a static structure has two intrinsic characteristic lengths, particle size and ξ , which control dynamics in local and nonlocal manners, resulting in the emergence of the two

  8. Synthesis of Isomeric Phosphoubiquitin Chains Reveals that Phosphorylation Controls Deubiquitinase Activity and Specificity

    Directory of Open Access Journals (Sweden)

    Nicolas Huguenin-Dezot

    2016-07-01

    Full Text Available Ubiquitin is post-translationally modified by phosphorylation at several sites, but the consequences of these modifications are largely unknown. Here, we synthesize multi-milligram quantities of ubiquitin phosphorylated at serine 20, serine 57, and serine 65 via genetic code expansion. We use these phosphoubiquitins for the enzymatic assembly of 20 isomeric phosphoubiquitin dimers, with different sites of isopeptide linkage and/or phosphorylation. We discover that phosphorylation of serine 20 on ubiquitin converts UBE3C from a dual-specificity E3 ligase into a ligase that primarily synthesizes K48 chains. We profile the activity of 31 deubiquitinases on the isomeric phosphoubiquitin dimers in 837 reactions, and we discover that phosphorylation at distinct sites in ubiquitin can activate or repress cleavage of a particular linkage by deubiquitinases and that phosphorylation at a single site in ubiquitin can control the specificity of deubiquitinases for distinct ubiquitin linkages.

  9. Dominant hemisphere lateralization of cortical parasympathetic control as revealed by frontotemporal dementia

    Science.gov (United States)

    Guo, Christine C.; Sturm, Virginia E.; Zhou, Juan; Gennatas, Efstathios D.; Trujillo, Andrew J.; Hua, Alice Y.; Crawford, Richard; Stables, Lara; Kramer, Joel H.; Rankin, Katherine; Levenson, Robert W.; Rosen, Howard J.; Miller, Bruce L.; Seeley, William W.

    2016-01-01

    The brain continuously influences and perceives the physiological condition of the body. Related cortical representations have been proposed to shape emotional experience and guide behavior. Although previous studies have identified brain regions recruited during autonomic processing, neurological lesion studies have yet to delineate the regions critical for maintaining autonomic outflow. Even greater controversy surrounds hemispheric lateralization along the parasympathetic–sympathetic axis. The behavioral variant of frontotemporal dementia (bvFTD), featuring progressive and often asymmetric degeneration that includes the frontoinsular and cingulate cortices, provides a unique lesion model for elucidating brain structures that control autonomic tone. Here, we show that bvFTD is associated with reduced baseline cardiac vagal tone and that this reduction correlates with left-lateralized functional and structural frontoinsular and cingulate cortex deficits and with reduced agreeableness. Our results suggest that networked brain regions in the dominant hemisphere are critical for maintaining an adaptive level of baseline parasympathetic outflow. PMID:27071080

  10. Pump-shaped dump optimal control reveals the nuclear reaction pathway of isomerization of a photoexcited cyanine dye.

    Science.gov (United States)

    Dietzek, Benjamin; Brüggemann, Ben; Pascher, Torbjörn; Yartsev, Arkady

    2007-10-31

    Using optimal control as a spectroscopic tool we decipher the details of the molecular dynamics of the essential multidimensional excited-state photoisomerization - a fundamental chemical reaction of key importance in biology. Two distinct nuclear motions are identified in addition to the overall bond-twisting motion: Initially, the reaction is dominated by motion perpendicular to the torsion coordinate. At later times, a second optically active vibration drives the system along the reaction path to the bottom of the excited-state potential. The time scales of the wavepacket motion on a different part of the excited-state potential are detailed by pump-shaped dump optimal control. This technique offers new means to control a chemical reaction far from the Franck-Condon point of absorption and to map details of excited-state reaction pathways revealing unique insights into the underlying reaction mechanism.

  11. Torque controlled rotary-shear experiments reveal pseudotachilites formation-dynamics and precursor events

    Science.gov (United States)

    Tisato, Nicola; Cordonnier, Benoit; De Siena, Luca; Lavier, Luc; Di Toro, Giulio

    2017-04-01

    Except few cases, rotary shear tests, which are designed to study dynamic friction and strengthening/weakening mechanisms in seismogenic faults, are performed by imposing, to the specimens, a slipping velocity that is pre-defined. This approach has been adopted from engineering that typically, tests man-made objects that, when functioning, spin or slide at a pre-defined velocity under a pre-defined load. On the other hand, natural earthquakes are the effect of a rupture that nucleates, propagates and arrests in the subsurface. These three phases, and the consequent emerging fault slipping velocity, are controlled by the accumulated and released energy around the seismogenic fault before, during and after the earthquake. Thus, imposing the slipping velocity in laboratory experiments might not represent the best option to uncover many aspects of earthquake nucleation and fault slipping dynamics. Here we present some experiments performed with an innovative rotary shear apparatus that uses a clock-spring that when winded provides to the rotating sample a linearly increasing torque. Thus, the nucleation of simulated events occur spontaneously when the shear stress on the slipping surface overcomes the static friction times the normal load that is controlled by a deadweight. In addition, this method allows studying precursory seismic events resembling natural slow-slip earthquakes. We report some preliminary results for a transparent polymer that has melting point 340 K and allows observing the slipping surface (i.e., the contact between the two samples). By coupling: i) the rotary shear apparatus, ii) a video camera recording at 60 fps and a iii) laser pointer we observed the formation and evolution of a melt film that forms in the slipping surface after a phase of "dry" stick-slip. After each seismic event the melt layer solidify forming a pseudotachilite that partially welds the slipping surfaces. We also present the mechanical data that show rupture strengthening in

  12. New inducible genetic method reveals critical roles of GABA in the control of feeding and metabolism.

    Science.gov (United States)

    Meng, Fantao; Han, Yong; Srisai, Dollada; Belakhov, Valery; Farias, Monica; Xu, Yong; Palmiter, Richard D; Baasov, Timor; Wu, Qi

    2016-03-29

    Currently available inducible Cre/loxP systems, despite their considerable utility in gene manipulation, have pitfalls in certain scenarios, such as unsatisfactory recombination rates and deleterious effects on physiology and behavior. To overcome these limitations, we designed a new, inducible gene-targeting system by introducing an in-frame nonsense mutation into the coding sequence of Cre recombinase (nsCre). Mutant mRNAs transcribed from nsCre transgene can be efficiently translated into full-length, functional Cre recombinase in the presence of nonsense suppressors such as aminoglycosides. In a proof-of-concept model, GABA signaling from hypothalamic neurons expressing agouti-related peptide (AgRP) was genetically inactivated within 4 d after treatment with a synthetic aminoglycoside. Disruption of GABA synthesis in AgRP neurons in young adult mice led to a dramatic loss of body weight due to reduced food intake and elevated energy expenditure; they also manifested glucose intolerance. In contrast, older mice with genetic inactivation of GABA signaling by AgRP neurons had only transient reduction of feeding and body weight; their energy expenditure and glucose tolerance were unaffected. These results indicate that GABAergic signaling from AgRP neurons plays a key role in the control of feeding and metabolism through an age-dependent mechanism. This new genetic technique will augment current tools used to elucidate mechanisms underlying many physiological and neurological processes.

  13. Dynamic Modeling of GAIT System Reveals Transcriptome Expansion and Translational Trickle Control Device

    Science.gov (United States)

    Yao, Peng; Potdar, Alka A.; Arif, Abul; Ray, Partho Sarothi; Mukhopadhyay, Rupak; Willard, Belinda; Xu, Yichi; Yan, Jun; Saidel, Gerald M.; Fox, Paul L.

    2012-01-01

    SUMMARY Post-transcriptional regulatory mechanisms superimpose “fine-tuning” control upon “on-off” switches characteristic of gene transcription. We have exploited computational modeling with experimental validation to resolve an anomalous relationship between mRNA expression and protein synthesis. Differential GAIT (Gamma-interferon Activated Inhibitor of Translation) complex activation repressed VEGF-A synthesis to a low, constant rate despite high, variable VEGFA mRNA expression. Dynamic model simulations indicated the presence of an unidentified, inhibitory GAIT element-interacting factor. We discovered a truncated form of glutamyl-prolyl tRNA synthetase (EPRS), the GAIT constituent that binds the 3’-UTR GAIT element in target transcripts. The truncated protein, EPRSN1, prevents binding of functional GAIT complex. EPRSN1 mRNA is generated by a remarkable polyadenylation-directed conversion of a Tyr codon in the EPRS coding sequence to a stop codon (PAY*). By low-level protection of GAIT element-bearing transcripts, EPRSN1 imposes a robust “translational trickle” of target protein expression. Genome-wide analysis shows PAY* generates multiple truncated transcripts thereby contributing to transcriptome expansion. PMID:22386318

  14. A randomized controlled design reveals barriers to citizenship for low-income immigrants.

    Science.gov (United States)

    Hainmueller, Jens; Lawrence, Duncan; Gest, Justin; Hotard, Michael; Koslowski, Rey; Laitin, David D

    2018-01-30

    Citizenship endows legal protections and is associated with economic and social gains for immigrants and their communities. In the United States, however, naturalization rates are relatively low. Yet we lack reliable knowledge as to what constrains immigrants from applying. Drawing on data from a public/private naturalization program in New York, this research provides a randomized controlled study of policy interventions that address these constraints. The study tested two programmatic interventions among low-income immigrants who are eligible for citizenship. The first randomly assigned a voucher that covers the naturalization application fee among immigrants who otherwise would have to pay the full cost of the fee. The second randomly assigned a set of behavioral nudges, similar to outreach efforts used by service providers, among immigrants whose incomes were low enough to qualify them for a federal waiver that eliminates the application fee. Offering the fee voucher increased naturalization application rates by about 41%, suggesting that application fees act as a barrier for low-income immigrants who want to become US citizens. The nudges to encourage the very poor to apply had no discernible effect, indicating the presence of nonfinancial barriers to naturalization. Copyright © 2018 the Author(s). Published by PNAS.

  15. Ca isotopes reveal weak control of tectonic uplift on long-term climate change

    Science.gov (United States)

    Moore, J.; Jacobson, A. D.; Holmden, C. E.; Craw, D.

    2010-12-01

    , which are longer on the eastern side of the main divide. After correcting for this input, we apportion Ca in all rivers to silicate versus carbonate weathering using a two-component mixing equation. For non-glaciated streams, the δ44/40Ca method and a conventional Ca/Na method agree within 2%. Silicate weathering contributes less Ca west of the main divide where uplift rates are highest. For actively glaciated catchments, the δ44/40Ca method attributes 26% more Ca to silicate weathering than the Ca/Na method. We ascribe this difference to non-stoichiometric leaching of Ca from freshly cleaved rock surfaces. This reaction must occur even faster than carbonate weathering, which dominates in adjacent non-glaciated watersheds. Our results support the assertion that mountain uplift does not dramatically elevate long-term atmospheric CO2 consumption rates compared to tectonically stable landscapes. However, δ44/40Ca reveals that glaciation, which is genetically linked to mountain uplift, yields moderately higher CO2 consumption rates than previously realized. Additionally, our study highlights how biological processes can influence the terrestrial Ca cycle.

  16. Sexual dimorphism in white campion: complex control of carpel number is revealed by Y chromosome deletions

    International Nuclear Information System (INIS)

    Lardon, A.; Georgiev, S.; Aghmir, A.; Le Merrer, G.; Negrutiu, I.

    1999-01-01

    Sexual dimorphism in the dioecious plant white campion (Silene latifolia = Melandrium album) is under the control of two main regions on the Y chromosome. One such region, encoding the gynoecium-suppressing function (GSF), is responsible for the arrest of carpel initiation in male flowers. To generate chromosomal deletions, we used pollen irradiation in male plants to produce hermaphroditic mutants (bsx mutants) in which carpel development was restored. The mutants resulted from alterations in at least two GSF chromosomal regions, one autosomal and one located on the distal half of the (p)-arm of the Y chromosome. The two mutations affected carpel development independently, each mutation showing incomplete penetrance and variegation, albeit at significantly different levels. During successive meiotic generations, a progressive increase in penetrance and a reduction in variegation levels were observed and quantified at the level of the Y-linked GSF (GSF-Y). Possible mechanisms are proposed to explain the behavior of the bsx mutations: epigenetic regulation or/and second-site mutation of modifier genes. In addition, studies on the inheritance of the hermaphroditic trait showed that, unlike wild-type Y chromosomes, deleted Y chromosomes can be transmitted through both the male and the female lines. Altogether, these findings bring experimental support, on the one hand, to the existence on the Y chromosome of genic meiotic drive function(s) and, on the other hand, to models that consider that dioecy evolved through multiple mutation events. As such, the GSF is actually a system containing more than one locus and whose primary component is located on the Y chromosome

  17. Theoretical Insights Reveal Novel Motions in Csk's SH3 Domain That Control Kinase Activation.

    Directory of Open Access Journals (Sweden)

    Sulyman Barkho

    Full Text Available The Src family of tyrosine kinases (SFKs regulate numerous aspects of cell growth and differentiation and are under the principal control of the C-terminal Src Kinase (Csk. Although Csk and SFKs share conserved kinase, SH2 and SH3 domains, they differ considerably in three-dimensional structure, regulatory mechanism, and the intrinsic kinase activities. Although the SH2 and SH3 domains are known to up- or down-regulate tyrosine kinase function, little is known about the global motions in the full-length kinase that govern these catalytic variations. We use a combination of accelerated Molecular Dynamics (aMD simulations and experimental methods to provide a new view of functional motions in the Csk scaffold. These computational studies suggest that high frequency vibrations in the SH2 domain are coupled through the N-terminal lobe of the kinase domain to motions in the SH3 domain. The effects of these reflexive movements on the kinase domain can be viewed using both Deuterium Exchange Mass Spectrometry (DXMS and steady-state kinetic methods. Removal of several contacts, including a crystallographically unobserved N-terminal segment, between the SH3 and kinase domains short-circuit these coupled motions leading to reduced catalytic efficiency and stability of N-lobe motifs within the kinase domain. The data expands the model of Csk's activation whereby separate domains productively interact with two diametrically opposed surfaces of the kinase domain. Such reversible transitions may organize the active structure of the tyrosine kinase domain of Csk.

  18. Controls on slow-moving landslides revealed by satellite and airborne InSAR

    Science.gov (United States)

    Handwerger, Alexander L.; Fielding, Eric J.

    2017-04-01

    Landslides display a wide variety of behaviors ranging from slow persistent motion to rapid acceleration and catastrophic failure. Given the variety of possible behaviors, improvements to our understanding of landslide mechanics are critical for accurate predictions of landslide dynamics. To better constrain the mechanisms that control landslide motion, we use recent SAR data collected by Copernicus Sentinel-1A/B, NASA UAVSAR, JAXA ALOS-2, and DLR TerraSAR-X to quantify the time-dependent kinematics of over 200 slow-moving landslides in the Central and Northern California Coast Ranges. These landslides are ideally suited for InSAR investigations due to their size (up to 5 km in length and 0.5 km in width), persistent downslope motion with low velocities (m/yr), and sparse vegetation. We quantify the seasonal and multi-year changes in velocity driven by changes in precipitation and find that landslide velocity varies over both timescales. Over seasonal timescales, each landslide displays a period of acceleration that occurs within weeks of the onset of seasonal rainfall suggesting that motion is governed by precipitation-induced changes in pore-water pressure. We also examine the effects of multi-year climate variations (i.e., recent historic California drought and the possible wet period that began in late 2016) on the activity of landslides. We find that the drought has led to a decrease in annual displacement over the past several years and predict that a resurgence in annual displacement will occur with an increase in annual rainfall. Lastly, we use UAVSAR data acquired at 4 different look directions to quantify 3D surface displacement of multiple landslides and invert for their subsurface geometry (i.e. basal slip surface) using recently developed 3D mass conservation techniques. The application of NASA's UAVSAR data represents a major advance from previous InSAR studies on landslides in this region and provides one of the first 3D dataset that contains

  19. Whole-genome sequencing of Bacillus subtilis XF-1 reveals mechanisms for biological control and multiple beneficial properties in plants.

    Science.gov (United States)

    Guo, Shengye; Li, Xingyu; He, Pengfei; Ho, Honhing; Wu, Yixin; He, Yueqiu

    2015-06-01

    Bacillus subtilis XF-1 is a gram-positive, plant-associated bacterium that stimulates plant growth and produces secondary metabolites that suppress soil-borne plant pathogens. In particular, it is especially highly efficient at controlling the clubroot disease of cruciferous crops. Its 4,061,186-bp genome contains an estimated 3853 protein-coding sequences and the 1155 genes of XF-1 are present in most genome-sequenced Bacillus strains: 3757 genes in B. subtilis 168, and 1164 in B. amyloliquefaciens FZB42. Analysis using the Cluster of Orthologous Groups database of proteins shows that 60 genes control bacterial mobility, 221 genes are related to cell wall and membrane biosynthesis, and more than 112 are genes associated with secondary metabolites. In addition, the genes contributed to the strain's plant colonization, bio-control and stimulation of plant growth. Sequencing of the genome is a fundamental step for developing a desired strain to serve as an efficient biological control agent and plant growth stimulator. Similar to other members of the taxon, XF-1 has a genome that contains giant gene clusters for the non-ribosomal synthesis of antifungal lipopeptides (surfactin and fengycin), the polyketides (macrolactin and bacillaene), the siderophore bacillibactin, and the dipeptide bacilysin. There are two synthesis pathways for volatile growth-promoting compounds. The expression of biosynthesized antibiotic peptides in XF-1 was revealed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry.

  20. Revealing the control of migratory fueling: An integrated approach combining laboratory and field studies in northern wheatears Oenanthe oenanthe

    Directory of Open Access Journals (Sweden)

    Franz BAIRLEIN,Volker DIERSCHKE, Julia DELINGAT, Cas EIKENAAR, Ivan MAGGINI, Marc BULTE, Heiko SCHMALJOHANN

    2013-06-01

    Full Text Available Migratory birds rely on fueling prior to migratory flights. Fueling in migrants is controlled by intrinsic as well as extrinsic factors. From captive studies we have started understanding the internal mechanisms controlling bird migration. Field studies have demonstrated the effects of external factors, such as food availability, weather, competitors, parasites or diseases, on the stopover behavior of migrants. However, an integrated approach is still missing to study coherently how the innate migration program interacts with the varying environmental cues and to estimate the contribution of the innate migration program and the environment to realized migration. The northern wheatear Oenanthe oenanthe offers a unique opportunity for integrated studies. It breeds across almost the whole Holarctic with just a “gap” between eastern Canada and Alaska. All breeding populations overwinter in sub-Saharan Africa which makes the northern wheatear one of the most long-distant migratory songbirds with extraordinary long non-stop flights across oceans. It is a nocturnal migrant which travels without parental or social aid/guidance. Thus, young birds rely entirely on endogenous mechanisms of timing, route selection and fueling on their first outbound migration. By establishing indoor housing under controlled conditions the endogenous control mechanisms of northern wheatear migration could be revealed. At the same time, environmental factors controlling fueling could be investigated in the field. On migration wheatears occur in a variety of habitats with sparse vegetation where their stopover behavior could be quantitatively studied in the light of “optimal migration” theory by the use of remote balances, radio-tagging and even experimentally manipulated food availability. The present paper summarizes our approach to understand the control of migration in northern wheatears by combining field and laboratory studies at various spatial and temporal

  1. Phase-specific Surround suppression in Mouse Primary Visual Cortex Correlates with Figure Detection Behavior Based on Phase Discontinuity.

    Science.gov (United States)

    Li, Fengling; Jiang, Weiqian; Wang, Tian-Yi; Xie, Taorong; Yao, Haishan

    2018-05-21

    In the primary visual cortex (V1), neuronal responses to stimuli within the receptive field (RF) are modulated by stimuli in the RF surround. A common effect of surround modulation is surround suppression, which is dependent on the feature difference between stimuli within and surround the RF and is suggested to be involved in the perceptual phenomenon of figure-ground segregation. In this study, we examined the relationship between feature-specific surround suppression of V1 neurons and figure detection behavior based on figure-ground feature difference. We trained freely moving mice to perform a figure detection task using figure and ground gratings that differed in spatial phase. The performance of figure detection increased with the figure-ground phase difference, and was modulated by stimulus contrast. Electrophysiological recordings from V1 in head-fixed mice showed that the increase in phase difference between stimuli within and surround the RF caused a reduction in surround suppression, which was associated with an increase in V1 neural discrimination between stimuli with and without RF-surround phase difference. Consistent with the behavioral performance, the sensitivity of V1 neurons to RF-surround phase difference could be influenced by stimulus contrast. Furthermore, inhibiting V1 by optogenetically activating either parvalbumin (PV)- or somatostatin (SOM)-expressing inhibitory neurons both decreased the behavioral performance of figure detection. Thus, the phase-specific surround suppression in V1 represents a neural correlate of figure detection behavior based on figure-ground phase discontinuity. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. No Evidence for Phase-Specific Effects of 40 Hz HD–tACS on Multiple Object Tracking

    Directory of Open Access Journals (Sweden)

    Nicholas S. Bland

    2018-03-01

    Full Text Available Phase synchronization drives connectivity between neural oscillators, providing a flexible mechanism through which information can be effectively and selectively routed between task-relevant cortical areas. The ability to keep track of objects moving between the left and right visual hemifields, for example, requires the integration of information between the two cerebral hemispheres. Both animal and human studies have suggested that coherent (or phase-locked gamma oscillations (30–80 Hz might underlie this ability. While most human evidence has been strictly correlational, high-density transcranial alternating current stimulation (HD-tACS has been used to manipulate ongoing interhemispheric gamma phase relationships. Previous research showed that 40 Hz tACS delivered bilaterally over human motion complex could bias the perception of a bistable ambiguous motion stimulus (Helfrich et al., 2014. Specifically, this work showed that in-phase (0° offset stimulation boosted endogenous interhemispheric gamma coherence and biased perception toward the horizontal (whereby visual tokens moved between visual hemifields—requiring interhemispheric integration. By contrast, anti-phase (180° offset stimulation decreased interhemispheric gamma coherence and biased perception toward the vertical (whereby tokens moved within separate visual hemifields. Here we devised a multiple object tracking arena comprised of four quadrants whereby discrete objects moved either entirely within the left and right visual hemifields, or could cross freely between visual hemifields, thus requiring interhemispheric integration. Using the same HD-tACS montages as Helfrich et al. (2014, we found no phase-specific effect of 40 Hz stimulation on overall tracking performance. While tracking performance was generally lower during between-hemifield trials (presumably reflecting a cost of integration, this difference was unchanged by in- vs. anti-phase stimulation. Our null results

  3. Visual guidance of forward flight in hummingbirds reveals control based on image features instead of pattern velocity.

    Science.gov (United States)

    Dakin, Roslyn; Fellows, Tyee K; Altshuler, Douglas L

    2016-08-02

    Information about self-motion and obstacles in the environment is encoded by optic flow, the movement of images on the eye. Decades of research have revealed that flying insects control speed, altitude, and trajectory by a simple strategy of maintaining or balancing the translational velocity of images on the eyes, known as pattern velocity. It has been proposed that birds may use a similar algorithm but this hypothesis has not been tested directly. We examined the influence of pattern velocity on avian flight by manipulating the motion of patterns on the walls of a tunnel traversed by Anna's hummingbirds. Contrary to prediction, we found that lateral course control is not based on regulating nasal-to-temporal pattern velocity. Instead, birds closely monitored feature height in the vertical axis, and steered away from taller features even in the absence of nasal-to-temporal pattern velocity cues. For vertical course control, we observed that birds adjusted their flight altitude in response to upward motion of the horizontal plane, which simulates vertical descent. Collectively, our results suggest that birds avoid collisions using visual cues in the vertical axis. Specifically, we propose that birds monitor the vertical extent of features in the lateral visual field to assess distances to the side, and vertical pattern velocity to avoid collisions with the ground. These distinct strategies may derive from greater need to avoid collisions in birds, compared with small insects.

  4. Biosynthesis of Antibiotic Leucinostatins in Bio-control Fungus Purpureocillium lilacinum and Their Inhibition on Phytophthora Revealed by Genome Mining.

    Directory of Open Access Journals (Sweden)

    Gang Wang

    2016-07-01

    Full Text Available Purpureocillium lilacinum of Ophiocordycipitaceae is one of the most promising and commercialized agents for controlling plant parasitic nematodes, as well as other insects and plant pathogens. However, how the fungus functions at the molecular level remains unknown. Here, we sequenced two isolates (PLBJ-1 and PLFJ-1 of P. lilacinum from different places Beijing and Fujian. Genomic analysis showed high synteny of the two isolates, and the phylogenetic analysis indicated they were most related to the insect pathogen Tolypocladium inflatum. A comparison with other species revealed that this fungus was enriched in carbohydrate-active enzymes (CAZymes, proteases and pathogenesis related genes. Whole genome search revealed a rich repertoire of secondary metabolites (SMs encoding genes. The non-ribosomal peptide synthetase LcsA, which is comprised of ten C-A-PCP modules, was identified as the core biosynthetic gene of lipopeptide leucinostatins, which was specific to P. lilacinum and T. ophioglossoides, as confirmed by phylogenetic analysis. Furthermore, gene expression level was analyzed when PLBJ-1 was grown in leucinostatin-inducing and non-inducing medium, and 20 genes involved in the biosynthesis of leucionostatins were identified. Disruption mutants allowed us to propose a putative biosynthetic pathway of leucinostatin A. Moreover, overexpression of the transcription factor lcsF increased the production (1.5-fold of leucinostatins A and B compared to wild type. Bioassays explored a new bioactivity of leucinostatins and P. lilacinum: inhibiting the growth of Phytophthora infestans and P. capsici. These results contribute to our understanding of the biosynthetic mechanism of leucinostatins and may allow us to utilize P. lilacinum better as bio-control agent.

  5. Representing Microbial Dormancy in Soil Decomposition Models Improves Model Performance and Reveals Key Ecosystem Controls on Microbial Activity

    Science.gov (United States)

    He, Y.; Yang, J.; Zhuang, Q.; Wang, G.; Liu, Y.

    2014-12-01

    Climate feedbacks from soils can result from environmental change and subsequent responses of plant and microbial communities and nutrient cycling. Explicit consideration of microbial life history traits and strategy may be necessary to predict climate feedbacks due to microbial physiology and community changes and their associated effect on carbon cycling. In this study, we developed an explicit microbial-enzyme decomposition model and examined model performance with and without representation of dormancy at six temperate forest sites with observed soil efflux ranged from 4 to 10 years across different forest types. We then extrapolated the model to all temperate forests in the Northern Hemisphere (25-50°N) to investigate spatial controls on microbial and soil C dynamics. Both models captured the observed soil heterotrophic respiration (RH), yet no-dormancy model consistently exhibited large seasonal amplitude and overestimation in microbial biomass. Spatially, the total RH from temperate forests based on dormancy model amounts to 6.88PgC/yr, and 7.99PgC/yr based on no-dormancy model. However, no-dormancy model notably overestimated the ratio of microbial biomass to SOC. Spatial correlation analysis revealed key controls of soil C:N ratio on the active proportion of microbial biomass, whereas local dormancy is primarily controlled by soil moisture and temperature, indicating scale-dependent environmental and biotic controls on microbial and SOC dynamics. These developments should provide essential support to modeling future soil carbon dynamics and enhance the avenue for collaboration between empirical soil experiment and modeling in the sense that more microbial physiological measurements are needed to better constrain and evaluate the models.

  6. A Knockout Screen of ApiAP2 Genes Reveals Networks of Interacting Transcriptional Regulators Controlling the Plasmodium Life Cycle.

    Science.gov (United States)

    Modrzynska, Katarzyna; Pfander, Claudia; Chappell, Lia; Yu, Lu; Suarez, Catherine; Dundas, Kirsten; Gomes, Ana Rita; Goulding, David; Rayner, Julian C; Choudhary, Jyoti; Billker, Oliver

    2017-01-11

    A family of apicomplexa-specific proteins containing AP2 DNA-binding domains (ApiAP2s) was identified in malaria parasites. This family includes sequence-specific transcription factors that are key regulators of development. However, functions for the majority of ApiAP2 genes remain unknown. Here, a systematic knockout screen in Plasmodium berghei identified ten ApiAP2 genes that were essential for mosquito transmission: four were critical for the formation of infectious ookinetes, and three were required for sporogony. We describe non-essential functions for AP2-O and AP2-SP proteins in blood stages, and identify AP2-G2 as a repressor active in both asexual and sexual stages. Comparative transcriptomics across mutants and developmental stages revealed clusters of co-regulated genes with shared cis promoter elements, whose expression can be controlled positively or negatively by different ApiAP2 factors. We propose that stage-specific interactions between ApiAP2 proteins on partly overlapping sets of target genes generate the complex transcriptional network that controls the Plasmodium life cycle. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. A functional screen reveals an extensive layer of transcriptional and splicing control underlying RAS/MAPK signaling in Drosophila.

    Directory of Open Access Journals (Sweden)

    Dariel Ashton-Beaucage

    2014-03-01

    Full Text Available The small GTPase RAS is among the most prevalent oncogenes. The evolutionarily conserved RAF-MEK-MAPK module that lies downstream of RAS is one of the main conduits through which RAS transmits proliferative signals in normal and cancer cells. Genetic and biochemical studies conducted over the last two decades uncovered a small set of factors regulating RAS/MAPK signaling. Interestingly, most of these were found to control RAF activation, thus suggesting a central regulatory role for this event. Whether additional factors are required at this level or further downstream remains an open question. To obtain a comprehensive view of the elements functionally linked to the RAS/MAPK cascade, we used a quantitative assay in Drosophila S2 cells to conduct a genome-wide RNAi screen for factors impacting RAS-mediated MAPK activation. The screen led to the identification of 101 validated hits, including most of the previously known factors associated to this pathway. Epistasis experiments were then carried out on individual candidates to determine their position relative to core pathway components. While this revealed several new factors acting at different steps along the pathway--including a new protein complex modulating RAF activation--we found that most hits unexpectedly work downstream of MEK and specifically influence MAPK expression. These hits mainly consist of constitutive splicing factors and thereby suggest that splicing plays a specific role in establishing MAPK levels. We further characterized two representative members of this group and surprisingly found that they act by regulating mapk alternative splicing. This study provides an unprecedented assessment of the factors modulating RAS/MAPK signaling in Drosophila. In addition, it suggests that pathway output does not solely rely on classical signaling events, such as those controlling RAF activation, but also on the regulation of MAPK levels. Finally, it indicates that core splicing

  8. Meta-analysis reveals host-dependent nitrogen recycling as a mechanism of symbiont control in Aiptasia

    KAUST Repository

    Cui, Guoxin

    2018-02-22

    The metabolic symbiosis with photosynthetic algae of the genus Symbiodinium allows corals to thrive in the oligotrophic environments of tropical seas. Many aspects of this relationship have been investigated using transcriptomic analyses in the emerging model organism Aiptasia. However, previous studies identified thousands of putatively symbiosis-related genes, making it difficult to disentangle symbiosis-induced responses from undesired experimental parameters. Using a meta-analysis approach, we identified a core set of 731 high-confidence symbiosis-associated genes that reveal host-dependent recycling of waste ammonium and amino acid synthesis as central processes in this relationship. Combining transcriptomic and metabolomic analyses, we show that symbiont-derived carbon enables host recycling of ammonium into nonessential amino acids. We propose that this provides a regulatory mechanism to control symbiont growth through a carbon-dependent negative feedback of nitrogen availability to the symbiont. The dependence of this mechanism on symbiont-derived carbon highlights the susceptibility of this symbiosis to changes in carbon translocation, as imposed by environmental stress.

  9. A comprehensive custom panel design for routine hereditary cancer testing: preserving control, improving diagnostics and revealing a complex variation landscape.

    Science.gov (United States)

    Castellanos, Elisabeth; Gel, Bernat; Rosas, Inma; Tornero, Eva; Santín, Sheila; Pluvinet, Raquel; Velasco, Juan; Sumoy, Lauro; Del Valle, Jesús; Perucho, Manuel; Blanco, Ignacio; Navarro, Matilde; Brunet, Joan; Pineda, Marta; Feliubadaló, Lidia; Capellá, Gabi; Lázaro, Conxi; Serra, Eduard

    2017-01-04

    We wanted to implement an NGS strategy to globally analyze hereditary cancer with diagnostic quality while retaining the same degree of understanding and control we had in pre-NGS strategies. To do this, we developed the I2HCP panel, a custom bait library covering 122 hereditary cancer genes. We improved bait design, tested different NGS platforms and created a clinically driven custom data analysis pipeline. The I2HCP panel was developed using a training set of hereditary colorectal cancer, hereditary breast and ovarian cancer and neurofibromatosis patients and reached an accuracy, analytical sensitivity and specificity greater than 99%, which was maintained in a validation set. I2HCP changed our diagnostic approach, involving clinicians and a genetic diagnostics team from panel design to reporting. The new strategy improved diagnostic sensitivity, solved uncertain clinical diagnoses and identified mutations in new genes. We assessed the genetic variation in the complete set of hereditary cancer genes, revealing a complex variation landscape that coexists with the disease-causing mutation. We developed, validated and implemented a custom NGS-based strategy for hereditary cancer diagnostics that improved our previous workflows. Additionally, the existence of a rich genetic variation in hereditary cancer genes favors the use of this panel to investigate their role in cancer risk.

  10. Metabolomics reveals the metabolic shifts following an intervention with rye bread in postmenopausal women- a randomized control trial

    Directory of Open Access Journals (Sweden)

    Moazzami Ali A

    2012-10-01

    Full Text Available Abstract Background Epidemiological studies have consistently shown that whole grain (WG cereals can protect against the development of chronic diseases, but the underlying mechanism is not fully understood. Among WG products, WG rye is considered even more potent because of its unique discrepancy in postprandial insulin and glucose responses known as the rye factor. In this study, an NMR-based metabolomics approach was applied to study the metabolic effects of WG rye as a tool to determine the beneficial effects of WG rye on human health. Methods Thirty-three postmenopausal Finnish women with elevated serum total cholesterol (5.0-8.5 mmol/L and BMI of 20–33 kg/m2 consumed a minimum of 20% of their daily energy intake as high fiber WG rye bread (RB or refined wheat bread (WB in a randomized, controlled, crossover design with two 8-wk intervention periods separated by an 8-wk washout period. At the end of each intervention period, fasting serum was collected for NMR-based metabolomics and the analysis of cholesterol fractions. Multilevel partial least squares discriminant analysis was used for paired comparisons of multivariate data. Results The metabolomics analysis of serum showed lower leucine and isoleucine and higher betaine and N,N-dimethylglycine levels after RB than WB intake. To further investigate the metabolic effects of RB, the serum cholesterol fractions were measured. Total- and LDL-cholesterol levels were higher after RB intake than after WB (p Conclusions This study revealed favorable shifts in branched amino acid and single carbon metabolism and an unfavorable shift in serum cholesterol levels after RB intake in postmenopausal women, which should be considered for evaluating health beneficial effects of rye products.

  11. Transcriptome analysis reveals self-incompatibility in the tea plant (Camellia sinensis) might be under gametophytic control.

    Science.gov (United States)

    Zhang, Cheng-Cai; Wang, Li-Yuan; Wei, Kang; Wu, Li-Yun; Li, Hai-Lin; Zhang, Fen; Cheng, Hao; Ni, De-Jiang

    2016-05-17

    Self-incompatibility (SI) is under genetic control and prevents inbreeding depression in angiosperms. SI mechanisms are quite complicated and still poorly understood in many plants. Tea (Camellia sinensis L.) belonging to the family of Theaceae, exhibits high levels of SI and high heterozygosity. Uncovering the molecular basis of SI of the tea plant may enhance breeding and simplify genomics research for the whole family. The growth of pollen tubes following selfing and crossing was observed using fluorescence microscopy. Self-pollen tubes grew slower than cross treatments from 24 h to 72 h after pollination. RNA-seq was employed to explore the molecular mechanisms of SI and to identify SI-related genes in C. sinensis. Self and cross-pollinated styles were collected at 24 h, 48 h and 72 h after pollination. Six RNA-seq libraries (SP24, SP48, SP72, CP24 CP48 and CP72; SP = self-pollinated, CP = cross-pollinated) were constructed and separately sequenced. In total, 299.327 million raw reads were generated. Following assembly, 63,762 unigenes were identified, and 27,264 (42.76 %) unigenes were annotated in five public databases: NR, KOG, KEGG, Swiss-Port and GO. To identify SI-related genes, the fragments per kb per million mapped reads (FPKM) values of each unigene were evaluated. Comparisons of CP24 vs. SP24, CP48 vs. SP48 and CP72 vs. SP72 revealed differential expression of 3,182, 3,575 and 3,709 genes, respectively. Consequently, several ubiquitin-mediated proteolysis, Ca(2+) signaling, apoptosis and defense-associated genes were obtained. The temporal expression pattern of genes following CP and SP was analyzed; 6 peroxidase, 1 polyphenol oxidase and 7 salicylic acid biosynthetic process-related genes were identified. The RNA-seq data were validated by qRT-PCR of 15 unigenes. Finally, a unigene (CL25983Contig1) with strong homology to the S-RNase was analyzed. It was mainly expressed in styles, with dramatically higher expression in self

  12. Single-Amino Acid Modifications Reveal Additional Controls on the Proton Pathway of [FeFe]-Hydrogenase

    Energy Technology Data Exchange (ETDEWEB)

    Cornish, Adam J.; Ginovska, Bojana; Thelen, Adam; da Silva, Julio C. S.; Soares, Thereza A.; Raugei, Simone; Dupuis, Michel; Shaw, Wendy J.; Hegg, Eric L.

    2016-06-07

    The proton pathway of [FeFe]-hydrogenase is essential for enzymatic H2 production and oxidation and is composed of four residues and a modeled water molecule. Recently, a computational analysis of this pathway revealed that the solvent-exposed residue of the pathway (Glu282) could form hydrogen bonds to two residues outside of the pathway (Arg286 and Ser320), implicating that these residues could function in regulating proton transfer. Substituting Arg286 with leucine eliminates hydrogen bonding with Glu282 and results in a 2.5-fold enhancement in H2 production activity, suggesting that Arg286 serves an important role in controlling the rate of proton delivery. In contrast, substitution of Ser320 with alanine reduces the rate approximately 5-fold, implying that it either acts as a member of the pathway or influences Glu282 to enable proton transfer. Interestingly, QM/MM and molecular dynamics calculations indicate that Ser320 does not play an electronic or structural role. QM calculations also estimate that including Ser320 in the pathway does not significantly change the barrier to proton movement, providing further support for its role as a member of the proton pathway. While further studies are needed to quantify the role of Ser320, collectively, these data provide evidence that the enzyme scaffold plays a significant role in modulating the activity of the enzyme, demonstrating that the rate of intraprotein proton transfer can be accelerated, particularly in a non-biological context. This work was supported by the DOE Great Lakes Bioenergy Research Center (DOE BER Office of Science, DE-FC02-07ER64494). In addition, support from the DOE Office of Science Early Career Research Program through the Office of Basic Energy Sciences (WJS, BGP, SR) is gratefully acknowledged. Computational resources were provided at W. R. Wiley Environmental Molecular Science Laboratory (EMSL), a national scientific user facility sponsored by the Department of Energy’s Office of

  13. Curcumin's Neuroprotective Efficacy in Drosophila Model of Idiopathic Parkinson's Disease Is Phase Specific: Implication of its Therapeutic Effectiveness

    Science.gov (United States)

    Phom, Limamanen; Achumi, Bovito; Alone, Debasmita P.; Muralidhara

    2014-01-01

    Abstract Selective degeneration of dopaminergic neurons in the substantia nigra underlies the basic motor impairments of Parkinson's disease (PD). Curcumin has been used for centuries in traditional medicines in India. Our aim is to understand the efficacy of genotropic drug curcumin as a neuroprotective agent in PD. Analysis of different developmental stages in model organisms revealed that they are characterized by different patterns of gene expression which is similar to that of developmental stages of human. Genotropic drugs would be effective only during those life cycle stages for which their target molecules are available. Hence there exists a possibility that targets of genotropic compounds such as curcumin may not be present in all life stages. However, no reports are available in PD models illustrating the efficacy of curcumin in later phases of adult life. This is important because this is the period during which late-onset disorders such as idiopathic PD set in. To understand this paradigm, we tested the protective efficacy of curcumin in different growth stages (early, late health stage, and transition phase) in adult Drosophila flies. Results showed that it can rescue the motor defects during early stages of life but is ineffective at later phases. This observation was substantiated with the finding that curcumin treatment could replenish depleted brain dopamine levels in the PD model only during early stages of life cycle, clearly suggesting its limitation as a therapeutic agent in late-onset neurodegenerative disorders such as PD. PMID:25238331

  14. A closer look at cognitive control: Differences in resource allocation during updating, inhibition and switching as revealed by pupillometry

    NARCIS (Netherlands)

    Rondeel, E.W.M.; Steenbergen, H. van; Holland, R.W.; Knippenberg, A.F.M. van

    2015-01-01

    The present study investigated resource allocation, as measured by pupil dilation, in tasks measuring updating (2 Back task), inhibition (Stroop task) and switching (Number Switch task). Because each cognitive control component has unique characteristics, differences in patterns of resource

  15. A high-density ERP study reveals latency, amplitude, and topographical differences in multiple sclerosis patients versus controls.

    LENUS (Irish Health Repository)

    Whelan, R

    2012-02-01

    OBJECTIVE: To quantify latency, amplitude and topographical differences in event-related potential (ERP) components between multiple sclerosis (MS) patients and controls and to compare ERP findings with results from the paced auditory serial addition test (PASAT). METHODS: Fifty-four subjects (17 relapsing remitting (RRMS) patients, 16 secondary progressive (SPMS) patients, and 21 controls) completed visual and auditory oddball tasks while data were recorded from 134 EEG channels. Latency and amplitude differences, calculated using composite mean amplitude measures, were tested using an ANOVA. Topographical differences were tested using statistical parametric mapping (SPM). RESULTS: In the visual modality, P2, P3 amplitudes and N2 latency were significantly different across groups. In the auditory modality, P2, N2, and P3 latencies and N1 amplitude were significantly different across groups. There were no significant differences between RRMS and SPMS patients on any ERP component. There were topographical differences between MS patients and controls for both early and late components for the visual modality, but only in the early components for the auditory modality. PASAT score correlated significantly with auditory P3 latency for MS patients. CONCLUSIONS: There were significant ERP differences between MS patients and controls. SIGNIFICANCE: The present study indicated that both early sensory and later cognitive ERP components are impaired in MS patients relative to controls.

  16. Magnetic resonance imaging reveals altered distribution of hepatic fat in children with type 1 diabetes compared to controls.

    Science.gov (United States)

    Regnell, Simon E; Peterson, Pernilla; Trinh, Lena; Broberg, Per; Leander, Peter; Lernmark, Åke; Månsson, Sven; Elding Larsson, Helena

    2015-08-01

    Children with type 1 diabetes have been identified as a risk group for non-alcoholic fatty liver disease (NAFLD). The aim was to compare total hepatic fat fraction and fat distribution across Couinaud segments in children with type 1 diabetes and controls and the relation of hepatic fat to plasma and anthropometric parameters. Hepatic fat fraction and fat distribution across Couinaud segments were measured with magnetic resonance imaging (MRI) in 22 children with type 1 diabetes and 32 controls. Blood tests and anthropometric data were collected. No children had NAFLD. Children with type 1 diabetes had a slightly lower hepatic fat fraction (median 1.3%) than controls (median 1.8%), and their fat had a different segmental distribution. The fat fraction of segment V was the most representative of the liver as a whole. An incidental finding was that diabetes patients treated with multiple daily injections of insulin (MDI) had a fat distribution more similar to controls than patients with continuous subcutaneous insulin infusion (CSII). In children with type 1 diabetes, NAFLD may be less common than recent studies have suggested. Children with type 1 diabetes may have a lower fat fraction and a different fat distribution in the liver than controls. Diabetes treatment with MDI or CSII may affect liver fat, but this needs to be confirmed in a larger sample of patients. The heterogeneity of hepatic fat infiltration may affect results when liver biopsy is used for diagnosing fatty liver. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Single-Cell Analyses of ESCs Reveal Alternative Pluripotent Cell States and Molecular Mechanisms that Control Self-Renewal

    Directory of Open Access Journals (Sweden)

    Dmitri Papatsenko

    2015-08-01

    Full Text Available Analyses of gene expression in single mouse embryonic stem cells (mESCs cultured in serum and LIF revealed the presence of two distinct cell subpopulations with individual gene expression signatures. Comparisons with published data revealed that cells in the first subpopulation are phenotypically similar to cells isolated from the inner cell mass (ICM. In contrast, cells in the second subpopulation appear to be more mature. Pluripotency Gene Regulatory Network (PGRN reconstruction based on single-cell data and published data suggested antagonistic roles for Oct4 and Nanog in the maintenance of pluripotency states. Integrated analyses of published genomic binding (ChIP data strongly supported this observation. Certain target genes alternatively regulated by OCT4 and NANOG, such as Sall4 and Zscan10, feed back into the top hierarchical regulator Oct4. Analyses of such incoherent feedforward loops with feedback (iFFL-FB suggest a dynamic model for the maintenance of mESC pluripotency and self-renewal.

  18. Gender-Differentiated Parenting Revisited: Meta-Analysis Reveals Very Few Differences in Parental Control of Boys and Girls

    Science.gov (United States)

    Endendijk, Joyce J.; Groeneveld, Marleen G.; Bakermans-Kranenburg, Marian J.; Mesman, Judi

    2016-01-01

    Although various theories describe mechanisms leading to differential parenting of boys and girls, there is no consensus about the extent to which parents do treat their sons and daughters differently. The last meta-analyses on the subject were conducted more than fifteen years ago, and changes in gender-specific child rearing in the past decade are quite plausible. In the current set of meta-analyses, based on 126 observational studies (15,034 families), we examined mothers’ and fathers’ differential use of autonomy-supportive and controlling strategies with boys and girls, and the role of moderators related to the decade in which the study was conducted, the observational context, and sample characteristics. Databases of Web of Science, ERIC, PsychInfo, Online Contents, Picarta, and Proquest were searched for studies examining differences in observed parental control of boys and girls between the ages of 0 and 18 years. Few differences were found in parents’ use of control with boys and girls. Parents were slightly more controlling with boys than with girls, but the effect size was negligible (d = 0.08). The effect was larger, but still small, in normative groups and in samples with younger children. No overall effect for gender-differentiated autonomy-supportive strategies was found (d = 0.03). A significant effect of time emerged: studies published in the 1970s and 1980s reported more autonomy-supportive strategies with boys than toward girls, but from 1990 onwards parents showed somewhat more autonomy-supportive strategies with girls than toward boys. Taking into account parents’ gender stereotypes might uncover subgroups of families where gender-differentiated control is salient, but based on our systematic review of the currently available large data base we conclude that in general the differences between parenting of boys versus girls are minimal. PMID:27416099

  19. Gender-Differentiated Parenting Revisited: Meta-Analysis Reveals Very Few Differences in Parental Control of Boys and Girls.

    Directory of Open Access Journals (Sweden)

    Joyce J Endendijk

    Full Text Available Although various theories describe mechanisms leading to differential parenting of boys and girls, there is no consensus about the extent to which parents do treat their sons and daughters differently. The last meta-analyses on the subject were conducted more than fifteen years ago, and changes in gender-specific child rearing in the past decade are quite plausible. In the current set of meta-analyses, based on 126 observational studies (15,034 families, we examined mothers' and fathers' differential use of autonomy-supportive and controlling strategies with boys and girls, and the role of moderators related to the decade in which the study was conducted, the observational context, and sample characteristics. Databases of Web of Science, ERIC, PsychInfo, Online Contents, Picarta, and Proquest were searched for studies examining differences in observed parental control of boys and girls between the ages of 0 and 18 years. Few differences were found in parents' use of control with boys and girls. Parents were slightly more controlling with boys than with girls, but the effect size was negligible (d = 0.08. The effect was larger, but still small, in normative groups and in samples with younger children. No overall effect for gender-differentiated autonomy-supportive strategies was found (d = 0.03. A significant effect of time emerged: studies published in the 1970s and 1980s reported more autonomy-supportive strategies with boys than toward girls, but from 1990 onwards parents showed somewhat more autonomy-supportive strategies with girls than toward boys. Taking into account parents' gender stereotypes might uncover subgroups of families where gender-differentiated control is salient, but based on our systematic review of the currently available large data base we conclude that in general the differences between parenting of boys versus girls are minimal.

  20. Gender-Differentiated Parenting Revisited: Meta-Analysis Reveals Very Few Differences in Parental Control of Boys and Girls.

    Science.gov (United States)

    Endendijk, Joyce J; Groeneveld, Marleen G; Bakermans-Kranenburg, Marian J; Mesman, Judi

    2016-01-01

    Although various theories describe mechanisms leading to differential parenting of boys and girls, there is no consensus about the extent to which parents do treat their sons and daughters differently. The last meta-analyses on the subject were conducted more than fifteen years ago, and changes in gender-specific child rearing in the past decade are quite plausible. In the current set of meta-analyses, based on 126 observational studies (15,034 families), we examined mothers' and fathers' differential use of autonomy-supportive and controlling strategies with boys and girls, and the role of moderators related to the decade in which the study was conducted, the observational context, and sample characteristics. Databases of Web of Science, ERIC, PsychInfo, Online Contents, Picarta, and Proquest were searched for studies examining differences in observed parental control of boys and girls between the ages of 0 and 18 years. Few differences were found in parents' use of control with boys and girls. Parents were slightly more controlling with boys than with girls, but the effect size was negligible (d = 0.08). The effect was larger, but still small, in normative groups and in samples with younger children. No overall effect for gender-differentiated autonomy-supportive strategies was found (d = 0.03). A significant effect of time emerged: studies published in the 1970s and 1980s reported more autonomy-supportive strategies with boys than toward girls, but from 1990 onwards parents showed somewhat more autonomy-supportive strategies with girls than toward boys. Taking into account parents' gender stereotypes might uncover subgroups of families where gender-differentiated control is salient, but based on our systematic review of the currently available large data base we conclude that in general the differences between parenting of boys versus girls are minimal.

  1. Dual dimensionality reduction reveals independent encoding of motor features in a muscle synergy for insect flight control.

    Science.gov (United States)

    Sponberg, Simon; Daniel, Thomas L; Fairhall, Adrienne L

    2015-04-01

    What are the features of movement encoded by changing motor commands? Do motor commands encode movement independently or can they be represented in a reduced set of signals (i.e. synergies)? Motor encoding poses a computational and practical challenge because many muscles typically drive movement, and simultaneous electrophysiology recordings of all motor commands are typically not available. Moreover, during a single locomotor period (a stride or wingstroke) the variation in movement may have high dimensionality, even if only a few discrete signals activate the muscles. Here, we apply the method of partial least squares (PLS) to extract the encoded features of movement based on the cross-covariance of motor signals and movement. PLS simultaneously decomposes both datasets and identifies only the variation in movement that relates to the specific muscles of interest. We use this approach to explore how the main downstroke flight muscles of an insect, the hawkmoth Manduca sexta, encode torque during yaw turns. We simultaneously record muscle activity and turning torque in tethered flying moths experiencing wide-field visual stimuli. We ask whether this pair of muscles acts as a muscle synergy (a single linear combination of activity) consistent with their hypothesized function of producing a left-right power differential. Alternatively, each muscle might individually encode variation in movement. We show that PLS feature analysis produces an efficient reduction of dimensionality in torque variation within a wingstroke. At first, the two muscles appear to behave as a synergy when we consider only their wingstroke-averaged torque. However, when we consider the PLS features, the muscles reveal independent encoding of torque. Using these features we can predictably reconstruct the variation in torque corresponding to changes in muscle activation. PLS-based feature analysis provides a general two-sided dimensionality reduction that reveals encoding in high dimensional

  2. Dual dimensionality reduction reveals independent encoding of motor features in a muscle synergy for insect flight control.

    Directory of Open Access Journals (Sweden)

    Simon Sponberg

    2015-04-01

    Full Text Available What are the features of movement encoded by changing motor commands? Do motor commands encode movement independently or can they be represented in a reduced set of signals (i.e. synergies? Motor encoding poses a computational and practical challenge because many muscles typically drive movement, and simultaneous electrophysiology recordings of all motor commands are typically not available. Moreover, during a single locomotor period (a stride or wingstroke the variation in movement may have high dimensionality, even if only a few discrete signals activate the muscles. Here, we apply the method of partial least squares (PLS to extract the encoded features of movement based on the cross-covariance of motor signals and movement. PLS simultaneously decomposes both datasets and identifies only the variation in movement that relates to the specific muscles of interest. We use this approach to explore how the main downstroke flight muscles of an insect, the hawkmoth Manduca sexta, encode torque during yaw turns. We simultaneously record muscle activity and turning torque in tethered flying moths experiencing wide-field visual stimuli. We ask whether this pair of muscles acts as a muscle synergy (a single linear combination of activity consistent with their hypothesized function of producing a left-right power differential. Alternatively, each muscle might individually encode variation in movement. We show that PLS feature analysis produces an efficient reduction of dimensionality in torque variation within a wingstroke. At first, the two muscles appear to behave as a synergy when we consider only their wingstroke-averaged torque. However, when we consider the PLS features, the muscles reveal independent encoding of torque. Using these features we can predictably reconstruct the variation in torque corresponding to changes in muscle activation. PLS-based feature analysis provides a general two-sided dimensionality reduction that reveals encoding in

  3. Dual Dimensionality Reduction Reveals Independent Encoding of Motor Features in a Muscle Synergy for Insect Flight Control

    Science.gov (United States)

    Sponberg, Simon; Daniel, Thomas L.; Fairhall, Adrienne L.

    2015-01-01

    What are the features of movement encoded by changing motor commands? Do motor commands encode movement independently or can they be represented in a reduced set of signals (i.e. synergies)? Motor encoding poses a computational and practical challenge because many muscles typically drive movement, and simultaneous electrophysiology recordings of all motor commands are typically not available. Moreover, during a single locomotor period (a stride or wingstroke) the variation in movement may have high dimensionality, even if only a few discrete signals activate the muscles. Here, we apply the method of partial least squares (PLS) to extract the encoded features of movement based on the cross-covariance of motor signals and movement. PLS simultaneously decomposes both datasets and identifies only the variation in movement that relates to the specific muscles of interest. We use this approach to explore how the main downstroke flight muscles of an insect, the hawkmoth Manduca sexta, encode torque during yaw turns. We simultaneously record muscle activity and turning torque in tethered flying moths experiencing wide-field visual stimuli. We ask whether this pair of muscles acts as a muscle synergy (a single linear combination of activity) consistent with their hypothesized function of producing a left-right power differential. Alternatively, each muscle might individually encode variation in movement. We show that PLS feature analysis produces an efficient reduction of dimensionality in torque variation within a wingstroke. At first, the two muscles appear to behave as a synergy when we consider only their wingstroke-averaged torque. However, when we consider the PLS features, the muscles reveal independent encoding of torque. Using these features we can predictably reconstruct the variation in torque corresponding to changes in muscle activation. PLS-based feature analysis provides a general two-sided dimensionality reduction that reveals encoding in high dimensional

  4. Gene expression analysis of skin grafts and cultured keratinocytes using synthetic RNA normalization reveals insights into differentiation and growth control.

    Science.gov (United States)

    Katayama, Shintaro; Skoog, Tiina; Jouhilahti, Eeva-Mari; Siitonen, H Annika; Nuutila, Kristo; Tervaniemi, Mari H; Vuola, Jyrki; Johnsson, Anna; Lönnerberg, Peter; Linnarsson, Sten; Elomaa, Outi; Kankuri, Esko; Kere, Juha

    2015-06-25

    Keratinocytes (KCs) are the most frequent cells in the epidermis, and they are often isolated and cultured in vitro to study the molecular biology of the skin. Cultured primary cells and various immortalized cells have been frequently used as skin models but their comparability to intact skin has been questioned. Moreover, when analyzing KC transcriptomes, fluctuation of polyA+ RNA content during the KCs' lifecycle has been omitted. We performed STRT RNA sequencing on 10 ng samples of total RNA from three different sample types: i) epidermal tissue (split-thickness skin grafts), ii) cultured primary KCs, and iii) HaCaT cell line. We observed significant variation in cellular polyA+ RNA content between tissue and cell culture samples of KCs. The use of synthetic RNAs and SAMstrt in normalization enabled comparison of gene expression levels in the highly heterogenous samples and facilitated discovery of differences between the tissue samples and cultured cells. The transcriptome analysis sensitively revealed genes involved in KC differentiation in skin grafts and cell cycle regulation related genes in cultured KCs and emphasized the fluctuation of transcription factors and non-coding RNAs associated to sample types. The epidermal keratinocytes derived from tissue and cell culture samples showed highly different polyA+ RNA contents. The use of SAMstrt and synthetic RNA based normalization allowed the comparison between tissue and cell culture samples and thus proved to be valuable tools for RNA-seq analysis with translational approach. Transciptomics revealed clear difference both between tissue and cell culture samples and between primary KCs and immortalized HaCaT cells.

  5. Genetic control of environmental variation of two quantitative traits of Drosophila melanogaster revealed by whole-genome sequencing

    DEFF Research Database (Denmark)

    Sørensen, Peter; de los Campos, Gustavo; Morgante, Fabio

    2015-01-01

    and others more volatile performance. Understanding the mechanisms responsible for environmental variability not only informs medical questions but is relevant in evolution and in agricultural science. In this work fully sequenced inbred lines of Drosophila melanogaster were analyzed to study the nature...... of genetic control of environmental variance for two quantitative traits: starvation resistance (SR) and startle response (SL). The evidence for genetic control of environmental variance is compelling for both traits. Sequence information is incorporated in random regression models to study the underlying...... genetic signals, which are shown to be different in the two traits. Genomic variance in sexual dimorphism was found for SR but not for SL. Indeed, the proportion of variance captured by sequence information and the contribution to this variance from four chromosome segments differ between sexes in SR...

  6. RNA-Seq analysis of isolate- and growth phase-specific differences in the global transcriptomes of enteropathogenic Escherichia coli prototype isolates

    Science.gov (United States)

    Hazen, Tracy H.; Daugherty, Sean C.; Shetty, Amol; Mahurkar, Anup A.; White, Owen; Kaper, James B.; Rasko, David A.

    2015-01-01

    Enteropathogenic Escherichia coli (EPEC) are a leading cause of diarrheal illness among infants in developing countries. E. coli isolates classified as typical EPEC are identified by the presence of the locus of enterocyte effacement (LEE) and the bundle-forming pilus (BFP), and absence of the Shiga-toxin genes, while the atypical EPEC also encode LEE but do not encode BFP or Shiga-toxin. Comparative genomic analyses have demonstrated that EPEC isolates belong to diverse evolutionary lineages and possess lineage- and isolate-specific genomic content. To investigate whether this genomic diversity results in significant differences in global gene expression, we used an RNA sequencing (RNA-Seq) approach to characterize the global transcriptomes of the prototype typical EPEC isolates E2348/69, B171, C581-05, and the prototype atypical EPEC isolate E110019. The global transcriptomes were characterized during laboratory growth in two different media and three different growth phases, as well as during adherence of the EPEC isolates to human cells using in vitro tissue culture assays. Comparison of the global transcriptomes during these conditions was used to identify isolate- and growth phase-specific differences in EPEC gene expression. These analyses resulted in the identification of genes that encode proteins involved in survival and metabolism that were coordinately expressed with virulence factors. These findings demonstrate there are isolate- and growth phase-specific differences in the global transcriptomes of EPEC prototype isolates, and highlight the utility of comparative transcriptomics for identifying additional factors that are directly or indirectly involved in EPEC pathogenesis. PMID:26124752

  7. Scan-rescan reproducibility of segmental aortic wall shear stress as assessed by phase-specific segmentation with 4D flow MRI in healthy volunteers.

    Science.gov (United States)

    van der Palen, Roel L F; Roest, Arno A W; van den Boogaard, Pieter J; de Roos, Albert; Blom, Nico A; Westenberg, Jos J M

    2018-05-26

    The aim was to investigate scan-rescan reproducibility and observer variability of segmental aortic 3D systolic wall shear stress (WSS) by phase-specific segmentation with 4D flow MRI in healthy volunteers. Ten healthy volunteers (age 26.5 ± 2.6 years) underwent aortic 4D flow MRI twice. Maximum 3D systolic WSS (WSSmax) and mean 3D systolic WSS (WSSmean) for five thoracic aortic segments over five systolic cardiac phases by phase-specific segmentations were calculated. Scan-rescan analysis and observer reproducibility analysis were performed. Scan-rescan data showed overall good reproducibility for WSSmean (coefficient of variation, COV 10-15%) with moderate-to-strong intraclass correlation coefficient (ICC 0.63-0.89). The variability in WSSmax was high (COV 16-31%) with moderate-to-good ICC (0.55-0.79) for different aortic segments. Intra- and interobserver reproducibility was good-to-excellent for regional aortic WSSmax (ICC ≥ 0.78; COV ≤ 17%) and strong-to-excellent for WSSmean (ICC ≥ 0.86; COV ≤ 11%). In general, ascending aortic segments showed more WSSmax/WSSmean variability compared to aortic arch or descending aortic segments for scan-rescan, intraobserver and interobserver comparison. Scan-rescan reproducibility was good for WSSmean and moderate for WSSmax for all thoracic aortic segments over multiple systolic phases in healthy volunteers. Intra/interobserver reproducibility for segmental WSS assessment was good-to-excellent. Variability of WSSmax is higher and should be taken into account in case of individual follow-up or in comparative rest-stress studies to avoid misinterpretation.

  8. Analyses in zebrafish embryos reveal that nanotoxicity profiles are dependent on surface-functionalization controlled penetrance of biological membranes.

    Science.gov (United States)

    Paatero, Ilkka; Casals, Eudald; Niemi, Rasmus; Özliseli, Ezgi; Rosenholm, Jessica M; Sahlgren, Cecilia

    2017-08-21

    Mesoporous silica nanoparticles (MSNs) are extensively explored as drug delivery systems, but in depth understanding of design-toxicity relationships is still scarce. We used zebrafish (Danio rerio) embryos to study toxicity profiles of differently surface functionalized MSNs. Embryos with the chorion membrane intact, or dechoroniated embryos, were incubated or microinjected with amino (NH 2 -MSNs), polyethyleneimine (PEI-MSNs), succinic acid (SUCC-MSNs) or polyethyleneglycol (PEG-MSNs) functionalized MSNs. Toxicity was assessed by viability and cardiovascular function. NH 2 -MSNs, SUCC-MSNs and PEG-MSNs were well tolerated, 50 µg/ml PEI-MSNs induced 100% lethality 48 hours post fertilization (hpf). Dechoroniated embryos were more sensitive and 10 µg/ml PEI-MSNs reduced viability to 5% at 96hpf. Sensitivity to PEG- and SUCC-, but not NH 2 -MSNs, was also enhanced. Typically cardiovascular toxicity was evident prior to lethality. Confocal microscopy revealed that PEI-MSNs penetrated into the embryos whereas PEG-, NH2- and SUCC-MSNs remained aggregated on the skin surface. Direct exposure of inner organs by microinjecting NH 2 -MSNs and PEI-MSNs demonstrated that the particles displayed similar toxicity indicating that functionalization affects the toxicity profile by influencing penetrance through biological barriers. The data emphasize the need for careful analyses of toxicity mechanisms in relevant models and constitute an important knowledge step towards the development of safer and sustainable nanotherapies.

  9. A pan-European epidemiological study reveals honey bee colony survival depends on beekeeper education and disease control.

    Directory of Open Access Journals (Sweden)

    Antoine Jacques

    Full Text Available Reports of honey bee population decline has spurred many national efforts to understand the extent of the problem and to identify causative or associated factors. However, our collective understanding of the factors has been hampered by a lack of joined up trans-national effort. Moreover, the impacts of beekeeper knowledge and beekeeping management practices have often been overlooked, despite honey bees being a managed pollinator. Here, we established a standardised active monitoring network for 5 798 apiaries over two consecutive years to quantify honey bee colony mortality across 17 European countries. Our data demonstrate that overwinter losses ranged between 2% and 32%, and that high summer losses were likely to follow high winter losses. Multivariate Poisson regression models revealed that hobbyist beekeepers with small apiaries and little experience in beekeeping had double the winter mortality rate when compared to professional beekeepers. Furthermore, honey bees kept by professional beekeepers never showed signs of disease, unlike apiaries from hobbyist beekeepers that had symptoms of bacterial infection and heavy Varroa infestation. Our data highlight beekeeper background and apicultural practices as major drivers of honey bee colony losses. The benefits of conducting trans-national monitoring schemes and improving beekeeper training are discussed.

  10. Mutational studies reveal a complex set of positive and negative control elements within the chicken vitellogenin II promoter.

    Science.gov (United States)

    Seal, S N; Davis, D L; Burch, J B

    1991-05-01

    The endogenous chicken vitellogenin II (VTGII) gene is transcribed exclusively in hepatocytes in response to estrogen. We previously identified two estrogen response elements (EREs) upstream of this gene. We now present an analysis of the VTGII promoter activated by these EREs in response to estrogen. Chimeric VTGII-CAT genes were cotransfected into LMH chicken hepatoma cells along with an estrogen receptor expression vector, and transient CAT expression was assayed after culturing the cells in the absence or presence of estrogen. An analysis of constructs bearing deletions downstream of the more proximal ERE indicated that promoter elements relevant to transcription in LMH cells extend to between -113 and -96. The relative importance of sequences within the VTGII promoter was examined by using 10 contiguous linker scanner mutations spanning the region from -117 to -24. Although most of these mutations compromised VTGII promoter function, one dramatically increased expression in LMH cells and also rendered the VTGII promoter capable of being activated by cis-linked EREs in fibroblasts cotransfected with an estrogen receptor expression vector. Gel retardation and DNase I footprinting assays revealed four factor-binding sites within this promoter. We demonstrate that three of these sites bind C/EBP, SP1, and USF (or related factors), respectively; the fourth site binds a factor that we denote TF-V beta. The biological relevance of these findings is suggested by the fact that three of these binding sites map to sites previously shown to be occupied in vivo in response to estrogen.

  11. Automatic and Controlled Semantic Retrieval: TMS Reveals Distinct Contributions of Posterior Middle Temporal Gyrus and Angular Gyrus.

    Science.gov (United States)

    Davey, James; Cornelissen, Piers L; Thompson, Hannah E; Sonkusare, Saurabh; Hallam, Glyn; Smallwood, Jonathan; Jefferies, Elizabeth

    2015-11-18

    Semantic retrieval involves both (1) automatic spreading activation between highly related concepts and (2) executive control processes that tailor this activation to suit the current context or goals. Two structures in left temporoparietal cortex, angular gyrus (AG) and posterior middle temporal gyrus (pMTG), are thought to be crucial to semantic retrieval and are often recruited together during semantic tasks; however, they show strikingly different patterns of functional connectivity at rest (coupling with the "default mode network" and "frontoparietal control system," respectively). Here, transcranial magnetic stimulation (TMS) was used to establish a causal yet dissociable role for these sites in semantic cognition in human volunteers. TMS to AG disrupted thematic judgments particularly when the link between probe and target was strong (e.g., a picture of an Alsatian with a bone), and impaired the identification of objects at a specific but not a superordinate level (for the verbal label "Alsatian" not "animal"). In contrast, TMS to pMTG disrupted thematic judgments for weak but not strong associations (e.g., a picture of an Alsatian with razor wire), and impaired identity matching for both superordinate and specific-level labels. Thus, stimulation to AG interfered with the automatic retrieval of specific concepts from the semantic store while stimulation of pMTG impaired semantic cognition when there was a requirement to flexibly shape conceptual activation in line with the task requirements. These results demonstrate that AG and pMTG make a dissociable contribution to automatic and controlled aspects of semantic retrieval. We demonstrate a novel functional dissociation between the angular gyrus (AG) and posterior middle temporal gyrus (pMTG) in conceptual processing. These sites are often coactivated during neuroimaging studies using semantic tasks, but their individual contributions are unclear. Using transcranial magnetic stimulation and tasks designed to

  12. Cold quantum-controlled rotationally inelastic scattering of HD with H2 and D2 reveals collisional partner reorientation

    Science.gov (United States)

    Perreault, William E.; Mukherjee, Nandini; Zare, Richard N.

    2018-05-01

    Molecular interactions are best probed by scattering experiments. Interpretation of these studies has been limited by lack of control over the quantum states of the incoming collision partners. We report here the rotationally inelastic collisions of quantum-state prepared deuterium hydride (HD) with H2 and D2 using a method that provides an improved control over the input states. HD was coexpanded with its partner in a single supersonic beam, which reduced the collision temperature to 0-5 K, and thereby restricted the involved incoming partial waves to s and p. By preparing HD with its bond axis preferentially aligned parallel and perpendicular to the relative velocity of the colliding partners, we observed that the rotational relaxation of HD depends strongly on the initial bond-axis orientation. We developed a partial-wave analysis that conclusively demonstrates that the scattering mechanism involves the exchange of internal angular momentum between the colliding partners. The striking differences between H2/HD and D2/HD scattering suggest the presence of anisotropically sensitive resonances.

  13. Structure-guided investigation of lipopolysaccharide O-antigen chain length regulators reveals regions critical for modal length control.

    Science.gov (United States)

    Kalynych, Sergei; Ruan, Xiang; Valvano, Miguel A; Cygler, Miroslaw

    2011-08-01

    The O-antigen component of the lipopolysaccharide (LPS) represents a population of polysaccharide molecules with nonrandom (modal) chain length distribution. The number of the repeat O units in each individual O-antigen polymer depends on the Wzz chain length regulator, an inner membrane protein belonging to the polysaccharide copolymerase (PCP) family. Different Wzz proteins confer vastly different ranges of modal lengths (4 to >100 repeat units), despite having remarkably conserved structural folds. The molecular mechanism responsible for the selective preference for a certain number of O units is unknown. Guided by the three-dimensional structures of PCPs, we constructed a panel of chimeric molecules containing parts of two closely related Wzz proteins from Salmonella enterica and Shigella flexneri which confer different O-antigen chain length distributions. Analysis of the O-antigen length distribution imparted by each chimera revealed the region spanning amino acids 67 to 95 (region 67 to 95), region 200 to 255, and region 269 to 274 as primarily affecting the length distribution. We also showed that there is no synergy between these regions. In particular, region 269 to 274 also influenced chain length distribution mediated by two distantly related PCPs, WzzB and FepE. Furthermore, from the 3 regions uncovered in this study, region 269 to 274 appeared to be critical for the stability of the oligomeric form of Wzz, as determined by cross-linking experiments. Together, our data suggest that chain length determination depends on regions that likely contribute to stabilize a supramolecular complex.

  14. Phase dependence of transport-aperture coordination variability reveals control strategy of reach-to-grasp movements.

    Science.gov (United States)

    Rand, Miya K; Shimansky, Y P; Hossain, Abul B M I; Stelmach, George E

    2010-11-01

    Based on an assumption of movement control optimality in reach-to-grasp movements, we have recently developed a mathematical model of transport-aperture coordination (TAC), according to which the hand-target distance is a function of hand velocity and acceleration, aperture magnitude, and aperture velocity and acceleration (Rand et al. in Exp Brain Res 188:263-274, 2008). Reach-to-grasp movements were performed by young adults under four different reaching speeds and two different transport distances. The residual error magnitude of fitting the above model to data across different trials and subjects was minimal for the aperture-closure phase, but relatively much greater for the aperture-opening phase, indicating considerable difference in TAC variability between those phases. This study's goal is to identify the main reasons for that difference and obtain insights into the control strategy of reach-to-grasp movements. TAC variability within the aperture-opening phase of a single trial was found minimal, indicating that TAC variability between trials was not due to execution noise, but rather a result of inter-trial and inter-subject variability of motor plan. At the same time, the dependence of the extent of trial-to-trial variability of TAC in that phase on the speed of hand transport was sharply inconsistent with the concept of speed-accuracy trade-off: the lower the speed, the larger the variability. Conversely, the dependence of the extent of TAC variability in the aperture-closure phase on hand transport speed was consistent with that concept. Taking into account recent evidence that the cost of neural information processing is substantial for movement planning, the dependence of TAC variability in the aperture-opening phase on task performance conditions suggests that it is not the movement time that the CNS saves in that phase, but the cost of neuro-computational resources and metabolic energy required for TAC regulation in that phase. Thus, the CNS

  15. Comprehensive Definition of the SigH Regulon of Mycobacterium tuberculosis Reveals Transcriptional Control of Diverse Stress Responses.

    Directory of Open Access Journals (Sweden)

    Jared D Sharp

    Full Text Available Expression of SigH, one of 12 Mycobacterium tuberculosis alternative sigma factors, is induced by heat, oxidative and nitric oxide stresses. SigH activation has been shown to increase expression of several genes, including genes involved in maintaining redox equilibrium and in protein degradation. However, few of these are known to be directly regulated by SigH. The goal of this project is to comprehensively define the Mycobacterium tuberculosis genes and operons that are directly controlled by SigH in order to gain insight into the role of SigH in regulating M. tuberculosis physiology. We used ChIP-Seq to identify in vivo SigH binding sites throughout the M. tuberculosis genome, followed by quantification of SigH-dependent expression of genes linked to these sites and identification of SigH-regulated promoters. We identified 69 SigH binding sites, which are located both in intergenic regions and within annotated coding sequences in the annotated M. tuberculosis genome. 41 binding sites were linked to genes that showed greater expression following heat stress in a SigH-dependent manner. We identified several genes not previously known to be regulated by SigH, including genes involved in DNA repair, cysteine biosynthesis, translation, and genes of unknown function. Experimental and computational analysis of SigH-regulated promoter sequences within these binding sites identified strong consensus -35 and -10 promoter sequences, but with tolerance for non-consensus bases at specific positions. This comprehensive identification and validation of SigH-regulated genes demonstrates an extended SigH regulon that controls an unexpectedly broad range of stress response functions.

  16. Comprehensive Definition of the SigH Regulon of Mycobacterium tuberculosis Reveals Transcriptional Control of Diverse Stress Responses.

    Science.gov (United States)

    Sharp, Jared D; Singh, Atul K; Park, Sang Tae; Lyubetskaya, Anna; Peterson, Matthew W; Gomes, Antonio L C; Potluri, Lakshmi-Prasad; Raman, Sahadevan; Galagan, James E; Husson, Robert N

    2016-01-01

    Expression of SigH, one of 12 Mycobacterium tuberculosis alternative sigma factors, is induced by heat, oxidative and nitric oxide stresses. SigH activation has been shown to increase expression of several genes, including genes involved in maintaining redox equilibrium and in protein degradation. However, few of these are known to be directly regulated by SigH. The goal of this project is to comprehensively define the Mycobacterium tuberculosis genes and operons that are directly controlled by SigH in order to gain insight into the role of SigH in regulating M. tuberculosis physiology. We used ChIP-Seq to identify in vivo SigH binding sites throughout the M. tuberculosis genome, followed by quantification of SigH-dependent expression of genes linked to these sites and identification of SigH-regulated promoters. We identified 69 SigH binding sites, which are located both in intergenic regions and within annotated coding sequences in the annotated M. tuberculosis genome. 41 binding sites were linked to genes that showed greater expression following heat stress in a SigH-dependent manner. We identified several genes not previously known to be regulated by SigH, including genes involved in DNA repair, cysteine biosynthesis, translation, and genes of unknown function. Experimental and computational analysis of SigH-regulated promoter sequences within these binding sites identified strong consensus -35 and -10 promoter sequences, but with tolerance for non-consensus bases at specific positions. This comprehensive identification and validation of SigH-regulated genes demonstrates an extended SigH regulon that controls an unexpectedly broad range of stress response functions.

  17. Monitoring Spongospora subterranea Development in Potato Roots Reveals Distinct Infection Patterns and Enables Efficient Assessment of Disease Control Methods.

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    Tamilarasan Thangavel

    Full Text Available Spongospora subterranea is responsible for significant potato root and tuber disease globally. Study of this obligate (non-culturable pathogen that infects below-ground plant parts is technically difficult. The capacity to measure the dynamics and patterns of root infections can greatly assist in determining the efficacy of control treatments on disease progression. This study used qPCR and histological analysis in time-course experiments to measure temporal patterns of pathogen multiplication and disease development in potato (and tomato roots and tubers. Effects of delayed initiation of infection and fungicidal seed tuber and soil treatments were assessed. This study found roots at all plant developmental ages were susceptible to infection but that delaying infection significantly reduced pathogen content and resultant disease at final harvest. The pathogen was first detected in roots 15-20 days after inoculation (DAI and the presence of zoosporangia noted 15-45 DAI. Following initial infection pathogen content in roots increased at a similar rate regardless of plant age at inoculation. All fungicide treatments (except soil-applied mancozeb which had a variable response suppressed pathogen multiplication and root and tuber disease. In contrast to delayed inoculation, the fungicide treatments slowed disease progress (rate rather than delaying onset of infection. Trials under suboptimal temperatures for disease expression provided valuable data on root infection rate, demonstrating the robustness of monitoring root infection. These results provide an early measure of the efficacy of control treatments and indicate two possible patterns of disease suppression by either delayed initiation of infection which then proceeds at a similar rate or diminished epidemic rate.

  18. A closer look at cognitive control: Differences in resource allocation during updating, inhibition and switching as revealed by pupillometry

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    Eefje eRondeel

    2015-09-01

    Full Text Available The present study investigated resource allocation, as measured by pupil dilation, in tasks measuring updating (2-Back task, inhibition (Stroop task and switching (Number Switch task. Because each cognitive control component has unique characteristics, differences in patterns of resource allocation were expected. Pupil and behavioral data from 35 participants were analysed. In the 2-Back task (requiring correct matching of current stimulus identity at trial p with the stimulus two trials back, p-2 we found that better performance (low total of errors made in the task was positively correlated to the mean pupil dilation during correctly responding to targets. In the Stroop task, pupil dilation on incongruent trials was higher than those on congruent trials. Incongruent versus congruent trial pupil dilation differences were positively related to reaction time differences between incongruent and congruent trials. Furthermore, on congruent Stroop trials, pupil dilation was negatively related to reaction times, presumably because more effort allocation paid off in terms of faster responses. In addition, pupil dilation on correctly-responded-to congruent trials predicted a weaker Stroop interference effect in terms of errors, probably because pupil dilation on congruent trials were diagnostic of task motivation, resulting in better performance. In the Number Switch task we found higher pupil dilation in switch as compared to non-switch trials. On the Number Switch task, pupil dilation was not related to performance. We also explored error-related pupil dilation in all tasks. The results provide new insights in the diversity of the cognitive control components in terms of resource allocation as a function of individual differences, task difficulty and error processing.

  19. Novel diffusion tensor imaging technique reveals developmental streamline volume changes in the corticospinal tract associated with leg motor control.

    Science.gov (United States)

    Kamson, David O; Juhász, Csaba; Chugani, Harry T; Jeong, Jeong-Won

    2015-04-01

    Diffusion tensor imaging (DTI) has expanded our knowledge of corticospinal tract (CST) anatomy and development. However, previous developmental DTI studies assessed the CST as a whole, overlooking potential differences in development of its components related to control of the upper and lower extremities. The present cross-sectional study investigated age-related changes, side and gender differences in streamline volume of the leg- and hand-related segments of the CST in children. DTI data of 31 children (1-14 years; mean age: 6±4 years; 17 girls) with normal conventional MRI were analyzed. Leg- and hand-related CST streamline volumes were quantified separately, using a recently validated novel tractography approach. CST streamline volumes on both sides were compared between genders and correlated with age. Higher absolute streamline volumes were found in the left leg-related CST compared to the right (p=0.001) without a gender effect (p=0.4), whereas no differences were found in the absolute hand-related CST volumes (p>0.4). CST leg-related streamline volumes, normalized to hemispheric white matter volumes, declined with age in the right hemisphere only (R=-.51; p=0.004). Absolute leg-related CST streamline volumes showed similar, but slightly weaker correlations. Hand-related absolute or normalized CST streamline volumes showed no age-related variations on either side. These results suggest differential development of CST segments controlling hand vs. leg movements. Asymmetric volume changes in the lower limb motor pathway may be secondary to gradually strengthening left hemispheric dominance and is consistent with previous data suggesting that footedness is a better predictor of hemispheric lateralization than handedness. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  20. Monitoring Spongospora subterranea Development in Potato Roots Reveals Distinct Infection Patterns and Enables Efficient Assessment of Disease Control Methods.

    Science.gov (United States)

    Thangavel, Tamilarasan; Tegg, Robert S; Wilson, Calum R

    2015-01-01

    Spongospora subterranea is responsible for significant potato root and tuber disease globally. Study of this obligate (non-culturable) pathogen that infects below-ground plant parts is technically difficult. The capacity to measure the dynamics and patterns of root infections can greatly assist in determining the efficacy of control treatments on disease progression. This study used qPCR and histological analysis in time-course experiments to measure temporal patterns of pathogen multiplication and disease development in potato (and tomato) roots and tubers. Effects of delayed initiation of infection and fungicidal seed tuber and soil treatments were assessed. This study found roots at all plant developmental ages were susceptible to infection but that delaying infection significantly reduced pathogen content and resultant disease at final harvest. The pathogen was first detected in roots 15-20 days after inoculation (DAI) and the presence of zoosporangia noted 15-45 DAI. Following initial infection pathogen content in roots increased at a similar rate regardless of plant age at inoculation. All fungicide treatments (except soil-applied mancozeb which had a variable response) suppressed pathogen multiplication and root and tuber disease. In contrast to delayed inoculation, the fungicide treatments slowed disease progress (rate) rather than delaying onset of infection. Trials under suboptimal temperatures for disease expression provided valuable data on root infection rate, demonstrating the robustness of monitoring root infection. These results provide an early measure of the efficacy of control treatments and indicate two possible patterns of disease suppression by either delayed initiation of infection which then proceeds at a similar rate or diminished epidemic rate.

  1. N-terminomics reveals control of Arabidopsis seed storage proteins and proteases by the Arg/N-end rule pathway.

    Science.gov (United States)

    Zhang, Hongtao; Gannon, Lucy; Hassall, Kirsty L; Deery, Michael J; Gibbs, Daniel J; Holdsworth, Michael J; van der Hoorn, Renier A L; Lilley, Kathryn S; Theodoulou, Frederica L

    2018-05-01

    The N-end rule pathway of targeted protein degradation is an important regulator of diverse processes in plants but detailed knowledge regarding its influence on the proteome is lacking. To investigate the impact of the Arg/N-end rule pathway on the proteome of etiolated seedlings, we used terminal amine isotopic labelling of substrates with tandem mass tags (TMT-TAILS) for relative quantification of N-terminal peptides in prt6, an Arabidopsis thaliana N-end rule mutant lacking the E3 ligase PROTEOLYSIS6 (PRT6). TMT-TAILS identified over 4000 unique N-terminal peptides representing c. 2000 protein groups. Forty-five protein groups exhibited significantly increased N-terminal peptide abundance in prt6 seedlings, including cruciferins, major seed storage proteins, which were regulated by Group VII Ethylene Response Factor (ERFVII) transcription factors, known substrates of PRT6. Mobilisation of endosperm α-cruciferin was delayed in prt6 seedlings. N-termini of several proteases were downregulated in prt6, including RD21A. RD21A transcript, protein and activity levels were downregulated in a largely ERFVII-dependent manner. By contrast, cathepsin B3 protein and activity were upregulated by ERFVIIs independent of transcript. We propose that the PRT6 branch of the pathway regulates protease activities in a complex manner and optimises storage reserve mobilisation in the transition from seed to seedling via control of ERFVII action. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  2. Amyloid domains in the cell nucleus controlled by nucleoskeletal protein lamin B1 reveal a new pathway of mercury neurotoxicity

    Science.gov (United States)

    Arnhold, Florian; Gührs, Karl-Heinz

    2015-01-01

    Mercury (Hg) is a bioaccumulating trace metal that globally circulates the atmosphere and waters in its elemental, inorganic and organic chemical forms. While Hg represents a notorious neurotoxicant, the underlying cellular pathways are insufficiently understood. We identify amyloid protein aggregation in the cell nucleus as a novel pathway of Hg-bio-interactions. By mass spectrometry of purified protein aggregates, a subset of spliceosomal components and nucleoskeletal protein lamin B1 were detected as constituent parts of an Hg-induced nuclear aggregome network. The aggregome network was located by confocal imaging of amyloid-specific antibodies and dyes to amyloid cores within splicing-speckles that additionally recruit components of the ubiquitin-proteasome system. Hg significantly enhances global proteasomal activity in the nucleus, suggesting that formation of amyloid speckles plays a role in maintenance of protein homeostasis. RNAi knock down showed that lamin B1 for its part regulates amyloid speckle formation and thus likewise participates in nuclear protein homeostasis. As the Hg-induced cascade of interactions between the nucleoskeleton and protein homeostasis reduces neuronal signalling, amyloid fibrillation in the cell nucleus is introduced as a feature of Hg-neurotoxicity that opens new avenues of future research. Similar to protein aggregation events in the cytoplasm that are controlled by the cytoskeleton, amyloid fibrillation of nuclear proteins may be driven by the nucleoskeleton. PMID:25699204

  3. First Mitochondrial Genome from Nemouridae (Plecoptera) Reveals Novel Features of the Elongated Control Region and Phylogenetic Implications.

    Science.gov (United States)

    Chen, Zhi-Teng; Du, Yu-Zhou

    2017-05-05

    The complete mitochondrial genome (mitogenome) of Nemoura nankinensis (Plecoptera: Nemouridae) was sequenced as the first reported mitogenome from the family Nemouridae. The N. nankinensis mitogenome was the longest (16,602 bp) among reported plecopteran mitogenomes, and it contains 37 genes including 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes and two ribosomal RNA (rRNA) genes. Most PCGs used standard ATN as start codons, and TAN as termination codons. All tRNA genes of N. nankinensis could fold into the cloverleaf secondary structures except for trnSer ( AGN ), whose dihydrouridine (DHU) arm was reduced to a small loop. There was also a large non-coding region (control region, CR) in the N. nankinensis mitogenome. The 1751 bp CR was the longest and had the highest A+T content (81.8%) among stoneflies. A large tandem repeat region, five potential stem-loop (SL) structures, four tRNA-like structures and four conserved sequence blocks (CSBs) were detected in the elongated CR. The presence of these tRNA-like structures in the CR has never been reported in other plecopteran mitogenomes. These novel features of the elongated CR in N. nankinensis may have functions associated with the process of replication and transcription. Finally, phylogenetic reconstruction suggested that Nemouridae was the sister-group of Capniidae.

  4. Sample Entropy and Traditional Measures of Heart Rate Dynamics Reveal Different Modes of Cardiovascular Control During Low Intensity Exercise

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    Matthias Weippert

    2014-10-01

    Full Text Available Nonlinear parameters of heart rate variability (HRV have proven their prognostic value in clinical settings, but their physiological background is not very well established. We assessed the effects of low intensity isometric (ISO and dynamic (DYN exercise of the lower limbs on heart rate matched intensity on traditional and entropy measures of HRV. Due to changes of afferent feedback under DYN and ISO a distinct autonomic response, mirrored by HRV measures, was hypothesized. Five-minute inter-beat interval measurements of 43 healthy males (26.0 ± 3.1 years were performed during rest, DYN and ISO in a randomized order. Blood pressures and rate pressure product were higher during ISO vs. DYN (p < 0.001. HRV indicators SDNN as well as low and high frequency power were significantly higher during ISO (p < 0.001 for all measures. Compared to DYN, sample entropy (SampEn was lower during ISO (p < 0.001. Concluding, contraction mode itself is a significant modulator of the autonomic cardiovascular response to exercise. Compared to DYN, ISO evokes a stronger blood pressure response and an enhanced interplay between both autonomic branches. Non-linear HRV measures indicate a more regular behavior under ISO. Results support the view of the reciprocal antagonism being only one of many modes of autonomic heart rate control. Under different conditions; the identical “end product” heart rate might be achieved by other modes such as sympathovagal co-activation as well.

  5. Body representations in the human brain revealed by kinesthetic illusions and their essential contributions to motor control and corporeal awareness.

    Science.gov (United States)

    Naito, Eiichi; Morita, Tomoyo; Amemiya, Kaoru

    2016-03-01

    The human brain can generate a continuously changing postural model of our body. Somatic (proprioceptive) signals from skeletal muscles and joints contribute to the formation of the body representation. Recent neuroimaging studies of proprioceptive bodily illusions have elucidated the importance of three brain systems (motor network, specialized parietal systems, right inferior fronto-parietal network) in the formation of the human body representation. The motor network, especially the primary motor cortex, processes afferent input from skeletal muscles. Such information may contribute to the formation of kinematic/dynamic postural models of limbs, thereby enabling fast online feedback control. Distinct parietal regions appear to play specialized roles in the transformation/integration of information across different coordinate systems, which may subserve the adaptability and flexibility of the body representation. Finally, the right inferior fronto-parietal network, connected by the inferior branch of the superior longitudinal fasciculus, is consistently recruited when an individual experiences various types of bodily illusions and its possible roles relate to corporeal awareness, which is likely elicited through a series of neuronal processes of monitoring and accumulating bodily information and updating the body representation. Because this network is also recruited when identifying one's own features, the network activity could be a neuronal basis for self-consciousness. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  6. A screen for constituents of motor control and decision making in Drosophila reveals visual distance-estimation neurons

    Science.gov (United States)

    Triphan, Tilman; Nern, Aljoscha; Roberts, Sonia F.; Korff, Wyatt; Naiman, Daniel Q.; Strauss, Roland

    2016-01-01

    Climbing over chasms larger than step size is vital to fruit flies, since foraging and mating are achieved while walking. Flies avoid futile climbing attempts by processing parallax-motion vision to estimate gap width. To identify neuronal substrates of climbing control, we screened a large collection of fly lines with temporarily inactivated neuronal populations in a novel high-throughput assay described here. The observed climbing phenotypes were classified; lines in each group are reported. Selected lines were further analysed by high-resolution video cinematography. One striking class of flies attempts to climb chasms of unsurmountable width; expression analysis guided us to C2 optic-lobe interneurons. Inactivation of C2 or the closely related C3 neurons with highly specific intersectional driver lines consistently reproduced hyperactive climbing whereas strong or weak artificial depolarization of C2/C3 neurons strongly or mildly decreased climbing frequency. Contrast-manipulation experiments support our conclusion that C2/C3 neurons are part of the distance-evaluation system. PMID:27255169

  7. Novel targets of the CbrAB/Crc carbon catabolite control system revealed by transcript abundance in Pseudomonas aeruginosa.

    Science.gov (United States)

    Sonnleitner, Elisabeth; Valentini, Martina; Wenner, Nicolas; Haichar, Feth el Zahar; Haas, Dieter; Lapouge, Karine

    2012-01-01

    The opportunistic human pathogen Pseudomonas aeruginosa is able to utilize a wide range of carbon and nitrogen compounds, allowing it to grow in vastly different environments. The uptake and catabolism of growth substrates are organized hierarchically by a mechanism termed catabolite repression control (Crc) whereby the Crc protein establishes translational repression of target mRNAs at CA (catabolite activity) motifs present in target mRNAs near ribosome binding sites. Poor carbon sources lead to activation of the CbrAB two-component system, which induces transcription of the small RNA (sRNA) CrcZ. This sRNA relieves Crc-mediated repression of target mRNAs. In this study, we have identified novel targets of the CbrAB/Crc system in P. aeruginosa using transcriptome analysis in combination with a search for CA motifs. We characterized four target genes involved in the uptake and utilization of less preferred carbon sources: estA (secreted esterase), acsA (acetyl-CoA synthetase), bkdR (regulator of branched-chain amino acid catabolism) and aroP2 (aromatic amino acid uptake protein). Evidence for regulation by CbrAB, CrcZ and Crc was obtained in vivo using appropriate reporter fusions, in which mutation of the CA motif resulted in loss of catabolite repression. CbrB and CrcZ were important for growth of P. aeruginosa in cystic fibrosis (CF) sputum medium, suggesting that the CbrAB/Crc system may act as an important regulator during chronic infection of the CF lung.

  8. Arabidopsis mutant sk156 reveals complex regulation of SPL15 in a miR156-controlled gene network.

    Science.gov (United States)

    Wei, Shu; Gruber, Margaret Y; Yu, Bianyun; Gao, Ming-Jun; Khachatourians, George G; Hegedus, Dwayne D; Parkin, Isobel A P; Hannoufa, Abdelali

    2012-09-18

    The Arabidopsis microRNA156 (miR156) regulates 11 members of the SQUAMOSA PROMOTER BINDING PROTEIN LIKE (SPL) family by base pairing to complementary target mRNAs. Each SPL gene further regulates a set of other genes; thus, miR156 controls numerous genes through a complex gene regulation network. Increased axillary branching occurs in transgenic Arabidopsis overexpressing miR156b, similar to that observed in loss-of-function max3 and max4 mutants with lesions in carotenoid cleavage dioxygenases. Arabidopsis miR156b was found to enhance carotenoid levels and reproductive shoot branching when expressed in Brassica napus, suggesting a link between miR156b expression and carotenoid metabolism. However, details of the miR156 regulatory network of SPL genes related to carotenoid metabolism are not known. In this study, an Arabidopsis T-DNA enhancer mutant, sk156, was identified due to its altered branching and trichome morphology and increased seed carotenoid levels compared to wild type (WT) ecovar Columbia. Enhanced miR156b expression due to the 35S enhancers present on the T-DNA insert was responsible for these phenotypes. Constitutive and leaf primodium-specific expression of a miR156-insensitive (mutated) SPL15 (SPL15m) largely restored WT seed carotenoid levels and plant morphology when expressed in sk156. The Arabidopsis native miR156-sensitive SPL15 (SPL15n) and SPL15m driven by a native SPL15 promoter did not restore the WT phenotype in sk156. Our findings suggest that SPL15 function is somewhat redundant with other SPL family members, which collectively affect plant phenotypes. Moreover, substantially decreased miR156b transcript levels in sk156 expressing SPL15m, together with the presence of multiple repeats of SPL-binding GTAC core sequence close to the miR156b transcription start site, suggested feedback regulation of miR156b expression by SPL15. This was supported by the demonstration of specific in vitro interaction between DNA-binding SBP domain of SPL15

  9. Arabidopsis mutant sk156 reveals complex regulation of SPL15 in a miR156-controlled gene network

    Directory of Open Access Journals (Sweden)

    Wei Shu

    2012-09-01

    Full Text Available Abstract Background The Arabidopsis microRNA156 (miR156 regulates 11 members of the SQUAMOSA PROMOTER BINDING PROTEIN LIKE (SPL family by base pairing to complementary target mRNAs. Each SPL gene further regulates a set of other genes; thus, miR156 controls numerous genes through a complex gene regulation network. Increased axillary branching occurs in transgenic Arabidopsis overexpressing miR156b, similar to that observed in loss-of-function max3 and max4 mutants with lesions in carotenoid cleavage dioxygenases. Arabidopsis miR156b was found to enhance carotenoid levels and reproductive shoot branching when expressed in Brassica napus, suggesting a link between miR156b expression and carotenoid metabolism. However, details of the miR156 regulatory network of SPL genes related to carotenoid metabolism are not known. Results In this study, an Arabidopsis T-DNA enhancer mutant, sk156, was identified due to its altered branching and trichome morphology and increased seed carotenoid levels compared to wild type (WT ecovar Columbia. Enhanced miR156b expression due to the 35S enhancers present on the T-DNA insert was responsible for these phenotypes. Constitutive and leaf primodium-specific expression of a miR156-insensitive (mutated SPL15 (SPL15m largely restored WT seed carotenoid levels and plant morphology when expressed in sk156. The Arabidopsis native miR156-sensitive SPL15 (SPL15n and SPL15m driven by a native SPL15 promoter did not restore the WT phenotype in sk156. Our findings suggest that SPL15 function is somewhat redundant with other SPL family members, which collectively affect plant phenotypes. Moreover, substantially decreased miR156b transcript levels in sk156 expressing SPL15m, together with the presence of multiple repeats of SPL-binding GTAC core sequence close to the miR156b transcription start site, suggested feedback regulation of miR156b expression by SPL15. This was supported by the demonstration of specific in vitro

  10. Metabolome analysis reveals the effect of carbon catabolite control on the poly(γ-glutamic acid) biosynthesis of Bacillus licheniformis ATCC 9945.

    Science.gov (United States)

    Mitsunaga, Hitoshi; Meissner, Lena; Palmen, Thomas; Bamba, Takeshi; Büchs, Jochen; Fukusaki, Eiichiro

    2016-04-01

    Poly(γ-glutamic acid) (PGA) is a polymer composed of L- and/or D-glutamic acids that is produced by Bacillus sp. Because the polymer has various features as water soluble, edible, non-toxic and so on, it has attracted attention as a candidate for many applications such as foods, cosmetics and so on. However, although it is well known that the intracellular metabolism of Bacillus sp. is mainly regulated by catabolite control, the effect of the catabolite control on the PGA producing Bacillus sp. is largely unknown. This study is the first report of metabolome analysis on the PGA producing Bacillus sp. that reveals the effect of carbon catabolite control on the metabolism of PGA producing Bacillus licheniformis ATCC 9945. Results showed that the cells cultivated in glycerol-containing medium showed higher PGA production than the cells in glucose-containing medium. Furthermore, metabolome analysis revealed that the activators of CcpA and CodY, global regulatory proteins of the intracellular metabolism, accumulated in the cells cultivated in glycerol-containing and glucose-containing medium, respectively, with CodY apparently inhibiting PGA production. Moreover, the cells seemed to produce glutamate from citrate and ammonium using glutamine synthetase/glutamate synthase. Pulsed addition of di-ammonium hydrogen citrate, as suggested by the metabolome result, was able to achieve the highest value so far for PGA production in B. licheniformis. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  11. Mathematics revealed

    CERN Document Server

    Berman, Elizabeth

    1979-01-01

    Mathematics Revealed focuses on the principles, processes, operations, and exercises in mathematics.The book first offers information on whole numbers, fractions, and decimals and percents. Discussions focus on measuring length, percent, decimals, numbers as products, addition and subtraction of fractions, mixed numbers and ratios, division of fractions, addition, subtraction, multiplication, and division. The text then examines positive and negative numbers and powers and computation. Topics include division and averages, multiplication, ratios, and measurements, scientific notation and estim

  12. Age-dependent transition from cell-level to population-level control in murine intestinal homeostasis revealed by coalescence analysis.

    Directory of Open Access Journals (Sweden)

    Zheng Hu

    Full Text Available In multi-cellular organisms, tissue homeostasis is maintained by an exquisite balance between stem cell proliferation and differentiation. This equilibrium can be achieved either at the single cell level (a.k.a. cell asymmetry, where stem cells follow strict asymmetric divisions, or the population level (a.k.a. population asymmetry, where gains and losses in individual stem cell lineages are randomly distributed, but the net effect is homeostasis. In the mature mouse intestinal crypt, previous evidence has revealed a pattern of population asymmetry through predominantly symmetric divisions of stem cells. In this work, using population genetic theory together with previously published crypt single-cell data obtained at different mouse life stages, we reveal a strikingly dynamic pattern of stem cell homeostatic control. We find that single-cell asymmetric divisions are gradually replaced by stochastic population-level asymmetry as the mouse matures to adulthood. This lifelong process has important developmental and evolutionary implications in understanding how adult tissues maintain their homeostasis integrating the trade-off between intrinsic and extrinsic regulations.

  13. A Case–control and a family-based association study revealing an association between CYP2E1 polymorphisms and nasopharyngeal carcinoma risk in Cantonese

    Science.gov (United States)

    Jia, Wei-Hua; Pan, Qing-Hua; Qin, Hai-De; Xu, Ya-Fei; Shen, Guo-Ping; Chen, Lina; Chen, Li-Zhen; Feng, Qi-Sheng; Hong, Ming-Huang; Zeng, Yi-Xin; Shugart, Yin Yao

    2009-01-01

    Nasopharyngeal carcinoma (NPC) is rare in most parts of the world but is more prevalent in Southern China, especially in Guangdong. The cytochrome P450 2E1 (CYP2E1) has been recognized as one of the critically important enzymes involved in oxidizing carcinogens and is probably to be associated with NPC carcinogenesis. To systematically investigate the association between genetic variants in CYP2E1 and NPC risk in Cantonese, two independent studies, a family-based association study and a case–control study, were conducted using the haplotype-tagging single-nucleotide polymorphism approach. A total of 2499 individuals from 546 nuclear families were initially genotyped for the family-based association study. Single-nucleotide polymorphisms (SNPs) rs9418990, rs915908, rs8192780, rs1536826, rs3827688 and one haplotype h2 (CGTGTTAA) were revealed to be significantly associated with the NPC phenotype (P = 0.045–0.003 and P = 0.003, respectively). To follow up the initial study, a case–control study including 755 cases and 755 controls was conducted. Similar results were observed in the case–control study in individuals <46 years of age and had a history of cigarette smoking, with odds ratios (ORs) of specific genotypes ranging from 1.88 to 2.99 corresponding to SNP rs9418990, rs3813865, rs915906, rs2249695, rs8192780, rs1536826, rs3827688 and of haplotypes h2 with OR = 1.65 (P = 0.026), h5 (CCCGTTAA) with OR = 2.58 (P = 0.007). The values of false-positive report probability were <0.015 for six SNPs, suggesting that the reported associations are less probably to be false. This study provides robust evidence for associations between genetic variants of CYP2E1 and NPC risk. PMID:19805575

  14. A Case-Control Study and Meta-Analysis Reveal BDNF Val66Met Is a Possible Risk Factor for PTSD

    Directory of Open Access Journals (Sweden)

    Dagmar Bruenig

    2016-01-01

    Full Text Available Posttraumatic stress disorder (PTSD is a debilitating condition that develops in some people after exposure to a traumatic event. Brain-derived neurotrophic factor (BDNF is highly expressed in the mammalian brain and is thought to be involved in learning and memory processes. A nonsynonymous polymorphism in the BDNF gene, rs6265 (Val66Met, has been hypothesised to be associated with PTSD. Association studies examining the Val66Met polymorphism and PTSD have been inconclusive, likely due to the variability in type of trauma exposure analysed. Vietnam veterans (n=257 screened for PTSD and controlled for trauma exposure were genotyped for BDNF Val66Met. The association was not significant so we incorporated our data into a meta-analysis to obtain greater statistical power. A comprehensive search of more than 1237 articles revealed eight additional studies suitable for meta-analysis (n=3625. A random-effects meta-analysis observed a potential protective factor of the Val/Val genotype. After removing two studies with violation of Hardy-Weinberg equilibrium, findings for the Val/Val genotype reached significance. Subgroup analyses confirmed a trend for this finding. Limitations of some studies that inform this meta-analysis include poorly screened controls and a lack of examination of population stratification. Effectively designed studies should inform this line of research in the future.

  15. Revealing Rembrandt

    Directory of Open Access Journals (Sweden)

    Andrew J Parker

    2014-04-01

    Full Text Available The power and significance of artwork in shaping human cognition is self-evident. The starting point for our empirical investigations is the view that the task of neuroscience is to integrate itself with other forms of knowledge, rather than to seek to supplant them. In our recent work, we examined a particular aspect of the appreciation of artwork using present-day functional magnetic resonance imaging (fMRI. Our results emphasised the continuity between viewing artwork and other human cognitive activities. We also showed that appreciation of a particular aspect of artwork, namely authenticity, depends upon the co-ordinated activity between the brain regions involved in multiple decision making and those responsible for processing visual information. The findings about brain function probably have no specific consequences for understanding how people respond to the art of Rembrandt in comparison with their response to other artworks. However, the use of images of Rembrandt’s portraits, his most intimate and personal works, clearly had a significant impact upon our viewers, even though they have been spatially confined to the interior of an MRI scanner at the time of viewing. Neuroscientific studies of humans viewing artwork have the capacity to reveal the diversity of human cognitive responses that may be induced by external advice or context as people view artwork in a variety of frameworks and settings.

  16. CREST Revealed

    DEFF Research Database (Denmark)

    Rapp, Hermann; Parisi, Cristiana; Bridgeman, Alfia

    This report covers the period from 1993 when the CREST project was initiated, to its launch in 1996, and considers the environment that prompted its instigation. The report looks at the massive cooperation of Government, industry and a range of different service providers that all came together......, under the central control of the CREST project team. It proposes five reasons why the CREST project was successful and examines why the CREST system continues to be at the heart of UK settlement, 20 years on....

  17. Linkage mapping in the oilseed crop Jatropha curcas L. reveals a locus controlling the biosynthesis of phorbol esters which cause seed toxicity.

    Science.gov (United States)

    King, Andrew J; Montes, Luis R; Clarke, Jasper G; Affleck, Julie; Li, Yi; Witsenboer, Hanneke; van der Vossen, Edwin; van der Linde, Piet; Tripathi, Yogendra; Tavares, Evanilda; Shukla, Parul; Rajasekaran, Thirunavukkarasu; van Loo, Eibertus N; Graham, Ian A

    2013-10-01

    Current efforts to grow the tropical oilseed crop Jatropha curcas L. economically are hampered by the lack of cultivars and the presence of toxic phorbol esters (PE) within the seeds of most provenances. These PE restrict the conversion of seed cake into animal feed, although naturally occurring 'nontoxic' provenances exist which produce seed lacking PE. As an important step towards the development of genetically improved varieties of J. curcas, we constructed a linkage map from four F₂ mapping populations. The consensus linkage map contains 502 codominant markers, distributed over 11 linkage groups, with a mean marker density of 1.8 cM per unique locus. Analysis of the inheritance of PE biosynthesis indicated that this is a maternally controlled dominant monogenic trait. This maternal control is due to biosynthesis of the PE occurring only within maternal tissues. The trait segregated 3 : 1 within seeds collected from F₂ plants, and QTL analysis revealed that a locus on linkage group 8 was responsible for phorbol ester biosynthesis. By taking advantage of the draft genome assemblies of J. curcas and Ricinus communis (castor), a comparative mapping approach was used to develop additional markers to fine map this mutation within 2.3 cM. The linkage map provides a framework for the dissection of agronomic traits in J. curcas, and the development of improved varieties by marker-assisted breeding. The identification of the locus responsible for PE biosynthesis means that it is now possible to rapidly breed new nontoxic varieties. © 2013 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  18. Partitioning of the net CO2 exchange using an automated chamber system reveals plant phenology as key control of production and respiration fluxes in a boreal peatland.

    Science.gov (United States)

    Järveoja, Järvi; Nilsson, Mats B; Gažovič, Michal; Crill, Patrick M; Peichl, Matthias

    2018-04-30

    The net ecosystem CO 2 exchange (NEE) drives the carbon (C) sink-source strength of northern peatlands. Since NEE represents a balance between various production and respiration fluxes, accurate predictions of its response to global changes require an in depth understanding of these underlying processes. Currently, however, detailed information of the temporal dynamics as well as the separate biotic and abiotic controls of the NEE component fluxes is lacking in peatland ecosystems. In this study, we address this knowledge gap by using an automated chamber system established across natural and trenching-/vegetation removal plots to partition NEE into its production (i.e. gross and net primary production; GPP and NPP) and respiration (i.e. ecosystem, heterotrophic and autotrophic respiration; ER, Rh and Ra) fluxes in a boreal peatland in northern Sweden. Our results showed that daily NEE patterns were driven by GPP while variations in ER were governed by Ra rather than Rh. Moreover, we observed pronounced seasonal shifts in the Ra/Rh and above-/belowground NPP ratios throughout the main phenological phases. Generalized linear model analysis revealed that the greenness index derived from digital images (as a proxy for plant phenology) was the strongest control of NEE, GPP and NPP while explaining considerable fractions also in the variations of ER and Ra. In addition, our data exposed greater temperature sensitivity of NPP compared to Rh resulting in enhanced C sequestration with increasing temperature. Overall, our study suggests that the temporal patterns in NEE and its component fluxes are tightly coupled to vegetation dynamics in boreal peatlands and thus challenges previous studies that commonly identify abiotic factors as key drivers. These findings further emphasize the need for integrating detailed information on plant phenology into process-based models to improve predictions of global change impacts on the peatland C cycle. This article is protected by

  19. STAT2 Knockout Syrian Hamsters Support Enhanced Replication and Pathogenicity of Human Adenovirus, Revealing an Important Role of Type I Interferon Response in Viral Control.

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    Karoly Toth

    2015-08-01

    Full Text Available Human adenoviruses have been studied extensively in cell culture and have been a model for studies in molecular, cellular, and medical biology. However, much less is known about adenovirus replication and pathogenesis in vivo in a permissive host because of the lack of an adequate animal model. Presently, the most frequently used permissive immunocompetent animal model for human adenovirus infection is the Syrian hamster. Species C human adenoviruses replicate in these animals and cause pathology that is similar to that seen with humans. Here, we report findings with a new Syrian hamster strain in which the STAT2 gene was functionally knocked out by site-specific gene targeting. Adenovirus-infected STAT2 knockout hamsters demonstrated an accentuated pathology compared to the wild-type control animals, and the virus load in the organs of STAT2 knockout animals was 100- to 1000-fold higher than that in wild-type hamsters. Notably, the adaptive immune response to adenovirus is not adversely affected in STAT2 knockout hamsters, and surviving hamsters cleared the infection by 7 to 10 days post challenge. We show that the Type I interferon pathway is disrupted in these hamsters, revealing the critical role of interferon-stimulated genes in controlling adenovirus infection. This is the first study to report findings with a genetically modified Syrian hamster infected with a virus. Further, this is the first study to show that the Type I interferon pathway plays a role in inhibiting human adenovirus replication in a permissive animal model. Besides providing an insight into adenovirus infection in humans, our results are also interesting from the perspective of the animal model: STAT2 knockout Syrian hamster may also be an important animal model for studying other viral infections, including Ebola-, hanta-, and dengue viruses, where Type I interferon-mediated innate immunity prevents wild type hamsters from being effectively infected to be used as

  20. Profiling MHC II immunopeptidome of blood-stage malaria reveals that cDC1 control the functionality of parasite-specific CD4 T cells.

    Science.gov (United States)

    Draheim, Marion; Wlodarczyk, Myriam F; Crozat, Karine; Saliou, Jean-Michel; Alayi, Tchilabalo Dilezitoko; Tomavo, Stanislas; Hassan, Ali; Salvioni, Anna; Demarta-Gatsi, Claudia; Sidney, John; Sette, Alessandro; Dalod, Marc; Berry, Antoine; Silvie, Olivier; Blanchard, Nicolas

    2017-11-01

    In malaria, CD4 Th1 and T follicular helper (T FH ) cells are important for controlling parasite growth, but Th1 cells also contribute to immunopathology. Moreover, various regulatory CD4 T-cell subsets are critical to hamper pathology. Yet the antigen-presenting cells controlling Th functionality, as well as the antigens recognized by CD4 T cells, are largely unknown. Here, we characterize the MHC II immunopeptidome presented by DC during blood-stage malaria in mice. We establish the immunodominance hierarchy of 14 MHC II ligands derived from conserved parasite proteins. Immunodominance is shaped differently whether blood stage is preceded or not by liver stage, but the same ETRAMP-specific dominant response develops in both contexts. In naïve mice and at the onset of cerebral malaria, CD8α + dendritic cells (cDC1) are superior to other DC subsets for MHC II presentation of the ETRAMP epitope. Using in vivo depletion of cDC1, we show that cDC1 promote parasite-specific Th1 cells and inhibit the development of IL-10 + CD4 T cells. This work profiles the P. berghei blood-stage MHC II immunopeptidome, highlights the potency of cDC1 to present malaria antigens on MHC II, and reveals a major role for cDC1 in regulating malaria-specific CD4 T-cell responses. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  1. Light-Mediated Kinetic Control Reveals the Temporal Effect of the Raf/MEK/ERK Pathway in PC12 Cell Neurite Outgrowth

    Science.gov (United States)

    Zhang, Kai; Duan, Liting; Ong, Qunxiang; Lin, Ziliang; Varman, Pooja Mahendra; Sung, Kijung; Cui, Bianxiao

    2014-01-01

    It has been proposed that differential activation kinetics allows cells to use a common set of signaling pathways to specify distinct cellular outcomes. For example, nerve growth factor (NGF) and epidermal growth factor (EGF) induce different activation kinetics of the Raf/MEK/ERK signaling pathway and result in differentiation and proliferation, respectively. However, a direct and quantitative linkage between the temporal profile of Raf/MEK/ERK activation and the cellular outputs has not been established due to a lack of means to precisely perturb its signaling kinetics. Here, we construct a light-gated protein-protein interaction system to regulate the activation pattern of the Raf/MEK/ERK signaling pathway. Light-induced activation of the Raf/MEK/ERK cascade leads to significant neurite outgrowth in rat PC12 pheochromocytoma cell lines in the absence of growth factors. Compared with NGF stimulation, light stimulation induces longer but fewer neurites. Intermittent on/off illumination reveals that cells achieve maximum neurite outgrowth if the off-time duration per cycle is shorter than 45 min. Overall, light-mediated kinetic control enables precise dissection of the temporal dimension within the intracellular signal transduction network. PMID:24667437

  2. Genetic mosaic analysis reveals a major role for frizzled 4 and frizzled 8 in controlling ureteric growth in the developing kidney.

    Science.gov (United States)

    Ye, Xin; Wang, Yanshu; Rattner, Amir; Nathans, Jeremy

    2011-03-01

    The developing mammalian kidney is an attractive system in which to study the control of organ growth. Targeted mutations in the Wnt receptors frizzled (Fz) 4 and Fz8 lead to reduced ureteric bud growth and a reduction in kidney size, a phenotype previously reported for loss of Wnt11. In cell culture, Fz4 and Fz8 can mediate noncanonical signaling stimulated by Wnt11, but only Fz4 mediates Wnt11-stimulated canonical signaling. In genetically mosaic mouse ureteric buds, competition between phenotypically mutant Fz4(-/-) or Fz4(-/-);Fz8(-/-) cells and adjacent phenotypically wild-type Fz4(+/-) or Fz4(+/-);Fz8(-/-) cells results in under-representation of the mutant cells to an extent far greater than would be predicted from the size reduction of homogeneously mutant kidneys. This discrepancy presumably reflects the compensatory action of a network of growth regulatory systems that minimize developmental perturbations. The present work represents the first description of a kidney phenotype referable to one or more Wnt receptors and demonstrates a general strategy for revealing the contribution of an individual growth regulatory pathway when it is part of a larger homeostatic network.

  3. Genetic activation, inactivation and deletion reveal a limited and nuanced role for somatostatin-containing basal forebrain neurons in behavioral state control.

    Science.gov (United States)

    Anaclet, Christelle; De Luca, Roberto; Venner, Anne; Malyshevskaya, Olga; Lazarus, Michael; Arrigoni, Elda; Fuller, Patrick M

    2018-05-07

    Recent studies have identified an especially important role for basal forebrain GABAergic (BF VGAT ) neurons in the regulation of behavioral waking and fast cortical rhythms associated with cognition. However, BF VGAT neurons comprise several neurochemically and anatomically distinct sub-populations, including parvalbumin- and somatostatin-containing BF VGAT neurons (BF Parv and BF SOM ), and it was recently reported that optogenetic activation of BF SOM neurons increases the probability of a wakefulness to non-rapid-eye movement (NREM) sleep transition when stimulated during the animal's rest period. This finding was unexpected given that most BF SOM neurons are not NREM sleep active and that central administration of the synthetic SOM analog, octreotide, suppresses NREM sleep or increases REM sleep. Here we employed a combination of genetically-driven chemogenetic and optogenetic activation, chemogenetic inhibition and ablation approaches to further explore the in vivo role of BF SOM neurons in arousal control. Our findings indicate that acute activation or inhibition of BF SOM neurons is neither wakefulness- nor NREM sleep-promoting, is without significant effect on the EEG, and that chronic loss of these neurons is without effect on total 24h sleep amounts, although a small but significant increase in waking was observed in the lesioned mice during the early active period. Our in vitro cell recordings further reveal electrophysiological heterogeneity in BF SOM neurons, specifically suggesting at least two distinct sub-populations. Taken together our data support the more nuanced view that BF SOM are electrically heterogeneous and are not NREM sleep- or wake-promoting per se , but may exert, in particular during the early active period, a modest inhibitory influence on arousal circuitry. SIGNIFICANCE STATEMENT The cellular basal forebrain (BF) is a highly complex area of the brain that is implicated in a wide-range of higher-level neurobiological processes

  4. Tissue-specific inactivation of type 2 deiodinase reveals multilevel control of fatty acid oxidation by thyroid hormone in the mouse.

    Science.gov (United States)

    Fonseca, Tatiana L; Werneck-De-Castro, Joao Pedro; Castillo, Melany; Bocco, Barbara M L C; Fernandes, Gustavo W; McAninch, Elizabeth A; Ignacio, Daniele L; Moises, Caio C S; Ferreira, Alexander R; Ferreira, Alexandre; Gereben, Balázs; Bianco, Antonio C

    2014-05-01

    Type 2 deiodinase (D2) converts the prohormone thyroxine (T4) to the metabolically active molecule 3,5,3'-triiodothyronine (T3), but its global inactivation unexpectedly lowers the respiratory exchange rate (respiratory quotient [RQ]) and decreases food intake. Here we used FloxD2 mice to generate systemically euthyroid fat-specific (FAT), astrocyte-specific (ASTRO), or skeletal-muscle-specific (SKM) D2 knockout (D2KO) mice that were monitored continuously. The ASTRO-D2KO mice also exhibited lower diurnal RQ and greater contribution of fatty acid oxidation to energy expenditure, but no differences in food intake were observed. In contrast, the FAT-D2KO mouse exhibited sustained (24 h) increase in RQ values, increased food intake, tolerance to glucose, and sensitivity to insulin, all supporting greater contribution of carbohydrate oxidation to energy expenditure. Furthermore, FAT-D2KO animals that were kept on a high-fat diet for 8 weeks gained more body weight and fat, indicating impaired brown adipose tissue (BAT) thermogenesis and/or inability to oxidize the fat excess. Acclimatization of FAT-D2KO mice at thermoneutrality dissipated both features of this phenotype. Muscle D2 does not seem to play a significant metabolic role given that SKM-D2KO animals exhibited no phenotype. The present findings are unique in that they were obtained in systemically euthyroid animals, revealing that brain D2 plays a dominant albeit indirect role in fatty acid oxidation via its sympathetic control of BAT activity. D2-generated T3 in BAT accelerates fatty acid oxidation and protects against diet-induced obesity.

  5. The C. elegans DSB-2 protein reveals a regulatory network that controls competence for meiotic DSB formation and promotes crossover assurance.

    Directory of Open Access Journals (Sweden)

    Simona Rosu

    Full Text Available For most organisms, chromosome segregation during meiosis relies on deliberate induction of DNA double-strand breaks (DSBs and repair of a subset of these DSBs as inter-homolog crossovers (COs. However, timing and levels of DSB formation must be tightly controlled to avoid jeopardizing genome integrity. Here we identify the DSB-2 protein, which is required for efficient DSB formation during C. elegans meiosis but is dispensable for later steps of meiotic recombination. DSB-2 localizes to chromatin during the time of DSB formation, and its disappearance coincides with a decline in RAD-51 foci marking early recombination intermediates and precedes appearance of COSA-1 foci marking CO-designated sites. These and other data suggest that DSB-2 and its paralog DSB-1 promote competence for DSB formation. Further, immunofluorescence analyses of wild-type gonads and various meiotic mutants reveal that association of DSB-2 with chromatin is coordinated with multiple distinct aspects of the meiotic program, including the phosphorylation state of nuclear envelope protein SUN-1 and dependence on RAD-50 to load the RAD-51 recombinase at DSB sites. Moreover, association of DSB-2 with chromatin is prolonged in mutants impaired for either DSB formation or formation of downstream CO intermediates. These and other data suggest that association of DSB-2 with chromatin is an indicator of competence for DSB formation, and that cells respond to a deficit of CO-competent recombination intermediates by prolonging the DSB-competent state. In the context of this model, we propose that formation of sufficient CO-competent intermediates engages a negative feedback response that leads to cessation of DSB formation as part of a major coordinated transition in meiotic prophase progression. The proposed negative feedback regulation of DSB formation simultaneously (1 ensures that sufficient DSBs are made to guarantee CO formation and (2 prevents excessive DSB levels that could

  6. Loss of genetic variability in a hatchery strain of Senegalese sole (Solea senegalensis revealed by sequence data of the mitochondrial DNA control region and microsatellite markers

    Directory of Open Access Journals (Sweden)

    Pablo Sánchez

    2012-06-01

    Full Text Available Comparisons of the levels of genetic variation within and between a hatchery F1 (FAR, n=116 of Senegalese sole, Solea senegalensis, and its wild donor population (ATL, n = 26, both native to the SW Atlantic coast of the Iberian peninsula, as well as between the wild donor population and a wild western Mediterranean sample (MED, n=18, were carried out by characterizing 412 base pairs of the nucleotide sequence of the mitochondrial DNA control region I, and six polymorphic microsatellite loci. FAR showed a substantial loss of genetic variability (haplotypic diversity, h=0.49±0.066; nucleotide diversity, π=0.006±0.004; private allelic richness, pAg=0.28 to its donor population ATL (h=0.69±0.114; π=0.009±0.006; pAg=1.21. Pairwise FST values of microsatellite data were highly significant (P < 0.0001 between FAR and ATL (0.053 and FAR and MED (0.055. The comparison of wild samples revealed higher values of genetic variability in MED than in ATL, but only with mtDNA CR-I sequence data (h=0.948±0.033; π=0.030±0.016. However, pairwise ΦST and FST values between ATL and MED were highly significant (P < 0.0001 with mtDNA CR-I (0.228 and with microsatellite data (0.095, respectively. While loss of genetic variability in FAR could be associated with the sampling error when the broodstock was established, the results of parental and sibship inference suggest that most of these losses can be attributed to a high variance in reproductive success among members of the broodstock, particularly among females.

  7. Applying machine learning to global surface ocean and seabed data to reveal the controls on the distribution of deep-sea sediments

    Science.gov (United States)

    Dutkiewicz, Adriana; Müller, Dietmar; O'Callaghan, Simon

    2017-04-01

    World's ocean basins contain a rich and nearly continuous record of environmental fluctuations preserved as different types of deep-sea sediments. The sediments represent the largest carbon sink on Earth and its largest geological deposit. Knowing the controls on the distribution of these sediments is essential for understanding the history of ocean-climate dynamics, including changes in sea-level and ocean circulation, as well as biological perturbations. Indeed, the bulk of deep-sea sediments comprises the remains of planktonic organisms that originate in the photic zone of the global ocean implying a strong connection between the seafloor and the sea surface. Machine-learning techniques are perfectly suited to unravelling these controls as they are able to handle large sets of spatial data and they often outperform traditional spatial analysis approaches. Using a support vector machine algorithm we recently created the first digital map of seafloor lithologies (Dutkiewicz et al., 2015) based on 14,400 surface samples. This map reveals significant deviations in distribution of deep-sea lithologies from hitherto hand-drawn maps based on far fewer data points. It also allows us to explore quantitatively, for the first time, the relationship between oceanographic parameters at the sea surface and lithologies on the seafloor. We subsequently coupled this global point sample dataset of 14,400 seafloor lithologies to bathymetry and oceanographic grids (sea-surface temperature, salinity, dissolved oxygen and dissolved inorganic nutrients) and applied a probabilistic Gaussian process classifier in an exhaustive combinatorial fashion (Dutkiewicz et al., 2016). We focused on five major lithologies (calcareous sediment, diatom ooze, radiolarian ooze, clay and lithogenous sediment) and used a computationally intensive five-fold cross-validation, withholding 20% of the data at each iteration, to assess the predictive performance of the machine learning method. We find that

  8. Toxic death of mouse small intestinal enterocytes as a function of intervals between injections of the S-phase-specific agent hydroxyurea

    International Nuclear Information System (INIS)

    Churikova, L.I.; Krinskaya, A.V.; Dibrov, B.F.; Zhabotinskii, A.M.; Neifakh, Yu.A.; Gel'fand, E.V.

    1986-01-01

    The authors study optimal conditions for administration of hydroxyurea to mice to ensure minimal damage to intestinal enterocytes. Before receiving an injection of hydroxyurea the mice were irradiated in a dose of 200 rads from a 137 Cs source to activate proliferation of the epithelial cells. The morphometric parameters of the epithelium after injection of hydroxyurea are given. A resonance increase in the survival rate of the enterocytes was revealed if the cytostatic was injected with a period close to the average duration of the cell cycle of the regenerating intestinal cells

  9. The influence of cycling temperature and cycling rate on the phase specific degradation of a positive electrode in lithium ion batteries: A post mortem analysis

    Science.gov (United States)

    Darma, Mariyam Susana Dewi; Lang, Michael; Kleiner, Karin; Mereacre, Liuda; Liebau, Verena; Fauth, Francois; Bergfeldt, Thomas; Ehrenberg, Helmut

    2016-09-01

    The influence of cycling temperatures and cycling rates on the cycling stability of the positive electrode (cathode) of commercial batteries are investigated. The cathode is a mixture of LiMn2O4 (LMO), LiNi0.5Co0.2Mn0.3O2 (NCM) and LiNi0.8Co0.15Al0.05O2 (NCA). It is found that increasing the cycling temperature from 25 °C to 40 °C is detrimental to the long term cycling stability of the cathode. Contrastingly, the improved cycling stability is observed for the cathodes cycled at higher charge/discharge rate (2C/3C instead of 1C/2C). The microstructure analysis by X-ray powder diffraction reveals that a significant capacity fading and an increased overvoltage is observed for NCM and NCA in all the fatigued cathodes. After high number of cycling (above 1500 cycles), NCM becomes partially inactive. In contrast to NCM and NCA, LMO shows a good cycling stability at 25 °C. A pronounced degradation of LMO is only observed for the fatigued cathodes cycled at 40 °C. The huge capacity losses of NCM and NCA are most likely because the blended cathodes were cycled up to 4.12 V vs. the graphite anode during the cycle-life test (corresponds to 4.16 V vs. Li+/Li); which is beyond the stability limit of the layered oxides below 4.05 V vs. Li+/Li.

  10. Antiviral activity of Small interfering RNAs: Specificity testing using heterologous virus reveals interferon-related effects overlooked by conventional mismatch controls

    DEFF Research Database (Denmark)

    Schyth, Brian Dall; Lorenzen, Niels; Pedersen, Finn Skou

    2006-01-01

    to the viral glycoprotein gene of the target-virus efficiently inhibited viral multiplication in infected cell cultures, while two of three corresponding mismatched siRNAs did not have this effect. This suggested specific interference, but similar results were obtained when the same siRNAs were tested against...... a heterologous virus. Further analyses revealed that the siRNAs induced a non-target-specific anti-viral effect correlating with upregulation of the interferon induced Mx gene....

  11. S-phase Specific Downregulation of Human O6-Methylguanine DNA Methyltransferase (MGMT and its Serendipitous Interactions with PCNA and p21cip1 Proteins in Glioma Cells

    Directory of Open Access Journals (Sweden)

    AGM Mostofa

    2018-04-01

    Full Text Available Whether the antimutagenic DNA repair protein MGMT works solo in human cells and if it has other cellular functions is not known. Here, we show that human MGMT associates with PCNA and in turn, with the cell cycle inhibitor, p21cip1 in glioblastoma and other cancer cell lines. MGMT protein was shown to harbor a nearly perfect PCNA-Interacting Protein (PIP box motif. Isogenic p53-null H1299 cells were engineered to express the p21 protein by two different procedures. Reciprocal immunoprecipitation/western blotting, Far-western blotting, and confocal microscopy confirmed the specific association of MGMT with PCNA and the ability of p21 to strongly disrupt the MGMT-PCNA complexes in tumor cells. Alkylation DNA damage resulted in a greater colocalization of MGMT and PCNA proteins, particularly in HCT116 cells deficient in p21 expression. p21 expression in isogenic cell lines directly correlated with markedly higher levels of MGMT mRNA, protein, activity and greater resistance to alkylating agents. In other experiments, four glioblastoma cell lines synchronized at the G1/S phase using either double thymidine or thymidine-mimosine blocks and subsequent cycling consistently showed a loss of MGMT protein at mid- to late S-phase, irrespective of the cell line, suggesting such a downregulation is fundamental to cell cycle control. MGMT protein was also specifically degraded in extracts from S-phase cells and evidence strongly suggested the involvement of PCNA-dependent CRL4Cdt2 ubiquitin-ligase in the reaction. Overall, these data provide the first evidence for non-repair functions of MGMT in cell cycle and highlight the involvement of PCNA in MGMT downregulation, with p21 attenuating the process.

  12. Lymphogranuloma venereum diagnoses among men who have sex with men in the U.K.: interpreting a cross-sectional study using an epidemic phase-specific framework.

    Science.gov (United States)

    Hughes, Gwenda; Alexander, Sarah; Simms, Ian; Conti, Stefano; Ward, Helen; Powers, Cassandra; Ison, Catherine

    2013-11-01

    To investigate the drivers behind the epidemic expansion of lymphogranuloma venereum (LGV) cases in late 2009 to help inform infection control. An epidemic curve of all LGV diagnoses between 2003 and mid-2012 was plotted and divided into the initial detection period, and endemic, growth and hyperendemic phases. Detailed clinical and behavioural data were collected and logistic regression was used to compare the characteristics of diagnoses made during the growth and endemic phases. Between April 2003 and June 2012, 2138 cases of LGV were diagnosed. Enhanced surveillance data were available for 1370 of whom 1353 were men who have sex with men (MSM). 98% of MSM presented with proctitis, 82% were HIV positive, 20% were hepatitis C virus (HCV) antibody positive, and 67% lived in London. Growth phase cases (n=488) were more likely to report meeting sexual contacts at sex parties (11% vs. 6%, p=0.014), unprotected receptive or insertive oral intercourse (93% vs. 86%, p=0.001; 92% vs. 85%, p=0.001) and sharing sex toys (8% vs 4%; p=0.011), and to be diagnosed HIV positive (86% vs. 80%; p=0.014), than endemic phase cases (n=423). Unprotected receptive anal intercourse was equally likely to be reported in both phases (71% vs. 73%). After adjustment, cases in the growth phase were more likely to meet new contacts at sex parties (p=0.031) and be HIV positive (p=0.045). Rapid epidemic growth coincided with an intensification of unprotected sexual activity among a core population of HIV-positive MSM. Efforts to develop innovative interventions for this hard-to-reach population are needed.

  13. Mutations in fam20b and xylt1 reveal that cartilage matrix controls timing of endochondral ossification by inhibiting chondrocyte maturation.

    Directory of Open Access Journals (Sweden)

    B Frank Eames

    2011-08-01

    Full Text Available Differentiating cells interact with their extracellular environment over time. Chondrocytes embed themselves in a proteoglycan (PG-rich matrix, then undergo a developmental transition, termed "maturation," when they express ihh to induce bone in the overlying tissue, the perichondrium. Here, we ask whether PGs regulate interactions between chondrocytes and perichondrium, using zebrafish mutants to reveal that cartilage PGs inhibit chondrocyte maturation, which ultimately dictates the timing of perichondral bone development. In a mutagenesis screen, we isolated a class of mutants with decreased cartilage matrix and increased perichondral bone. Positional cloning identified lesions in two genes, fam20b and xylosyltransferase1 (xylt1, both of which encode PG synthesis enzymes. Mutants failed to produce wild-type levels of chondroitin sulfate PGs, which are normally abundant in cartilage matrix, and initiated perichondral bone formation earlier than their wild-type siblings. Primary chondrocyte defects might induce the bone phenotype secondarily, because mutant chondrocytes precociously initiated maturation, showing increased and early expression of such markers as runx2b, collagen type 10a1, and ihh co-orthologs, and ihha mutation suppressed early perichondral bone in PG mutants. Ultrastructural analyses demonstrated aberrant matrix organization and also early cellular features of chondrocyte hypertrophy in mutants. Refining previous in vitro reports, which demonstrated that fam20b and xylt1 were involved in PG synthesis, our in vivo analyses reveal that these genes function in cartilage matrix production and ultimately regulate the timing of skeletal development.

  14. Combating a Global Threat to a Clonal Crop: Banana Black Sigatoka Pathogen Pseudocercospora fijiensis (Synonym Mycosphaerella fijiensis) Genomes Reveal Clues for Disease Control

    NARCIS (Netherlands)

    Arango Isaza, Rafael E.; Diaz-Trujillo, Caucasella; Dhillon, Braham; Aerts, Andrea; Carlier, Jean; Crane, Charles F.; V. de Jong, Tristan; de Vries, Ineke; Dietrich, Robert; Farmer, Andrew D.; Fortes Fereira, Claudia; Garcia, Suzana; Guzman, Mauricio; Hamelin, Richard C.; Lindquist, Erika A.; Mehrabi, Rahim; Quiros, Olman; Schmutz, Jeremy; Shapiro, Harris; Reynolds, Elizabeth; Scalliet, Gabriel; Souza Manoel, Jr.; Stergiopoulos, Ioannis; Van der Lee, Theo A. J.; De Wit, Pierre J. G. M.; Zapater, Marie-Françoise; Zwiers, Lute-Harm; Grigoriev, Igor V.; Goodwin, Stephen B.; Kema, Gert H. J.

    2016-01-01

    Black Sigatoka or black leaf streak disease, caused by the ascomycete fungus Pseudocercospora fijiensis, inflicts huge costs on banana producers, due to crop losses and expenses for disease control. The global banana export trade relies on Cavendish clones that are highly susceptible to P.

  15. Molecular gut-content analysis of a predator assemblage reveals the effect of habitat manipulation on biological control in the field

    Science.gov (United States)

    Despite growing evidence that habitat manipulation can alter predators’ impact on target prey consumption, few studies have directly examined the effect of habitat context on conservation biological control in the field. Because of contradictory evidence in the literature for the outcome of habita...

  16. Combating a global threat to a clonal crop: banana black sigatoka pathogen pseudocercospora fijiensis (synonym mycosphaerella fijiensis) genomes reveal clues for disease control

    Science.gov (United States)

    Mycosphaerella fijiensis is the fungal pathogen that causes black Sigatoka or leaf streak disease of banana. Control of this disease requires weekly applications of fungicides in most cultivation areas. Major problems for disease management are fungicide resistance and the lack of effective genes fo...

  17. Health access livelihood framework reveals potential barriers in the control of schistosomiasis in the Dongting Lake area of Hunan Province, China.

    Directory of Open Access Journals (Sweden)

    Julie Balen

    Full Text Available Access to health care is a major requirement in improving health and fostering socioeconomic development. In the People's Republic of China (P.R. China, considerable changes have occurred in the social, economic, and health systems with a shift from a centrally planned to a socialist market economy. This brought about great benefits and new challenges, particularly for vertical disease control programs, including schistosomiasis. We explored systemic barriers in access to equitable and effective control of schistosomiasis.Between August 2002 and February 2003, 66 interviews with staff from anti-schistosomiasis control stations and six focus group discussions with health personnel were conducted in the Dongting Lake area, Hunan Province. Additionally, 79 patients with advanced schistosomiasis japonica were interviewed. The health access livelihood framework was utilized to examine availability, accessibility, affordability, adequacy, and acceptability of schistosomiasis-related health care.We found sufficient availability of infrastructure and human resources at most control stations. Many patients with advanced schistosomiasis resided in non-endemic or moderately endemic areas, however, with poor accessibility to disease-specific knowledge and specialized health services. Moreover, none of the patients interviewed had any form of health insurance, resulting in high out-of-pocket expenditure or unaffordable care. Reports on the adequacy and acceptability of care were mixed.There is a need to strengthen health awareness and schistosomiasis surveillance in post-transmission control settings, as well as to reduce diagnostic and treatment costs. Further studies are needed to gain a multi-layered, in-depth understanding of remaining barriers, so that the ultimate goal of schistosomiasis elimination in P.R. China can be reached.

  18. Metabolomic Profiling of Post-Mortem Brain Reveals Changes in Amino Acid and Glucose Metabolism in Mental Illness Compared with Controls

    Directory of Open Access Journals (Sweden)

    Rong Zhang

    2016-01-01

    Full Text Available Metabolomic profiling was carried out on 53 post-mortem brain samples from subjects diagnosed with schizophrenia, depression, bipolar disorder (SDB, diabetes, and controls. Chromatography on a ZICpHILIC column was used with detection by Orbitrap mass spectrometry. Data extraction was carried out with m/z Mine 2.14 with metabolite searching against an in-house database. There was no clear discrimination between the controls and the SDB samples on the basis of a principal components analysis (PCA model of 755 identified or putatively identified metabolites. Orthogonal partial least square discriminant analysis (OPLSDA produced clear separation between 17 of the controls and 19 of the SDB samples (R2CUM 0.976, Q2 0.671, p-value of the cross-validated ANOVA score 0.0024. The most important metabolites producing discrimination were the lipophilic amino acids leucine/isoleucine, proline, methionine, phenylalanine, and tyrosine; the neurotransmitters GABA and NAAG and sugar metabolites sorbitol, gluconic acid, xylitol, ribitol, arabinotol, and erythritol. Eight samples from diabetic brains were analysed, six of which grouped with the SDB samples without compromising the model (R2 CUM 0.850, Q2 CUM 0.534, p-value for cross-validated ANOVA score 0.00087. There appears on the basis of this small sample set to be some commonality between metabolic perturbations resulting from diabetes and from SDB.

  19. Circadian profiling reveals higher histamine plasma levels and lower diamine oxidase serum activities in 24% of patients with suspected histamine intolerance compared to food allergy and controls.

    Science.gov (United States)

    Pinzer, T C; Tietz, E; Waldmann, E; Schink, M; Neurath, M F; Zopf, Y

    2018-04-01

    Histamine intolerance is thought to trigger manifold clinical symptoms after ingesting histamine-rich food due to reduced activity of diamine oxidase (DAO). No study has hitherto systematically assessed daily fluctuations of histamine levels and DAO activities in symptomatic patients. The aim of the study was to investigate the presence of histamine intolerance, to therefore establish day profiles of histamine levels and DAO activities, and to compare the results between patients with suspected histamine intolerance, food allergy and healthy controls. We determined day profiles of histamine plasma levels and DAO serum activities in 33 patients with suspected histamine intolerance, in 21 patients with proven food allergy and in 10 healthy control patients. Clinical symptoms, food intolerances and further clinical and laboratory chemical parameters were evaluated. Twenty-four percent (8 of 33) suspected histamine-intolerant patients showed elevated histamine levels during the day. That might be caused by constantly and significantly reduced DAO activities in these patients compared to food-allergic and control patients. The remaining 25 patients presented normal histamine levels and DAO activities, but an increased prevalence of multiple food intolerances compared to the other subgroup of suspected histamine-intolerants. There was no correlation between subjective complaints and serological histamine parameters in patients with suspected histamine intolerance. We determined by daily profiling that decreased DAO activities correlated with elevated histamine levels in a subgroup of suspected histamine-intolerants. This finding discriminates these patients from food intolerant individuals with similar clinical symptoms and strongly suggests the presence of histamine intolerance. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  20. A large case-control study reveals a positive association between bisphosphonate use and delayed dental healing and osteonecrosis of the jaw.

    Science.gov (United States)

    Borromeo, Gelsomina L; Brand, Caroline; Clement, John G; McCullough, Michael; Crighton, Lisa; Hepworth, Graham; Wark, John D

    2014-06-01

    This study sought to investigate, using a case-control study design, the association between bisphosphonate therapy and delayed dental healing and osteonecrosis of the jaw. Identification of potential cases of delayed dental healing was by consecutive screening of Specialist Oral and Maxillofacial and Special Needs Dentist clinic records for patients aged older than 50 years, during a 6-month window, in Victoria, Australia. Cases were confirmed by a case adjudication panel blinded to bisphosphonate status. Cases associated with malignancy or local radiotherapy were excluded. Controls were matched for age, sex, and source of dental referral (1:4, n = 160 controls). Variables of interest were dental precipitants, dental clinic type, smoking history, and medical comorbidities. A total of 4212 of 22,358 patients met inclusion criteria, of which 69 were potential cases with 40 (0.95%) confirmed cases. The odds ratio (OR) for developing delayed dental healing when taking an oral bisphosphonate was 13.1 (95% confidence interval [CI] 4.4 to 39.3; p associated with intravenous bisphosphonate use. There was some evidence of an interaction with age, sex, and clinic type. When adjusted for smoking, the estimated odds ratio was 11.6 (95% CI 1.9 to 69.4; p = 0.01). There was an association between having another illness and delayed dental healing (OR = 2.3; 95% CI 1.0 to 5.2). A dental precipitant was present in 39 of 40 (97.5%) delayed dental healing cases. An important association between bisphosphonate use and delayed dental healing in the setting of benign bone disease, predominately in individuals with a dental precipitant, has been demonstrated. © 2014 American Society for Bone and Mineral Research.

  1. The ventralizing activity of Radar, a maternally expressed bone morphogenetic protein, reveals complex bone morphogenetic protein interactions controlling dorso-ventral patterning in zebrafish.

    Science.gov (United States)

    Goutel, C; Kishimoto, Y; Schulte-Merker, S; Rosa, F

    2000-12-01

    In Xenopus and zebrafish, BMP2, 4 and 7 have been implicated, after the onset of zygotic expression, in inducing and maintaining ventro-lateral cell fate during early development. We provide evidence here that a maternally expressed bone morphogenetic protein (BMP), Radar, may control early ventral specification in zebrafish. We show that Radar ventralizes zebrafish embryos and induces the early expression of bmp2b and bmp4. The analysis of Radar overexpression in both swirl/bmp2b mutants and embryos expressing truncated BMP receptors shows that Radar-induced ventralization is dependent on functional BMP2/4 pathways, and may initially rely on an Alk6-related signaling pathway. Finally, we show that while radar-injected swirl embryos still exhibit a strongly dorsalized phenotype, the overexpression of Radar into swirl/bmp2b mutant embryos restores ventral marker expression, including bmp4 expression. Our results suggest that a complex regulation of different BMP pathways controls dorso-ventral (DV) patterning from early cleavage stages until somitogenesis.

  2. Association of environmental markers with childhood type 1 diabetes mellitus revealed by a long questionnaire on early life exposures and lifestyle in a case–control study

    Directory of Open Access Journals (Sweden)

    F. Balazard

    2016-09-01

    Full Text Available Abstract Background The incidence of childhood type 1 diabetes (T1D incidence is rising in many countries, supposedly because of changing environmental factors, which are yet largely unknown. The purpose of the study was to unravel environmental markers associated with T1D. Methods Cases were children with T1D from the French Isis-Diab cohort. Controls were schoolmates or friends of the patients. Parents were asked to fill a 845-item questionnaire investigating the child’s environment before diagnosis. The analysis took into account the matching between cases and controls. A second analysis used propensity score methods. Results We found a negative association of several lifestyle variables, gastroenteritis episodes, dental hygiene, hazelnut cocoa spread consumption, wasp and bee stings with T1D, consumption of vegetables from a farm and death of a pet by old age. Conclusions The found statistical association of new environmental markers with T1D calls for replication in other cohorts and investigation of new environmental areas. Trial registration Clinical-Trial.gov NCT02212522 . Registered August 6, 2014. 

  3. Characterizing and controlling intrinsic biases of lambda exonuclease in nascent strand sequencing reveals phasing between nucleosomes and G-quadruplex motifs around a subset of human replication origins

    DEFF Research Database (Denmark)

    Foulk, M. S.; Urban, J. M.; Casella, Cinzia

    2015-01-01

    Nascent strand sequencing (NS-seq) is used to discover DNA replication origins genome-wide, allowing identification of features for their specification. NS-seq depends on the ability of lambda exonuclease (lambda-exo) to efficiently digest parental DNA while leaving RNA-primer protected nascent...... strands intact. We used genomics and biochemical approaches to determine if lambda-exo digests all parental DNA sequences equally. We report that lambda-exo does not efficiently digest G-quadruplex (G4) structures in a plasmid. Moreover, lambda-exo digestion of nonreplicating genomic DNA (LexoG0) enriches...... GC-rich DNA and G4 motifs genome-wide. We used LexoG0 data to control for nascent strand-independent lambda-exo biases in NSseq and validated this approach at the rDNA locus. The lambda-exo-controlled NS-seq peaks are not GC-rich, and only 35.5% overlap with 6.8% of all G4s, suggesting that G4s...

  4. Genome-wide QTL and bulked transcriptomic analysis reveals new candidate genes for the control of tuber carotenoid content in potato (Solanum tuberosum L.).

    Science.gov (United States)

    Campbell, Raymond; Pont, Simon D A; Morris, Jenny A; McKenzie, Gaynor; Sharma, Sanjeev Kumar; Hedley, Pete E; Ramsay, Gavin; Bryan, Glenn J; Taylor, Mark A

    2014-09-01

    Genome-wide QTL analysis of potato tuber carotenoid content was investigated in populations of Solanum tuberosum Group Phureja that segregate for flesh colour, revealing a novel major QTL on chromosome 9. The carotenoid content of edible plant storage organs is a key nutritional and quality trait. Although the structural genes that encode the biosynthetic enzymes are well characterised, much less is known about the factors that determine overall storage organ content. In this study, genome-wide QTL mapping, in concert with an efficient 'genetical genomics' analysis using bulked samples, has been employed to investigate the genetic architecture of potato tuber carotenoid content. Two diploid populations of Solanum tuberosum Group Phureja were genotyped (AFLP, SSR and DArT markers) and analysed for their tuber carotenoid content over two growing seasons. Common to both populations were QTL that explained relatively small proportions of the variation in constituent carotenoids and a major QTL on chromosome 3 explaining up to 71 % of the variation in carotenoid content. In one of the populations (01H15), a second major carotenoid QTL was identified on chromosome 9, explaining up to 20 % of the phenotypic variation. Whereas the major chromosome 3 QTL was likely to be due to an allele of a gene encoding β-carotene hydroxylase, no known carotenoid biosynthetic genes are located in the vicinity of the chromosome 9 QTL. A unique expression profiling strategy using phenotypically distinct bulks comprised individuals with similar carotenoid content provided further support for the QTL mapping to chromosome 9. This study shows the potential of using the potato genome sequence to link genetic maps to data arising from eQTL approaches to enhance the discovery of candidate genes underlying QTLs.

  5. Control over the Strength of Connections Between Modules: A Double Dissociation Between Stimulus Format and Task Revealed by Granger Causality Mapping in fMRI

    Directory of Open Access Journals (Sweden)

    Britt eAnderson

    2015-03-01

    Full Text Available Drawing on theoretical and computational work with the localist Dual Route reading model and results from behavioral studies, Besner, Moroz, and O'Malley (2011 proposed that the ability to perform tasks that require overriding stimulus-specific defaults (e.g., semantics when naming Arabic numerals, and phonology when evaluating the parity of number words necessitate the ability to modulate the strength of connections between cognitive modules for lexical representation, semantics, and phonology on a task- and stimulus-specific basis. We used fMRI to evaluate this account by assessing changes in functional connectivity while participants performed tasks that did and did not require such stimulus-task default overrides. The occipital region showing the greatest modulation of BOLD signal strength for the two stimulus types was used as the seed region for Granger Causality Mapping (GCM. Our GCM analysis revealed a region of rostromedial frontal cortex with a crossover interaction. When participants performed tasks that required overriding stimulus type defaults (i.e., parity judgments of number words and naming Arabic numerals functional connectivity between the occipital region and rostromedial frontal cortex was present. Statistically significant functional connectivity was absent when the tasks were the default for the stimulus type (i.e., parity judgments of Arabic numerals and reading number words. This frontal region (BA 10 has previously been shown to be involved in goal-directed behaviour and maintenance of a specific task-set. We conclude that overriding stimulus-task defaults requires a modulation of connection strengths between cognitive modules and that the override mechanism predicted from cognitive theory is instantiated by frontal modulation of neural activity of brain regions specialized for sensory processing.

  6. Discovering human germ cell mutagens with whole genome sequencing: Insights from power calculations reveal the importance of controlling for between-family variability.

    Science.gov (United States)

    Webster, R J; Williams, A; Marchetti, F; Yauk, C L

    2018-07-01

    Mutations in germ cells pose potential genetic risks to offspring. However, de novo mutations are rare events that are spread across the genome and are difficult to detect. Thus, studies in this area have generally been under-powered, and no human germ cell mutagen has been identified. Whole Genome Sequencing (WGS) of human pedigrees has been proposed as an approach to overcome these technical and statistical challenges. WGS enables analysis of a much wider breadth of the genome than traditional approaches. Here, we performed power analyses to determine the feasibility of using WGS in human families to identify germ cell mutagens. Different statistical models were compared in the power analyses (ANOVA and multiple regression for one-child families, and mixed effect model sampling between two to four siblings per family). Assumptions were made based on parameters from the existing literature, such as the mutation-by-paternal age effect. We explored two scenarios: a constant effect due to an exposure that occurred in the past, and an accumulating effect where the exposure is continuing. Our analysis revealed the importance of modeling inter-family variability of the mutation-by-paternal age effect. Statistical power was improved by models accounting for the family-to-family variability. Our power analyses suggest that sufficient statistical power can be attained with 4-28 four-sibling families per treatment group, when the increase in mutations ranges from 40 to 10% respectively. Modeling family variability using mixed effect models provided a reduction in sample size compared to a multiple regression approach. Much larger sample sizes were required to detect an interaction effect between environmental exposures and paternal age. These findings inform study design and statistical modeling approaches to improve power and reduce sequencing costs for future studies in this area. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  7. Gene expression profiling in the stress control brain region hypothalamic paraventricular nucleus reveals a novel gene network including Amyloid beta Precursor Protein

    Directory of Open Access Journals (Sweden)

    Deussing Jan M

    2010-10-01

    Full Text Available Abstract Background The pivotal role of stress in the precipitation of psychiatric diseases such as depression is generally accepted. This study aims at the identification of genes that are directly or indirectly responding to stress. Inbred mouse strains that had been evidenced to differ in their stress response as well as in their response to antidepressant treatment were chosen for RNA profiling after stress exposure. Gene expression and regulation was determined by microarray analyses and further evaluated by bioinformatics tools including pathway and cluster analyses. Results Forced swimming as acute stressor was applied to C57BL/6J and DBA/2J mice and resulted in sets of regulated genes in the paraventricular nucleus of the hypothalamus (PVN, 4 h or 8 h after stress. Although the expression changes between the mouse strains were quite different, they unfolded in phases over time in both strains. Our search for connections between the regulated genes resulted in potential novel signalling pathways in stress. In particular, Guanine nucleotide binding protein, alpha inhibiting 2 (GNAi2 and Amyloid β (A4 precursor protein (APP were detected as stress-regulated genes, and together with other genes, seem to be integrated into stress-responsive pathways and gene networks in the PVN. Conclusions This search for stress-regulated genes in the PVN revealed its impact on interesting genes (GNAi2 and APP and a novel gene network. In particular the expression of APP in the PVN that is governing stress hormone balance, is of great interest. The reported neuroprotective role of this molecule in the CNS supports the idea that a short acute stress can elicit positive adaptational effects in the brain.

  8. A socioeconomic and behavioral survey of patients with difficult-to-control type 2 diabetes mellitus reveals an association between diabetic retinopathy and educational attainment

    Directory of Open Access Journals (Sweden)

    Emoto N

    2016-10-01

    Full Text Available Naoya Emoto,1,2 Fumitaka Okajima,1,2 Hitoshi Sugihara,2 Rei Goto3 1Department of Endocrinology, Nippon Medical School Chiba-Hokusoh Hospital, Chiba, 2Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, 3Graduate School of Business Administration, Keio University, Kanagawa, Japan Background: We have recently reported that the attitude of patients toward risk could be a factor in the progression of diabetic complications. In general, risk preference is closely related to socioeconomic status (SES, which includes factors such as age, sex, income, and educational attainment.Objective: We aimed to determine the effect of SES and behavioral propensity on the progress of diabetic complications in patients with type 2 diabetes mellitus (T2DM.Methods: We conducted a survey of 238 patients with difficult-to-control T2DM treated at a hospital in Japan using a modified behavioral economics questionnaire that included questions related to SES. The patients had been referred by general practitioners or other departments in the hospital because of poor metabolic control or unstable complications.Results: Educational attainment was significantly associated with progression of retinopathy in patients <65 years of age. Educational attainment of a high school diploma (12 years of education or lower was a significant risk factor, but there were no differences among levels of attainment beyond high school (13–16 years or more of education. Behavioral propensities were also weakly associated with complications, but not as much as educational attainment. Personal income level and economic status did not show an association with the retinopathy levels.Conclusion: Lower educational attainment is a strong risk factor for diabetic retinopathy, and it is independent of the economic status. The result suggests that cognitive function may play an important role in the progression of diabetic retinopathy in

  9. Characterizing and controlling intrinsic biases of lambda exonuclease in nascent strand sequencing reveals phasing between nucleosomes and G-quadruplex motifs around a subset of human replication origins.

    Science.gov (United States)

    Foulk, Michael S; Urban, John M; Casella, Cinzia; Gerbi, Susan A

    2015-05-01

    Nascent strand sequencing (NS-seq) is used to discover DNA replication origins genome-wide, allowing identification of features for their specification. NS-seq depends on the ability of lambda exonuclease (λ-exo) to efficiently digest parental DNA while leaving RNA-primer protected nascent strands intact. We used genomics and biochemical approaches to determine if λ-exo digests all parental DNA sequences equally. We report that λ-exo does not efficiently digest G-quadruplex (G4) structures in a plasmid. Moreover, λ-exo digestion of nonreplicating genomic DNA (LexoG0) enriches GC-rich DNA and G4 motifs genome-wide. We used LexoG0 data to control for nascent strand-independent λ-exo biases in NS-seq and validated this approach at the rDNA locus. The λ-exo-controlled NS-seq peaks are not GC-rich, and only 35.5% overlap with 6.8% of all G4s, suggesting that G4s are not general determinants for origin specification but may play a role for a subset. Interestingly, we observed a periodic spacing of G4 motifs and nucleosomes around the peak summits, suggesting that G4s may position nucleosomes at this subset of origins. Finally, we demonstrate that use of Na(+) instead of K(+) in the λ-exo digestion buffer reduced the effect of G4s on λ-exo digestion and discuss ways to increase both the sensitivity and specificity of NS-seq. © 2015 Foulk et al.; Published by Cold Spring Harbor Laboratory Press.

  10. SPIRE, a modular pipeline for eQTL analysis of RNA-Seq data, reveals a regulatory hotspot controlling miRNA expression in C. elegans.

    Science.gov (United States)

    Kel, Ivan; Chang, Zisong; Galluccio, Nadia; Romeo, Margherita; Beretta, Stefano; Diomede, Luisa; Mezzelani, Alessandra; Milanesi, Luciano; Dieterich, Christoph; Merelli, Ivan

    2016-10-18

    The interpretation of genome-wide association study is difficult, as it is hard to understand how polymorphisms can affect gene regulation, in particular for trans-regulatory elements located far from their controlling gene. Using RNA or protein expression data as phenotypes, it is possible to correlate their variations with specific genotypes. This technique is usually referred to as expression Quantitative Trait Loci (eQTLs) analysis and only few packages exist for the integration of genotype patterns and expression profiles. In particular, tools are needed for the analysis of next-generation sequencing (NGS) data on a genome-wide scale, which is essential to identify eQTLs able to control a large number of genes (hotspots). Here we present SPIRE (Software for Polymorphism Identification Regulating Expression), a generic, modular and functionally highly flexible pipeline for eQTL processing. SPIRE integrates different univariate and multivariate approaches for eQTL analysis, paying particular attention to the scalability of the procedure in order to support cis- as well as trans-mapping, thus allowing the identification of hotspots in NGS data. In particular, we demonstrated how SPIRE can handle big association study datasets, reproducing published results and improving the identification of trans-eQTLs. Furthermore, we employed the pipeline to analyse novel data concerning the genotypes of two different C. elegans strains (N2 and Hawaii) and related miRNA expression data, obtained using RNA-Seq. A miRNA regulatory hotspot was identified in chromosome 1, overlapping the transcription factor grh-1, known to be involved in the early phases of embryonic development of C. elegans. In a follow-up qPCR experiment we were able to verify most of the predicted eQTLs, as well as to show, for a novel miRNA, a significant difference in the sequences of the two analysed strains of C. elegans. SPIRE is publicly available as open source software at , together with some example

  11. Neuroimaging meta-analysis of cannabis use studies reveals convergent functional alterations in brain regions supporting cognitive control and reward processing.

    Science.gov (United States)

    Yanes, Julio A; Riedel, Michael C; Ray, Kimberly L; Kirkland, Anna E; Bird, Ryan T; Boeving, Emily R; Reid, Meredith A; Gonzalez, Raul; Robinson, Jennifer L; Laird, Angela R; Sutherland, Matthew T

    2018-03-01

    Lagging behind rapid changes to state laws, societal views, and medical practice is the scientific investigation of cannabis's impact on the human brain. While several brain imaging studies have contributed important insight into neurobiological alterations linked with cannabis use, our understanding remains limited. Here, we sought to delineate those brain regions that consistently demonstrate functional alterations among cannabis users versus non-users across neuroimaging studies using the activation likelihood estimation meta-analysis framework. In ancillary analyses, we characterized task-related brain networks that co-activate with cannabis-affected regions using data archived in a large neuroimaging repository, and then determined which psychological processes may be disrupted via functional decoding techniques. When considering convergent alterations among users, decreased activation was observed in the anterior cingulate cortex, which co-activated with frontal, parietal, and limbic areas and was linked with cognitive control processes. Similarly, decreased activation was observed in the dorsolateral prefrontal cortex, which co-activated with frontal and occipital areas and linked with attention-related processes. Conversely, increased activation among users was observed in the striatum, which co-activated with frontal, parietal, and other limbic areas and linked with reward processing. These meta-analytic outcomes indicate that cannabis use is linked with differential, region-specific effects across the brain.

  12. The Role of Water Distribution Controlled by Transmembrane Potentials in the Cytochrome c-Cardiolipin Interaction: Revealing from Surface-Enhanced Infrared Absorption Spectroscopy.

    Science.gov (United States)

    Zeng, Li; Wu, Lie; Liu, Li; Jiang, Xiue

    2017-11-02

    The interaction of cytochrome c (cyt c) with cardiolipin (CL) plays a crucial role in apoptotic functions, however, the changes of the transmembrane potential in governing the protein behavior at the membrane-water interface have not been studied due to the difficulties in simultaneously monitoring the interaction and regulating the electric field. Herein, surface-enhanced infrared absorption (SEIRA) spectroelectrochemistry is employed to study the mechanism of how the transmembrane potentials control the interaction of cyt c with CL membranes by regulating the electrode potentials of an Au film. When the transmembrane potential decreases, the water content at the interface of the membranes can be increased to slow down protein adsorption through decreasing the hydrogen-bond and hydrophobic interactions, but regulates the redox behavior of CL-bound cyt c through a possible water-facilitated proton-coupled electron transfer process. Our results suggest that the potential drop-induced restructure of the CL conformation and the hydration state could modify the structure and function of CL-bound cyt c on the lipid membrane. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. A gloomy picture: a meta-analysis of randomized controlled trials reveals disappointing effectiveness of programs aiming at preventing child maltreatment.

    Science.gov (United States)

    Euser, Saskia; Alink, Lenneke Ra; Stoltenborgh, Marije; Bakermans-Kranenburg, Marian J; van IJzendoorn, Marinus H

    2015-10-18

    Consistent findings about the effectiveness of parent programs to prevent or reduce child maltreatment are lacking. In the present meta-analysis we synthesized findings from 27 independent samples from randomized controlled trials (RCTs) on the effectiveness of 20 different intervention programs aimed at (i) preventing the occurrence of child maltreatment in the general population or with at-risk but non-maltreating families, or (ii) reducing the incidence of child maltreatment in maltreating families. A significant combined effect on maltreatment (d = 0.13; N = 4883) disappeared after the trim-and-fill approach that takes into account publication bias against smaller studies without significant outcomes. However, moderator analyses showed that larger effect sizes were found for more recent studies, studies with smaller samples, programs that provide parent training instead of only support, programs that target maltreating instead of at-risk families, and programs with a moderate length (6-12 months) or a moderate number of sessions (16-30). More RCTs are needed to further unravel which factors are associated with program effectiveness. Because currently existing programs appeared to only reduce and not prevent child maltreatment, efforts in the field of preventive intervention should also focus on the development and testing of preventive programs for families at risk for child maltreatment.

  14. Mass spectrometry profiling reveals altered plasma levels of monohydroxy fatty acids and related lipids in healthy humans after controlled exposure to biodiesel exhaust.

    Science.gov (United States)

    Gouveia-Figueira, Sandra; Karimpour, Masoumeh; Bosson, Jenny A; Blomberg, Anders; Unosson, Jon; Sehlstedt, Maria; Pourazar, Jamshid; Sandström, Thomas; Behndig, Annelie F; Nording, Malin L

    2018-08-14

    Experimental human exposure studies are an effective tool to study adverse health effects from acute inhalation of particulate matter and other constituents of air pollution. In this randomized and double-blinded crossover study, we investigated the systemic effect on bioactive lipid metabolite levels after controlled biodiesel exhaust exposure of healthy humans and compared it to filtered air at a separate exposure occasion. Eicosanoids and other oxylipins, as well as endocannabinoids and related lipids, were quantified in plasma from 14 healthy volunteers at baseline and at three subsequent time points (2, 6, and 24 h) after 1 h exposure sessions. Protocols based on liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) methods were developed to detect temporal changes in circulating levels after biodiesel exhaust exposure. The exhaust was generated by a diesel engine fed with an undiluted rapeseed methyl ester fuel. Among the 51 analyzed lipid metabolites, PGF 2α , 9,10-DiHOME, 9-HODE, 5-HETE, 11-HETE, 12-HETE, and DEA displayed significant responsiveness to the biodiesel exhaust exposure as opposed to filtered air. Of these, 9-HODE and 5-HETE at 24 h survived the 10% false discovery rate cutoff (p emphasis on metabolites with inflammation related properties and implications on cardiovascular health and disease. These observations aid future investigations on air pollution effects, especially with regard to cardiovascular outcomes. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. A 667 year record of coseismic and interseismic Coulomb stress changes in central Italy reveals the role of fault interaction in controlling irregular earthquake recurrence intervals

    Science.gov (United States)

    Wedmore, L. N. J.; Faure Walker, J. P.; Roberts, G. P.; Sammonds, P. R.; McCaffrey, K. J. W.; Cowie, P. A.

    2017-07-01

    Current studies of fault interaction lack sufficiently long earthquake records and measurements of fault slip rates over multiple seismic cycles to fully investigate the effects of interseismic loading and coseismic stress changes on the surrounding fault network. We model elastic interactions between 97 faults from 30 earthquakes since 1349 A.D. in central Italy to investigate the relative importance of co-seismic stress changes versus interseismic stress accumulation for earthquake occurrence and fault interaction. This region has an exceptionally long, 667 year record of historical earthquakes and detailed constraints on the locations and slip rates of its active normal faults. Of 21 earthquakes since 1654, 20 events occurred on faults where combined coseismic and interseismic loading stresses were positive even though 20% of all faults are in "stress shadows" at any one time. Furthermore, the Coulomb stress on the faults that experience earthquakes is statistically different from a random sequence of earthquakes in the region. We show how coseismic Coulomb stress changes can alter earthquake interevent times by 103 years, and fault length controls the intensity of this effect. Static Coulomb stress changes cause greater interevent perturbations on shorter faults in areas characterized by lower strain (or slip) rates. The exceptional duration and number of earthquakes we model enable us to demonstrate the importance of combining long earthquake records with detailed knowledge of fault geometries, slip rates, and kinematics to understand the impact of stress changes in complex networks of active faults.

  16. Combating a Global Threat to a Clonal Crop: Banana Black Sigatoka Pathogen Pseudocercospora fijiensis (Synonym Mycosphaerella fijiensis Genomes Reveal Clues for Disease Control.

    Directory of Open Access Journals (Sweden)

    Rafael E Arango Isaza

    2016-08-01

    Full Text Available Black Sigatoka or black leaf streak disease, caused by the Dothideomycete fungus Pseudocercospora fijiensis (previously: Mycosphaerella fijiensis, is the most significant foliar disease of banana worldwide. Due to the lack of effective host resistance, management of this disease requires frequent fungicide applications, which greatly increase the economic and environmental costs to produce banana. Weekly applications in most banana plantations lead to rapid evolution of fungicide-resistant strains within populations causing disease-control failures throughout the world. Given its extremely high economic importance, two strains of P. fijiensis were sequenced and assembled with the aid of a new genetic linkage map. The 74-Mb genome of P. fijiensis is massively expanded by LTR retrotransposons, making it the largest genome within the Dothideomycetes. Melting-curve assays suggest that the genomes of two closely related members of the Sigatoka disease complex, P. eumusae and P. musae, also are expanded. Electrophoretic karyotyping and analyses of molecular markers in P. fijiensis field populations showed chromosome-length polymorphisms and high genetic diversity. Genetic differentiation was also detected using neutral markers, suggesting strong selection with limited gene flow at the studied geographic scale. Frequencies of fungicide resistance in fungicide-treated plantations were much higher than those in untreated wild-type P. fijiensis populations. A homologue of the Cladosporium fulvum Avr4 effector, PfAvr4, was identified in the P. fijiensis genome. Infiltration of the purified PfAVR4 protein into leaves of the resistant banana variety Calcutta 4 resulted in a hypersensitive-like response. This result suggests that Calcutta 4 could carry an unknown resistance gene recognizing PfAVR4. Besides adding to our understanding of the overall Dothideomycete genome structures, the P. fijiensis genome will aid in developing fungicide treatment schedules

  17. Combating a Global Threat to a Clonal Crop: Banana Black Sigatoka Pathogen Pseudocercospora fijiensis (Synonym Mycosphaerella fijiensis) Genomes Reveal Clues for Disease Control.

    Science.gov (United States)

    Arango Isaza, Rafael E; Diaz-Trujillo, Caucasella; Dhillon, Braham; Aerts, Andrea; Carlier, Jean; Crane, Charles F; V de Jong, Tristan; de Vries, Ineke; Dietrich, Robert; Farmer, Andrew D; Fortes Fereira, Claudia; Garcia, Suzana; Guzman, Mauricio; Hamelin, Richard C; Lindquist, Erika A; Mehrabi, Rahim; Quiros, Olman; Schmutz, Jeremy; Shapiro, Harris; Reynolds, Elizabeth; Scalliet, Gabriel; Souza, Manoel; Stergiopoulos, Ioannis; Van der Lee, Theo A J; De Wit, Pierre J G M; Zapater, Marie-Françoise; Zwiers, Lute-Harm; Grigoriev, Igor V; Goodwin, Stephen B; Kema, Gert H J

    2016-08-01

    Black Sigatoka or black leaf streak disease, caused by the Dothideomycete fungus Pseudocercospora fijiensis (previously: Mycosphaerella fijiensis), is the most significant foliar disease of banana worldwide. Due to the lack of effective host resistance, management of this disease requires frequent fungicide applications, which greatly increase the economic and environmental costs to produce banana. Weekly applications in most banana plantations lead to rapid evolution of fungicide-resistant strains within populations causing disease-control failures throughout the world. Given its extremely high economic importance, two strains of P. fijiensis were sequenced and assembled with the aid of a new genetic linkage map. The 74-Mb genome of P. fijiensis is massively expanded by LTR retrotransposons, making it the largest genome within the Dothideomycetes. Melting-curve assays suggest that the genomes of two closely related members of the Sigatoka disease complex, P. eumusae and P. musae, also are expanded. Electrophoretic karyotyping and analyses of molecular markers in P. fijiensis field populations showed chromosome-length polymorphisms and high genetic diversity. Genetic differentiation was also detected using neutral markers, suggesting strong selection with limited gene flow at the studied geographic scale. Frequencies of fungicide resistance in fungicide-treated plantations were much higher than those in untreated wild-type P. fijiensis populations. A homologue of the Cladosporium fulvum Avr4 effector, PfAvr4, was identified in the P. fijiensis genome. Infiltration of the purified PfAVR4 protein into leaves of the resistant banana variety Calcutta 4 resulted in a hypersensitive-like response. This result suggests that Calcutta 4 could carry an unknown resistance gene recognizing PfAVR4. Besides adding to our understanding of the overall Dothideomycete genome structures, the P. fijiensis genome will aid in developing fungicide treatment schedules to combat this

  18. cAMP control of HCN2 channel Mg2+ block reveals loose coupling between the cyclic nucleotide-gating ring and the pore.

    Directory of Open Access Journals (Sweden)

    Alex K Lyashchenko

    Full Text Available Hyperpolarization-activated cyclic nucleotide-regulated HCN channels underlie the Na+-K+ permeable IH pacemaker current. As with other voltage-gated members of the 6-transmembrane KV channel superfamily, opening of HCN channels involves dilation of a helical bundle formed by the intracellular ends of S6 albeit this is promoted by inward, not outward, displacement of S4. Direct agonist binding to a ring of cyclic nucleotide-binding sites, one of which lies immediately distal to each S6 helix, imparts cAMP sensitivity to HCN channel opening. At depolarized potentials, HCN channels are further modulated by intracellular Mg2+ which blocks the open channel pore and blunts the inhibitory effect of outward K+ flux. Here, we show that cAMP binding to the gating ring enhances not only channel opening but also the kinetics of Mg2+ block. A combination of experimental and simulation studies demonstrates that agonist acceleration of block is mediated via acceleration of the blocking reaction itself rather than as a secondary consequence of the cAMP enhancement of channel opening. These results suggest that the activation status of the gating ring and the open state of the pore are not coupled in an obligate manner (as required by the often invoked Monod-Wyman-Changeux allosteric model but couple more loosely (as envisioned in a modular model of protein activation. Importantly, the emergence of second messenger sensitivity of open channel rectification suggests that loose coupling may have an unexpected consequence: it may endow these erstwhile "slow" channels with an ability to exert voltage and ligand-modulated control over cellular excitability on the fastest of physiologically relevant time scales.

  19. Potentiation of motor sub-networks for motor control but not working memory: Interaction of dACC and SMA revealed by resting-state directed functional connectivity

    Science.gov (United States)

    Diwadkar, Vaibhav A.; Asemi, Avisa; Burgess, Ashley; Chowdury, Asadur; Bressler, Steven L.

    2017-01-01

    The dorsal Anterior Cingulate Cortex (dACC) and the Supplementary Motor Area (SMA) are known to interact during motor coordination behavior. We previously discovered that the directional influences underlying this interaction in a visuo-motor coordination task are asymmetric, with the dACC→SMA influence being significantly greater than that in the reverse direction. To assess the specificity of this effect, here we undertook an analysis of the interaction between dACC and SMA in two distinct contexts. In addition to the motor coordination task, we also assessed these effects during a (n-back) working memory task. We applied directed functional connectivity analysis to these two task paradigms, and also to the rest condition of each paradigm, in which rest blocks were interspersed with task blocks. We report here that the previously known asymmetric interaction between dACC and SMA, with dACC→SMA dominating, was significantly larger in the motor coordination task than the memory task. Moreover the asymmetry between dACC and SMA was reversed during the rest condition of the motor coordination task, but not of the working memory task. In sum, the dACC→SMA influence was significantly greater in the motor task than the memory task condition, and the SMA→dACC influence was significantly greater in the motor rest than the memory rest condition. We interpret these results as suggesting that the potentiation of motor sub-networks during the motor rest condition supports the motor control of SMA by dACC during the active motor task condition. PMID:28278267

  20. Controls on the long term earthquake behavior of an intraplate fault revealed by U-Th and stable isotope analyses of syntectonic calcite veins

    Science.gov (United States)

    Williams, Randolph; Goodwin, Laurel; Sharp, Warren; Mozley, Peter

    2017-04-01

    U-Th dates on calcite precipitated in coseismic extension fractures in the Loma Blanca normal fault zone, Rio Grande rift, NM, USA, constrain earthquake recurrence intervals from 150-565 ka. This is the longest direct record of seismicity documented for a fault in any tectonic environment. Combined U-Th and stable isotope analyses of these calcite veins define 13 distinct earthquake events. These data show that for more than 400 ka the Loma Blanca fault produced earthquakes with a mean recurrence interval of 40 ± 7 ka. The coefficient of variation for these events is 0.40, indicating strongly periodic seismicity consistent with a time-dependent model of earthquake recurrence. Stochastic statistical analyses further validate the inference that earthquake behavior on the Loma Blanca was time-dependent. The time-dependent nature of these earthquakes suggests that the seismic cycle was fundamentally controlled by a stress renewal process. However, this periodic cycle was punctuated by an episode of clustered seismicity at 430 ka. Recurrence intervals within the earthquake cluster were as low as 5-11 ka. Breccia veins formed during this episode exhibit carbon isotope signatures consistent with having formed through pronounced degassing of a CO2 charged brine during post-failure, fault-localized fluid migration. The 40 ka periodicity of the long-term earthquake record of the Loma Blanca fault is similar in magnitude to recurrence intervals documented through paleoseismic studies of other normal faults in the Rio Grande rift and Basin and Range Province. We propose that it represents a background rate of failure in intraplate extension. The short-term, clustered seismicity that occurred on the fault records an interruption of the stress renewal process, likely by elevated fluid pressure in deeper structural levels of the fault, consistent with fault-valve behavior. The relationship between recurrence interval and inferred fluid degassing suggests that pore fluid pressure

  1. New Nordic Diet versus Average Danish Diet: A Randomized Controlled Trial Revealed Healthy Long-Term Effects of the New Nordic Diet by GC-MS Blood Plasma Metabolomics.

    Science.gov (United States)

    Khakimov, Bekzod; Poulsen, Sanne Kellebjerg; Savorani, Francesco; Acar, Evrim; Gürdeniz, Gözde; Larsen, Thomas M; Astrup, Arne; Dragsted, Lars O; Engelsen, Søren Balling

    2016-06-03

    A previous study has shown effects of the New Nordic Diet (NND) to stimulate weight loss and lower systolic and diastolic blood pressure in obese Danish women and men in a randomized, controlled dietary intervention study. This work demonstrates long-term metabolic effects of the NND as compared with an Average Danish Diet (ADD) in blood plasma and reveals associations between metabolic changes and health beneficial effects of the NND including weight loss. A total of 145 individuals completed the intervention and blood samples were taken along with clinical examinations before the intervention started (week 0) and after 12 and 26 weeks. The plasma metabolome was measured using GC-MS, and the final metabolite table contained 144 variables. Significant and novel metabolic effects of the diet, resulting weight loss, gender, and intervention study season were revealed using PLS-DA and ASCA. Several metabolites reflecting specific differences in the diets, especially intake of plant foods and seafood, and in energy metabolism related to ketone bodies and gluconeogenesis formed the predominant metabolite pattern discriminating the intervention groups. Among NND subjects, higher levels of vaccenic acid and 3-hydroxybutanoic acid were related to a higher weight loss, while higher concentrations of salicylic, lactic, and N-aspartic acids and 1,5-anhydro-d-sorbitol were related to a lower weight loss. Specific gender and seasonal differences were also observed. The study strongly indicates that healthy diets high in fish, vegetables, fruit, and whole grain facilitated weight loss and improved insulin sensitivity by increasing ketosis and gluconeogenesis in the fasting state.

  2. Titan Casts Revealing Shadow

    Science.gov (United States)

    2004-05-01

    A rare celestial event was captured by NASA's Chandra X-ray Observatory as Titan -- Saturn's largest moon and the only moon in the Solar System with a thick atmosphere -- crossed in front of the X-ray bright Crab Nebula. The X-ray shadow cast by Titan allowed astronomers to make the first X-ray measurement of the extent of its atmosphere. On January 5, 2003, Titan transited the Crab Nebula, the remnant of a supernova explosion that was observed to occur in the year 1054. Although Saturn and Titan pass within a few degrees of the Crab Nebula every 30 years, they rarely pass directly in front of it. "This may have been the first transit of the Crab Nebula by Titan since the birth of the Crab Nebula," said Koji Mori of Pennsylvania State University in University Park, and lead author on an Astrophysical Journal paper describing these results. "The next similar conjunction will take place in the year 2267, so this was truly a once in a lifetime event." Animation of Titan's Shadow on Crab Nebula Animation of Titan's Shadow on Crab Nebula Chandra's observation revealed that the diameter of the X-ray shadow cast by Titan was larger than the diameter of its solid surface. The difference in diameters gives a measurement of about 550 miles (880 kilometers) for the height of the X-ray absorbing region of Titan's atmosphere. The extent of the upper atmosphere is consistent with, or slightly (10-15%) larger, than that implied by Voyager I observations made at radio, infrared, and ultraviolet wavelengths in 1980. "Saturn was about 5% closer to the Sun in 2003, so increased solar heating of Titan may account for some of this atmospheric expansion," said Hiroshi Tsunemi of Osaka University in Japan, one of the coauthors on the paper. The X-ray brightness and extent of the Crab Nebula made it possible to study the tiny X-ray shadow cast by Titan during its transit. By using Chandra to precisely track Titan's position, astronomers were able to measure a shadow one arcsecond in

  3. Characterization of a null allelic mutant of the rice NAL1 gene reveals its role in regulating cell division.

    Directory of Open Access Journals (Sweden)

    Dan Jiang

    Full Text Available Leaf morphology is closely associated with cell division. In rice, mutations in Narrow leaf 1 (NAL1 show narrow leaf phenotypes. Previous studies have shown that NAL1 plays a role in regulating vein patterning and increasing grain yield in indica cultivars, but its role in leaf growth and development remains unknown. In this report, we characterized two allelic mutants of NARROW LEAF1 (NAL1, nal1-2 and nal1-3, both of which showed a 50% reduction in leaf width and length, as well as a dwarf culm. Longitudinal and transverse histological analyses of leaves and internodes revealed that cell division was suppressed in the anticlinal orientation but enhanced in the periclinal orientation in the mutants, while cell size remained unaltered. In addition to defects in cell proliferation, the mutants showed abnormal midrib in leaves. Map-based cloning revealed that nal1-2 is a null allelic mutant of NAL1 since both the whole promoter and a 404-bp fragment in the first exon of NAL1 were deleted, and that a 6-bp fragment was deleted in the mutant nal1-3. We demonstrated that NAL1 functions in the regulation of cell division as early as during leaf primordia initiation. The altered transcript level of G1- and S-phase-specific genes suggested that NAL1 affects cell cycle regulation. Heterogeneous expression of NAL1 in fission yeast (Schizosaccharomyces pombe further supported that NAL1 affects cell division. These results suggest that NAL1 controls leaf width and plant height through its effects on cell division.

  4. Revealing the programming process

    DEFF Research Database (Denmark)

    Bennedsen, Jens; Caspersen, Michael Edelgaard

    2005-01-01

    One of the most important goals of an introductory programming course is that the students learn a systematic approach to the development of computer programs. Revealing the programming process is an important part of this; however, textbooks do not address the issue -- probably because...... the textbook medium is static and therefore ill-suited to expose the process of programming. We have found that process recordings in the form of captured narrated programming sessions are a simple, cheap, and efficient way of providing the revelation.We identify seven different elements of the programming...

  5. TypeScript revealed

    CERN Document Server

    Maharry, Dan

    2013-01-01

    TypeScript Revealed is a quick 100-page guide to Anders Hejlsberg's new take on JavaScript. With this brief, fast-paced introduction to TypeScript, .NET, Web and Windows 8 application developers who are already familiar with JavaScript will easily get up to speed with TypeScript and decide whether or not to start incorporating it into their own development. TypeScript is 'JavaScript for Application-scale development'; a superset of JavaScript that brings to it an additional object-oriented-like syntax familiar to .NET programmers that compiles down into simple, clean JavaScript that any browse

  6. Chemistry of plutonium revealed

    International Nuclear Information System (INIS)

    Connick, R.E.

    1992-01-01

    In 1941 one goal of the Manhattan Project was to unravel the chemistry of the synthetic element plutonium as rapidly as possible. In this paper the work carried out at Berkeley from the spring of 1942 to the summer of 1945 is described briefly. The aqueous chemistry of plutonium is quite remarkable. Important insights were obtained from tracer experiments, but the full complexity was not revealed until macroscopic amounts (milligrams) became available. Because processes for separation from fission products were based on aqueous solutions, such solution chemistry was emphasized, particularly precipitation and oxidation-reduction behavior. The latter turned out to be unusually intricate when it was discovered that two more oxidation states existed in aqueous solution than had previously been suspected. Further, an equilibrium was rapidly established among the four aqueous oxidation states, while at the same time any three were not in equilibrium. These and other observations made while doing a crash study of a previously unknown element are reported

  7. Android Emotions Revealed

    DEFF Research Database (Denmark)

    Vlachos, Evgenios; Schärfe, Henrik

    2012-01-01

    This work presents a method for designing facial interfaces for sociable android robots with respect to the fundamental rules of human affect expression. Extending the work of Paul Ekman towards a robotic direction, we follow the judgment-based approach for evaluating facial expressions to test...... findings are based on the results derived from a number of judgments, and suggest that before programming the facial expressions of a Geminoid, the Original should pass through the proposed procedure. According to our recommendations, the facial expressions of an android should be tested by judges, even...... in which case an android robot like the Geminoid|DK –a duplicate of an Original person- reveals emotions convincingly; when following an empirical perspective, or when following a theoretical one. The methodology includes the processes of acquiring the empirical data, and gathering feedback on them. Our...

  8. REVEAL: Software Documentation and Platform Migration

    Science.gov (United States)

    Wilson, Michael A.; Veibell, Victoir T.; Freudinger, Lawrence C.

    2008-01-01

    The Research Environment for Vehicle Embedded Analysis on Linux (REVEAL) is reconfigurable data acquisition software designed for network-distributed test and measurement applications. In development since 2001, it has been successfully demonstrated in support of a number of actual missions within NASA s Suborbital Science Program. Improvements to software configuration control were needed to properly support both an ongoing transition to operational status and continued evolution of REVEAL capabilities. For this reason the project described in this report targets REVEAL software source documentation and deployment of the software on a small set of hardware platforms different from what is currently used in the baseline system implementation. This report specifically describes the actions taken over a ten week period by two undergraduate student interns and serves as a final report for that internship. The topics discussed include: the documentation of REVEAL source code; the migration of REVEAL to other platforms; and an end-to-end field test that successfully validates the efforts.

  9. Transcriptomic analysis reveals ethylene as stimulator and auxin as regulator of adventitious root formation in petunia cuttings

    Science.gov (United States)

    Druege, Uwe; Franken, Philipp; Lischewski, Sandra; Ahkami, Amir H.; Zerche, Siegfried; Hause, Bettina; Hajirezaei, Mohammad R.

    2014-01-01

    Adventitious root (AR) formation in the stem base (SB) of cuttings is the basis for propagation of many plant species and petunia is used as model to study this developmental process. Following AR formation from 2 to 192 hours post-excision (hpe) of cuttings, transcriptome analysis by microarray revealed a change of the character of the rooting zone from SB to root identity. The greatest shift in the number of differentially expressed genes was observed between 24 and 72 hpe, when the categories storage, mineral nutrient acquisition, anti-oxidative and secondary metabolism, and biotic stimuli showed a notable high number of induced genes. Analyses of phytohormone-related genes disclosed multifaceted changes of the auxin transport system, auxin conjugation and the auxin signal perception machinery indicating a reduction in auxin sensitivity and phase-specific responses of particular auxin-regulated genes. Genes involved in ethylene biosynthesis and action showed a more uniform pattern as a high number of respective genes were generally induced during the whole process of AR formation. The important role of ethylene for stimulating AR formation was demonstrated by the application of inhibitors of ethylene biosynthesis and perception as well as of the precursor aminocyclopropane-1-carboxylic acid, all changing the number and length of AR. A model is proposed showing the putative role of polar auxin transport and resulting auxin accumulation in initiation of subsequent changes in auxin homeostasis and signal perception with a particular role of Aux/IAA expression. These changes might in turn guide the entrance into the different phases of AR formation. Ethylene biosynthesis, which is stimulated by wounding and does probably also respond to other stresses and auxin, acts as important stimulator of AR formation probably via the expression of ethylene responsive transcription factor genes, whereas the timing of different phases seems to be controlled by auxin. PMID

  10. Transcriptomic analysis reveals ethylene as stimulator and auxin as regulator of adventitious root formation in petunia cuttings.

    Science.gov (United States)

    Druege, Uwe; Franken, Philipp; Lischewski, Sandra; Ahkami, Amir H; Zerche, Siegfried; Hause, Bettina; Hajirezaei, Mohammad R

    2014-01-01

    Adventitious root (AR) formation in the stem base (SB) of cuttings is the basis for propagation of many plant species and petunia is used as model to study this developmental process. Following AR formation from 2 to 192 hours post-excision (hpe) of cuttings, transcriptome analysis by microarray revealed a change of the character of the rooting zone from SB to root identity. The greatest shift in the number of differentially expressed genes was observed between 24 and 72 hpe, when the categories storage, mineral nutrient acquisition, anti-oxidative and secondary metabolism, and biotic stimuli showed a notable high number of induced genes. Analyses of phytohormone-related genes disclosed multifaceted changes of the auxin transport system, auxin conjugation and the auxin signal perception machinery indicating a reduction in auxin sensitivity and phase-specific responses of particular auxin-regulated genes. Genes involved in ethylene biosynthesis and action showed a more uniform pattern as a high number of respective genes were generally induced during the whole process of AR formation. The important role of ethylene for stimulating AR formation was demonstrated by the application of inhibitors of ethylene biosynthesis and perception as well as of the precursor aminocyclopropane-1-carboxylic acid, all changing the number and length of AR. A model is proposed showing the putative role of polar auxin transport and resulting auxin accumulation in initiation of subsequent changes in auxin homeostasis and signal perception with a particular role of Aux/IAA expression. These changes might in turn guide the entrance into the different phases of AR formation. Ethylene biosynthesis, which is stimulated by wounding and does probably also respond to other stresses and auxin, acts as important stimulator of AR formation probably via the expression of ethylene responsive transcription factor genes, whereas the timing of different phases seems to be controlled by auxin.

  11. Transcriptomic analysis reveals ethylene as stimulator and auxin as regulator of adventitious root formation in petunia cuttings

    Directory of Open Access Journals (Sweden)

    Uwe eDruege

    2014-09-01

    Full Text Available Adventitious root (AR formation in the stem base of cuttings is the basis for propagation of many plant species and petunia is used as model to study this developmental process. Following AR formation from 2 to 192 hours after excision (hpe of cuttings, transcriptome analysis by microarray revealed a change of the character of the rooting zone from stem base to root identity. The greatest shift in the number of differentially expressed genes was observed between 24 and 72 hpe, when the categories storage, mineral nutrient acquisition, anti-oxidative and secondary metabolism, and biotic stimuli showed a notable high number of induced genes. Analyses of phytohormone-related genes disclosed multifaceted changes of the auxin transport system, auxin conjugation and the auxin signal perception machinery indicating a reduction in auxin sensitivity and phase-specific responses of particular auxin-regulated genes. Genes involved in ethylene biosynthesis and action showed a more uniform pattern as a high number of respective genes were generally induced during the whole process of AR formation. The important role of ethylene for stimulating AR formation was demonstrated by the application of inhibitors of ethylene biosynthesis and perception as well as of the precursor aminocyclopropane-1-carboxylic acid, all changing the number and length of AR. A model is proposed showing the putative role of polar auxin transport and resulting auxin accumulation in initiation of subsequent changes in auxin homeostasis and signal perception with a particular role of Aux/IAA expression. These changes might in turn guide the entrance into the different phases of AR formation. Ethylene biosynthesis, which is stimulated by wounding and does probably also respond to other stresses and auxin, acts as important stimulator of AR formation probably via the expression of ethylene responsive transcription factor genes, whereas the timing of different phases seems to be controlled

  12. Executive Semantic Processing Is Underpinned by a Large-scale Neural Network: Revealing the Contribution of Left Prefrontal, Posterior Temporal, and Parietal Cortex to Controlled Retrieval and Selection Using TMS

    Science.gov (United States)

    Whitney, Carin; Kirk, Marie; O'Sullivan, Jamie; Ralph, Matthew A. Lambon; Jefferies, Elizabeth

    2012-01-01

    To understand the meanings of words and objects, we need to have knowledge about these items themselves plus executive mechanisms that compute and manipulate semantic information in a task-appropriate way. The neural basis for semantic control remains controversial. Neuroimaging studies have focused on the role of the left inferior frontal gyrus…

  13. REVEAL: Software Documentation and Platform Migration

    Science.gov (United States)

    Wilson, Michael A.; Veibell, Victoir T.

    2011-01-01

    The Research Environment for Vehicle Embedded Analysis on Linux (REVEAL) is reconfigurable data acquisition software designed for network-distributed test and measurement applications. In development since 2001, it has been successfully demonstrated in support of a number of actual missions within NASA's Suborbital Science Program. Improvements to software configuration control were needed to properly support both an ongoing transition to operational status and continued evolution of REVEAL capabilities. For this reason the project described in this report targets REVEAL software source documentation and deployment of the software on a small set of hardware platforms different from what is currently used in the baseline system implementation. This presentation specifically describes the actions taken over a ten week period by two undergraduate student interns and serves as an overview of the content of the final report for that internship.

  14. Multiparametric analysis of host response to murine cytomegalovirus in MHC class I-disparate mice reveals primacy of Dk-licensed Ly49G2+ NK cells in viral control.

    Science.gov (United States)

    Prince, Jessica; Lundgren, Alyssa; Stadnisky, Michael D; Nash, William T; Beeber, Amira; Turner, Stephen D; Brown, Michael G

    2013-11-01

    MHC class I D(k) and Ly49G2 (G2) inhibitory receptor-expressing NK cells are essential to murine CMV (MCMV) resistance in MA/My mice. Without D(k), G2(+) NK cells in C57L mice fail to protect against MCMV infection. As a cognate ligand of G2, D(k) licenses G2(+) NK cells for effector activity. These data suggested that D(k)-licensed G2(+) NK cells might recognize and control MCMV infection. However, a role for licensed NK cells in viral immunity is uncertain. We combined classical genetics with flow cytometry to visualize the host response to MCMV. Immune cells collected from individuals of a diverse cohort of MA/My × C57L offspring segregating D(k) were examined before infection and postinfection, including Ly49(+) NK subsets, receptor expression features, and other phenotypic traits. To identify critical NK cell features, automated analysis of 110 traits was performed in R using the Pearson correlation, followed with a Bonferroni correction for multiple tests. Hierarchical clustering of trait associations and principal component analyses were used to discern shared immune response and genetic relationships. The results demonstrate that G2 expression on naive blood NK cells was predictive of MCMV resistance. However, rapid G2(+) NK cell expansion following viral exposure occurred selectively in D(k) offspring; this response was more highly correlated with MCMV control than all other immune cell features. We infer that D(k)-licensed G2(+) NK cells efficiently detected missing-self MHC cues on viral targets, which elicited cellular expansion and target cell killing. Therefore, MHC polymorphism regulates licensing and detection of viral targets by distinct subsets of NK cells required in innate viral control.

  15. Analysis of positive control STR experiments reveals that results obtained for FGA, D3S1358, and D13S317 condition the success rate of the analysis of routine reference samples.

    Science.gov (United States)

    Murigneux, Valentine; Dufour, Anne-Béatrice; Lobry, Jean R; Pène, Laurent

    2014-07-01

    About 120,000 reference samples are analyzed each year in the Forensic Laboratory of Lyon. A total of 1640 positive control experiments used to validate and optimize the analytical method in the routine process were submitted to a multivariate exploratory data analysis approach with the aim of better understanding the underlying sources of variability. The peak heights of the 16 genetic markers targeted by the AmpFℓSTR(®) Identifiler(®) STR kit were used as variables of interest. Six different 3130xl genetic analyzers located in the same controlled environment were involved. Two major sources of variability were found: (i) the DNA load of the sample modulates all peak heights in a similar way so that the 16 markers are highly correlated, (ii) the genetic analyzer used with a locus-specific response for peak height and a better sensitivity for the most recently acquired. Three markers (FGA, D3S1358, and D13S317) were found to be of special interest to predict the success rate observed in the routine process. © 2014 American Academy of Forensic Sciences.

  16. Characterization of S-Phase Specific BRCA1-Containing Complex

    National Research Council Canada - National Science Library

    You, Fanglei

    2003-01-01

    ...), was observed in HeLa and in 293 cells. Hydroxyurea treatment of cells results in the reduction of BRCA1 content in the RNA polymerase II holoenzyme complex with a complementary increase in the HUIC...

  17. Characterization of S-Phase Specific BRCA1-Containing Complex

    National Research Council Canada - National Science Library

    Chiba, Natsuko

    2002-01-01

    ...), was observed in HeLa and in 293 cells. Hydroxyurea treatment of cells results in the reduction of BRCA1 content in the RNA polymerase II holoenzyme complex with a complementary increase in the HUIC...

  18. Comprehensive analysis of the MLH1 promoter region in 480 patients with colorectal cancer and 1150 controls reveals new variants including one with a heritable constitutional MLH1 epimutation.

    Science.gov (United States)

    Morak, Monika; Ibisler, Ayseguel; Keller, Gisela; Jessen, Ellen; Laner, Andreas; Gonzales-Fassrainer, Daniela; Locher, Melanie; Massdorf, Trisari; Nissen, Anke M; Benet-Pagès, Anna; Holinski-Feder, Elke

    2018-04-01

    Germline defects in MLH1 , MSH2 , MSH6 and PMS2 predisposing for Lynch syndrome (LS) are mainly based on sequence changes, whereas a constitutional epimutation of MLH1 (CEM) is exceptionally rare. This abnormal MLH1 promoter methylation is not hereditary when arising de novo, whereas a stably heritable and variant-induced CEM was described for one single allele. We searched for MLH1 promoter variants causing a germline or somatic methylation induction or transcriptional repression. We analysed the MLH1 promoter sequence in five different patient groups with colorectal cancer (CRC) (n=480) composed of patients with i) CEM (n=16), ii) unsolved loss of MLH1 expression in CRC (n=37), iii) CpG-island methylator-phenotype CRC (n=102), iv) patients with LS (n=83) and v) MLH1-proficient CRC (n=242) as controls. 1150 patients with non-LS tumours also served as controls to correctly judge the results. We detected 10 rare MLH1 promoter variants. One novel, complex MLH1 variant c.-63_-58delins18 is present in a patient with CRC with CEM and his sister, both showing a complete allele-specific promoter methylation and transcriptional silencing. The other nine promoter variants detected in 17 individuals were not associated with methylation. For four of these, a normal, biallelic MLH1 expression was found in the patients' cDNA. We report the second promoter variant stably inducing a hereditary CEM. Concerning the classification of promoter variants, we discuss contradictory results from the literature for two variants, describe classification discrepancies between existing rules for five variants, suggest the (re-)classification of five promoter variants to (likely) benign and regard four variants as functionally unclear. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. CRISPR-Cas gene-editing reveals RsmA and RsmC act through FlhDC to repress the SdhE flavinylation factor and control motility and prodigiosin production in Serratia.

    Science.gov (United States)

    Hampton, Hannah G; McNeil, Matthew B; Paterson, Thomas J; Ney, Blair; Williamson, Neil R; Easingwood, Richard A; Bostina, Mihnea; Salmond, George P C; Fineran, Peter C

    2016-06-01

    SdhE is required for the flavinylation and activation of succinate dehydrogenase and fumarate reductase (FRD). In addition, SdhE is conserved in proteobacteria (α, β and γ) and eukaryotes. Although the function of this recently characterized family of proteins has been determined, almost nothing is known about how their genes are regulated. Here, the RsmA (CsrA) and RsmC (HexY) post-transcriptional and post-translational regulators have been identified and shown to repress sdhEygfX expression in Serratia sp. ATCC 39006. Conversely, the flagella master regulator complex, FlhDC, activated sdhEygfX transcription. To investigate the hierarchy of control, we developed a novel approach that utilized endogenous CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR associated) genome-editing by a type I-F system to generate a chromosomal point mutation in flhC. Mutation of flhC alleviated the ability of RsmC to repress sdhEygfX expression, whereas RsmA acted in both an FlhDC-dependent and -independent manner to inhibit sdhEygfX. Mutation of rsmA or rsmC, or overexpression of FlhDC, led to increased prodigiosin, biosurfactant, swimming and swarming. Consistent with the modulation of sdhE by motility regulators, we have demonstrated that SdhE and FRD are required for maximal flagella-dependent swimming. Together, these results demonstrate that regulators of both metabolism and motility (RsmA, RsmC and FlhDC) control the transcription of the sdhEygfX operon.

  20. Transcriptional analysis of abdominal fat in chickens divergently selected on bodyweight at two ages reveals novel mechanisms controlling adiposity: validating visceral adipose tissue as a dynamic endocrine and metabolic organ.

    Science.gov (United States)

    Resnyk, C W; Carré, W; Wang, X; Porter, T E; Simon, J; Le Bihan-Duval, E; Duclos, M J; Aggrey, S E; Cogburn, L A

    2017-08-16

    Decades of intensive genetic selection in the domestic chicken (Gallus gallus domesticus) have enabled the remarkable rapid growth of today's broiler (meat-type) chickens. However, this enhanced growth rate was accompanied by several unfavorable traits (i.e., increased visceral fatness, leg weakness, and disorders of metabolism and reproduction). The present descriptive analysis of the abdominal fat transcriptome aimed to identify functional genes and biological pathways that likely contribute to an extreme difference in visceral fatness of divergently selected broiler chickens. We used the Del-Mar 14 K Chicken Integrated Systems microarray to take time-course snapshots of global gene transcription in abdominal fat of juvenile [1-11 weeks of age (wk)] chickens divergently selected on bodyweight at two ages (8 and 36 wk). Further, a RNA sequencing analysis was completed on the same abdominal fat samples taken from high-growth (HG) and low-growth (LG) cockerels at 7 wk, the age with the greatest divergence in body weight (3.2-fold) and visceral fatness (19.6-fold). Time-course microarray analysis revealed 312 differentially expressed genes (FDR ≤ 0.05) as the main effect of genotype (HG versus LG), 718 genes in the interaction of age and genotype, and 2918 genes as the main effect of age. The RNA sequencing analysis identified 2410 differentially expressed genes in abdominal fat of HG versus LG chickens at 7 wk. The HG chickens are fatter and over-express numerous genes that support higher rates of visceral adipogenesis and lipogenesis. In abdominal fat of LG chickens, we found higher expression of many genes involved in hemostasis, energy catabolism and endocrine signaling, which likely contribute to their leaner phenotype and slower growth. Many transcription factors and their direct target genes identified in HG and LG chickens could be involved in their divergence in adiposity and growth rate. The present analyses of the visceral fat transcriptome in

  1. Structural controls on fluid circulation at the Caviahue-Copahue Volcanic Complex (CCVC) geothermal area (Chile-Argentina), revealed by soil CO2 and temperature, self-potential, and helium isotopes

    Science.gov (United States)

    Roulleau, Emilie; Bravo, Francisco; Pinti, Daniele L.; Barde-Cabusson, Stéphanie; Pizarro, Marcela; Tardani, Daniele; Muñoz, Carlos; Sanchez, Juan; Sano, Yuji; Takahata, Naoto; de la Cal, Federico; Esteban, Carlos; Morata, Diego

    2017-07-01

    Natural geothermal systems are limited areas characterized by anomalously high heat flow caused by recent tectonic or magmatic activity. The heat source at depth is the result of the emplacement of magma bodies, controlled by the regional volcano-tectonic setting. In contrast, at a local scale a well-developed fault-fracture network favors the development of hydrothermal cells, and promotes the vertical advection of fluids and heat. The Southern Volcanic Zone (SVZ), straddling Chile and Argentina, has an important, yet unexplored and undeveloped geothermal potential. Studies on the lithological and tectonic controls of the hydrothermal circulation are therefore important for a correct assessment of the geothermal potential of the region. Here, new and dense self-potential (SP), soil CO2 and temperature (T) measurements, and helium isotope data measured in fumaroles and thermal springs from the geothermal area located in the north-eastern flank of the Copahue volcanic edifice, within the Caviahue Caldera (the Caviahue-Copahue Volcanic Complex - CCVC) are presented. Our results allowed to the constraint of the structural origin of the active thermal areas and the understanding of the evolution of the geothermal system. NE-striking faults in the area, characterized by a combination of SP, CO2, and T maxima and high 3He/4He ratios (up to 8.16 ± 0.21Ra, whereas atmospheric Ra is 1.382 × 10- 6), promote the formation of vertical permeability preferential pathways for fluid circulation. WNW-striking faults represent low-permeability pathways for hydrothermal fluid ascent, but promote infiltration of meteoric water at shallow depths, which dilute the hydrothermal input. The region is scattered with SP, CO2, and T minima, representing self-sealed zones characterized by impermeable altered rocks at depth, which create local barriers for fluid ascent. The NE-striking faults seem to be associated with the upflowing zones of the geothermal system, where the boiling process

  2. Characterization of the CrbS/R Two-Component System in Pseudomonas fluorescens Reveals a New Set of Genes under Its Control and a DNA Motif Required for CrbR-Mediated Transcriptional Activation

    Directory of Open Access Journals (Sweden)

    Edgardo Sepulveda

    2017-11-01

    Full Text Available The CrbS/R system is a two-component signal transduction system that regulates acetate utilization in Vibrio cholerae, P. aeruginosa, and P. entomophila. CrbS is a hybrid histidine kinase that belongs to a recently identified family, in which the signaling domain is fused to an SLC5 solute symporter domain through aSTAC domain. Upon activation by CrbS, CrbR activates transcription of the acs gene, which encodes an acetyl-CoA synthase (ACS, and the actP gene, which encodes an acetate/solute symporter. In this work, we characterized the CrbS/R system in Pseudomonas fluorescens SBW25. Through the quantitative proteome analysis of different mutants, we were able to identify a new set of genes under its control, which play an important role during growth on acetate. These results led us to the identification of a conserved DNA motif in the putative promoter region of acetate-utilization genes in the Gammaproteobacteria that is essential for the CrbR-mediated transcriptional activation of genes under acetate-utilizing conditions. Finally, we took advantage of the existence of a second SLC5-containing two-component signal transduction system in P. fluorescens, CbrA/B, to demonstrate that the activation of the response regulator by the histidine kinase is not dependent on substrate transport through the SLC5 domain.

  3. Three-Dimensional Spatiotemporal Modeling of Colon Cancer Organoids Reveals that Multimodal Control of Stem Cell Self-Renewal is a Critical Determinant of Size and Shape in Early Stages of Tumor Growth.

    Science.gov (United States)

    Yan, Huaming; Konstorum, Anna; Lowengrub, John S

    2018-05-01

    We develop a three-dimensional multispecies mathematical model to simulate the growth of colon cancer organoids containing stem, progenitor and terminally differentiated cells, as a model of early (prevascular) tumor growth. Stem cells (SCs) secrete short-range self-renewal promoters (e.g., Wnt) and their long-range inhibitors (e.g., Dkk) and proliferate slowly. Committed progenitor (CP) cells proliferate more rapidly and differentiate to produce post-mitotic terminally differentiated cells that release differentiation promoters, forming negative feedback loops on SC and CP self-renewal. We demonstrate that SCs play a central role in normal and cancer colon organoids. Spatial patterning of the SC self-renewal promoter gives rise to SC clusters, which mimic stem cell niches, around the organoid surface, and drive the development of invasive fingers. We also study the effects of externally applied signaling factors. Applying bone morphogenic proteins, which inhibit SC and CP self-renewal, reduces invasiveness and organoid size. Applying hepatocyte growth factor, which enhances SC self-renewal, produces larger sizes and enhances finger development at low concentrations but suppresses fingers at high concentrations. These results are consistent with recent experiments on colon organoids. Because many cancers are hierarchically organized and are subject to feedback regulation similar to that in normal tissues, our results suggest that in cancer, control of cancer stem cell self-renewal should influence the size and shape in similar ways, thereby opening the door to novel therapies.

  4. Sedimentological processes in a scarp-controlled rocky shoreline to upper continental slope environment, as revealed by unusual sedimentary features in the Neogene Coquimbo Formation, north-central Chile

    Science.gov (United States)

    Le Roux, J. P.; Gómez, Carolina; Fenner, Juliane; Middleton, Heather

    2004-03-01

    Exceptionally good outcrops of Miocene to Pliocene deposits in the vicinity of submarine Paleozoic basement scarps at Carrizalillo, north of La Serena, reveal a wealth of sedimentary features not commonly observed. The most proximal facies consist of rock fall and coarse-grained debris flow deposits directly abutting the basement wall from which they originated. Angular basement clasts are mixed with well-rounded cobbles, which probably formed as a basal gravel on a wave-cut platform at the beginning of marine flooding, subsequently accumulated at the scarp edge and were incorporated into the debris when the latter collapsed. The poor sorting, inverse grading, and protruding cobbles and boulders are classical debris flow features, with good clast imbrication indicating a laminar shearing action. A medial facies is represented by secondary channels running parallel to the major scarp about 1 km downslope of the first locality. In the largest channel, megaflutes at the base indicate the passage of highly turbulent, nondepositing flows eroding the soft, silty substrate. In the deepest, central part of the channel, a pebbly coquina shows horizontal and trough cross-stratification, with most of the bivalves oriented convex side up. Meter-scale rip-up clasts of the underlying siltstone are also present, indicating turbulent flow with a density sufficiently high to retard settling. The coquina is interpreted as a detachment deposit resulting from a hydroplaning debris flow along the central part of the channel, where the velocity and rate of pore pressure decay were highest. This deposit is overlain by fining upward, massive to horizontally stratified sandstone very similar in texture and composition to the matrix of the debris flow, suggesting its formation by surface transformation and elutriation of the latter. Along the channel margin, a basal centimeter-scale sandstone layer is virtually unaffected by the megaflute topography and clearly represents a subsequent event

  5. Genetic variation in pea (Pisum sativum L.) demonstrates the importance of root but not shoot C/N ratios in the control of plant morphology and reveals a unique relationship between shoot length and nodulation intensity.

    Science.gov (United States)

    Ludidi, Ndiko N; Pellny, Till K; Kiddle, Guy; Dutilleul, Christelle; Groten, Karin; VAN Heerden, Philippus D R; Dutt, Som; Powers, Stephen J; Römer, Peter; Foyer, Christine H

    2007-10-01

    Nodule numbers are regulated through systemic auto-regulatory signals produced by shoots and roots. The relative effects of shoot and root genotype on nodule numbers together with relationships to organ biomass, carbon (C) and nitrogen (N) status, and related parameters were measured in pea (Pisum sativum) exploiting natural genetic variation in maturity and apparent nodulation intensity. Reciprocal grafting experiments between the early (Athos), intermediate (Phönix) and late (S00182) maturity phenotypes were performed and Pearson's correlation coefficients for the parameters were calculated. No significant correlations were found between shoot C/N ratios and plant morphology parameters, but the root C/N ratio showed a strong correlation with root fresh and dry weights as well as with shoot fresh weight with less significant interactions with leaf number. Hence, the root C/N ratio rather than shoot C/N had a predominant influence on plant morphology when pea plants are grown under conditions of symbiotic nitrogen supply. The only phenotypic characteristic that showed a statistically significant correlation with nodulation intensity was shoot length, which accounted for 68.5% of the variation. A strong linear relationship was demonstrated between shoot length and nodule numbers. Hence, pea nodule numbers are controlled by factors related to shoot extension, but not by shoot or root biomass accumulation, total C or total N. The relationship between shoot length and nodule numbers persisted under field conditions. These results suggest that stem height could be used as a breeding marker for the selection of pea cultivars with high nodule numbers and high seed N contents.

  6. Comparative mapping reveals similar linkage of functional genes to ...

    Indian Academy of Sciences (India)

    genes between O. sativa and B. napus may have consistent function and control similar traits, which may be ..... acea chromosomes reveals islands of conserved organization. ... 1998 Conserved structure and function of the Arabidopsis flow-.

  7. Imaging beneath the skin of large tropical rivers: Clay controls on system morphodynamics revealed by novel CHIRP sub-surface sonar and deep coring along the Fly and Strickland Rivers, Papua New Guinea (Invited)

    Science.gov (United States)

    Aalto, R. E.; Grenfell, M.; Lauer, J. W.

    2010-12-01

    , where the channel traverses a clay bed, with minimal evident bedforms and giant scour holes carved 35m deep into clay at INNER apexes of the peculiar dog-leg meander bends; 3) Hard (old) clay ridges & an intervening channel network buried ~15m below the current bed of Lake Murray, indicating a ~10m rise in the Strickland River near that location; 4) A survey up newly formed rapids through a head-cut crevasse splay (though a recently buried forest) joining the Mamboi River to the middle Strickland River, the pathway for a pending avulsion; 5) The prevalence of clay in many of our deep cores throughout the Strickland, Fly, and Lake Murray floodplains; and 6) an example of the rapid infilling of a recent oxbow cutoff by clay deposition. It appears that clay (and peat) units dominate the floodplains and large portions of the channel bed. Furthermore, this clay often appears to control the morphodynamics of the channel, from the head-cut clay knick points of the pending avulsion, to many frozen meander bends, to the unusual dog-leg meanders of the lower Middle Fly River. We conclude with a synthesis of how clay deposition can potentially play a major role in orchestrating the channel morphodynamics of large tropical rivers.

  8. Tectonic/climatic control on sediment provenance in the Cape Roberts Project core record (southern Victoria Land, Antarctica): A pulsing late Oligocene/early Miocene signal from south revealed by detrital thermochronology

    Science.gov (United States)

    Olivetti, V.; Balestrieri, M. L.; Rossetti, F.; Talarico, F. M.

    2012-04-01

    , three peaks are detected reflecting different bedrock provenance areas. Two peaks older than 40 Ma (P2 and P3) are compatible with thermochronological data from TAM bedrock that underwent a stepwise denudation in Cretaceous times. A Peak younger than 40 Ma (P1) has been detected occasionally, recording the signal of a source area exhumed during late Oligocene /early Miocene with a constant denudation rate of 0.4 mm/yr (constant lag-time up-section), but absent in the onshore portion of the proximal TAM. Indeed, when compared with AFT data from ANDRILL cores, the relatively young P1 ages, suggest that part of sediments in the Cape Robert Rift basin have a provenance from source regions probably located far away in the south (i.e. Skelton-Byrd glaciers region) where bedrock experienced compatible thermal histories. This provenance would imply glacial systems with main flow patterns from south to the north, therefore orthogonal to the orientation of present-day drainage. We thus infer that the post-Eocene glacial and erosional history of the TAM front was significantly controlled by the N-S-trending transtensional regime that affected the western Ross Sea margin during transition from orthogonal to oblique rifting in the region. The appearance and disappearance of P1 along the drill-cored stratigraphic succession seems to be linked to the oscillation in the extent of the ice sheet.

  9. Revealed preference with limited consideration

    NARCIS (Netherlands)

    Demuynck, T.; Seel, C.

    2014-01-01

    We derive revealed preference tests for models where individuals use consideration sets to simplify their consumption problem. Our basic test provides necessary and sufficient conditions for consistency of observed choices with the existence of consideration set restrictions. The same conditions can

  10. Decision Making and Revealed Preference

    DEFF Research Database (Denmark)

    de la Rosa, Leonidas Enrique

    If our decision-making processes are to some extent shaped by evolutionary pressures and our environment is different from that to which we adapted, some of our choices will not be in our best interest. But revealed preference is the only tool that we have so far to conduct a normative analysis...

  11. Gastrin release: Antrum microdialysis reveals a complex neural control

    DEFF Research Database (Denmark)

    Ericsson, P; Håkanson, R; Rehfeld, Jens F.

    2010-01-01

    We used microdialysis to monitor local gastrin release in response to food, acid blockade and acute vagal excitation. For the first time, gastrin release has been monitored continuously in intact conscious rats in a physiologically relevant experimental setting in a fashion that minimizes...... in serum regardless of the prandial state. The rats were conscious during microdialysis except when subjected to electrical vagal stimulation. Acid blockade (omeprazole treatment of freely fed rats for 4 days), or bilateral sectioning of the abdominal vagal trunks (fasted, 3 days post-op.), raised...... the gastrin concentration in blood as well as microdialysate. The high gastrin concentration following omeprazole treatment was not affected by vagotomy. Vagal excitation stimulated the G cells: electrical vagal stimulation and pylorus ligation (fasted rats) raised the gastrin concentration transiently...

  12. Gastrin release: Antrum microdialysis reveals a complex neural control

    DEFF Research Database (Denmark)

    Ericsson, P; Håkanson, R; Rehfeld, Jens F.

    2010-01-01

    in both serum and microdialysate. Food intake induced a 2- to 3-fold increase in serum gastrin, while gastrin in antral microdialysate increased 10- to 15-fold. In unilaterally vagotomized rats (fasted, 3 days post-op.), food evoked a prompt peak gastrin release followed by a gradual decline on the intact......We used microdialysis to monitor local gastrin release in response to food, acid blockade and acute vagal excitation. For the first time, gastrin release has been monitored continuously in intact conscious rats in a physiologically relevant experimental setting in a fashion that minimizes...... in serum regardless of the prandial state. The rats were conscious during microdialysis except when subjected to electrical vagal stimulation. Acid blockade (omeprazole treatment of freely fed rats for 4 days), or bilateral sectioning of the abdominal vagal trunks (fasted, 3 days post-op.), raised...

  13. Study Reveals Brain Biology behind Self-Control

    Science.gov (United States)

    Sparks, Sarah D.

    2011-01-01

    A new neuroscience twist on a classic psychology study offers some clues to what makes one student able to buckle down for hours of homework before a test while his classmates party. The study published in the September 2011 edition of "Proceedings of the National Academy of Science," suggests environmental cues may "hijack" the brain's mechanisms…

  14. Network analysis reveals multiscale controls on streamwater chemistry

    Science.gov (United States)

    Kevin J. McGuire; Christian E. Torgersen; Gene E. Likens; Donald C. Buso; Winsor H. Lowe; Scott W. Bailey

    2014-01-01

    By coupling synoptic data from a basin-wide assessment of streamwater chemistry with network-based geostatistical analysis, we show that spatial processes differentially affect biogeochemical condition and pattern across a headwater stream network. We analyzed a high-resolution dataset consisting of 664 water samples collected every 100 m throughout 32 tributaries in...

  15. Transparency masters for mathematics revealed

    CERN Document Server

    Berman, Elizabeth

    1980-01-01

    Transparency Masters for Mathematics Revealed focuses on master diagrams that can be used for transparencies for an overhead projector or duplicator masters for worksheets. The book offers information on a compilation of master diagrams prepared by John R. Stafford, Jr., audiovisual supervisor at the University of Missouri at Kansas City. Some of the transparencies are designed to be shown horizontally. The initial three masters are number lines and grids that can be used in a mathematics course, while the others are adaptations of text figures which are slightly altered in some instances. The

  16. Communication Games Reveal Preparation Contextuality

    Science.gov (United States)

    Hameedi, Alley; Tavakoli, Armin; Marques, Breno; Bourennane, Mohamed

    2017-12-01

    A communication game consists of distributed parties attempting to jointly complete a task with restricted communication. Such games are useful tools for studying limitations of physical theories. A theory exhibits preparation contextuality whenever its predictions cannot be explained by a preparation noncontextual model. Here, we show that communication games performed in operational theories reveal the preparation contextuality of that theory. For statistics obtained in a particular family of communication games, we show a direct correspondence with correlations in spacelike separated events obeying the no-signaling principle. Using this, we prove that all mixed quantum states of any finite dimension are preparation contextual. We report on an experimental realization of a communication game involving three-level quantum systems from which we observe a strong violation of the constraints of preparation noncontextuality.

  17. The chemistry of plutonium revealed

    International Nuclear Information System (INIS)

    Connick, R.E.

    1990-01-01

    In 1941 one goal of the Manhattan Project was to unravel the chemistry of the synthetic element plutonium as rapidly as possible. Important insights were obtained from tracer experiments, but the full complexity of plutonium chemistry was not revealed until macroscopic amounts (milligrams) became available. Because processes for separation from fission products were aqueous solution based, such solution chemistry was emphasized, particularly precipitation and oxidation-reduction behavior. The latter turned out to be unusually intricate when it was discovered that two more oxidation states existed in aqueous solution than had previously been suspected. Further, it was found that an equilibrium was rapidly established among the four aqueous oxidation states while at the same time any three were not in equilibrium. These and other observations made while doing a crash study of a previously unknown element will be reported

  18. Plan competitions reveal entrepreneurial talent

    Energy Technology Data Exchange (ETDEWEB)

    Madison, Alison L.

    2011-05-15

    Monthly economic diversity column for Tri-City Herald business section. Excerpt below: There’s something to be said for gaining valuable real-world experience in a structured, nurturing environment. Take for instance learning to scuba dive in the comfort of my resort pool rather than immediately hanging out with sharks while I figure out little things like oxygen tanks and avoiding underwater panic attacks. Likewise, graduate students are getting some excellent, supportive real-world training through university business plan competitions. These competitions are places where smart minds, new technologies, months of preparation and coaching, and some healthy pre-presentation jitters collide to reveal not only solid new business ideas, but also some promising entrepreneurial talent. In fact, professionals from around our region descend upon college campuses every spring to judge these events, which help to bridge the gap between academics and the real technology and business-driven economy.

  19. Transcriptome classification reveals molecular subtypes in psoriasis

    Directory of Open Access Journals (Sweden)

    Ainali Chrysanthi

    2012-09-01

    Full Text Available Abstract Background Psoriasis is an immune-mediated disease characterised by chronically elevated pro-inflammatory cytokine levels, leading to aberrant keratinocyte proliferation and differentiation. Although certain clinical phenotypes, such as plaque psoriasis, are well defined, it is currently unclear whether there are molecular subtypes that might impact on prognosis or treatment outcomes. Results We present a pipeline for patient stratification through a comprehensive analysis of gene expression in paired lesional and non-lesional psoriatic tissue samples, compared with controls, to establish differences in RNA expression patterns across all tissue types. Ensembles of decision tree predictors were employed to cluster psoriatic samples on the basis of gene expression patterns and reveal gene expression signatures that best discriminate molecular disease subtypes. This multi-stage procedure was applied to several published psoriasis studies and a comparison of gene expression patterns across datasets was performed. Conclusion Overall, classification of psoriasis gene expression patterns revealed distinct molecular sub-groups within the clinical phenotype of plaque psoriasis. Enrichment for TGFb and ErbB signaling pathways, noted in one of the two psoriasis subgroups, suggested that this group may be more amenable to therapies targeting these pathways. Our study highlights the potential biological relevance of using ensemble decision tree predictors to determine molecular disease subtypes, in what may initially appear to be a homogenous clinical group. The R code used in this paper is available upon request.

  20. Hubble Images Reveal Jupiter's Auroras

    Science.gov (United States)

    1996-01-01

    These images, taken by the Hubble Space Telescope, reveal changes in Jupiter's auroral emissions and how small auroral spots just outside the emission rings are linked to the planet's volcanic moon, Io. The images represent the most sensitive and sharply-detailed views ever taken of Jovian auroras.The top panel pinpoints the effects of emissions from Io, which is about the size of Earth's moon. The black-and-white image on the left, taken in visible light, shows how Io and Jupiter are linked by an invisible electrical current of charged particles called a 'flux tube.' The particles - ejected from Io (the bright spot on Jupiter's right) by volcanic eruptions - flow along Jupiter's magnetic field lines, which thread through Io, to the planet's north and south magnetic poles. This image also shows the belts of clouds surrounding Jupiter as well as the Great Red Spot.The black-and-white image on the right, taken in ultraviolet light about 15 minutes later, shows Jupiter's auroral emissions at the north and south poles. Just outside these emissions are the auroral spots. Called 'footprints,' the spots are created when the particles in Io's 'flux tube' reach Jupiter's upper atmosphere and interact with hydrogen gas, making it fluoresce. In this image, Io is not observable because it is faint in the ultraviolet.The two ultraviolet images at the bottom of the picture show how the auroral emissions change in brightness and structure as Jupiter rotates. These false-color images also reveal how the magnetic field is offset from Jupiter's spin axis by 10 to 15 degrees. In the right image, the north auroral emission is rising over the left limb; the south auroral oval is beginning to set. The image on the left, obtained on a different date, shows a full view of the north aurora, with a strong emission inside the main auroral oval.The images were taken by the telescope's Wide Field and Planetary Camera 2 between May 1994 and September 1995.This image and other images and data

  1. Focus groups reveal consumer ambivalence.

    Science.gov (United States)

    1983-01-01

    According to qualitative research, Salvadoreans are ambivalent about the use of contraceptives. Since complete responsibility for management of the CSM project was accepted by the Association Demografica Salvadorena (ADS), the agency which operates the contraceptive social marketing project in El Salvador, in November 1980, the need for decisions in such areas as product price increases, introduction of new condom brands, promotion of the vaginal foaming tablet, and assessment of product sales performance had arisen. The ICSMP funded market research, completed during 1983, was intended to provide the data on which such decisions by ADS could be based. The qualitative research involved 8 focus groups, comprised of men and women, aged 18-45, contraceptive users and nonusers, from the middle and lower socioeconomic strata of the city of San Salvador and other suburban areas. In each group a moderator led discussion of family planning and probed respondents for specific attitudes, knowledge, and behavior regarding the use of contraceptives. To assess attitudes at a more emotional level, moderators asked respondents to "draw" their ideas on certain issues. A marked discrepancy was revealed between respondents' intellectual responses to the issues raised in group discussion, as opposed to their feelings expressed in the drawings. Intellectually, participants responded very positively to family planning practice, but when they were asked to draw their perceptions, ambivalent feelings emerged. Drawings of both the user and the nonuser convey primarily negative aspects for either choice. The user is tense and moody toward her children; the nonuser loses her attractiveness and "dies." Figures also show drawings of some of the attitudes of single and married male participants. 1 drawing shows an incomplete and a complete circle, symbolizing a sterilized man (incomplete) and a nonsterilized man (complete). Another picture depicts a chained man who has lost his freedom

  2. Revealing conceptual understanding of international business

    NARCIS (Netherlands)

    Sue Ashley; Dr. Harmen Schaap; Prof.Dr. Elly de Bruijn

    2017-01-01

    This study aims to identify an adequate approach for revealing conceptual understanding in higher professional education. Revealing students’ conceptual understanding is an important step towards developing effective curricula, assessment and aligned teaching strategies to enhance conceptual

  3. Puerto Rico Revealed Preference Survey Data 2004

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Revealed preference models provide insights into recreational angler behavior and the economic value of recreational fishing trips. Revealed preference data is...

  4. Feather corticosterone reveals developmental stress in seabirds.

    Science.gov (United States)

    Will, Alexis P; Suzuki, Yuya; Elliott, Kyle H; Hatch, Scott A; Watanuki, Yutaka; Kitaysky, Alexander S

    2014-07-01

    In nest-bound avian offspring, food shortages typically trigger a release of the stress hormone corticosterone (CORT). Recent studies indicate that CORT is passively deposited in the tissue of growing feathers and thus may provide an integrated measure of stress incurred during development in the nest. The current hypothesis predicts that, assuming a constant rate of feather growth, elevated CORT circulating in the blood corresponds to higher levels of CORT in feather tissue, but experimental evidence for nutritionally stressed chicks is lacking. Here, we examined how food limitation affects feather CORT content in the rhinoceros auklet (Cerorhinca moncerata). We (i) used captive chicks reared on control versus restricted diets, and (ii) applied this technique to free-living chicks with unknown nutritional histories that fledged at three separate colonies. We found that (i) feather growth was not affected by experimentally induced nutritional stress; (ii) captive chicks raised on a restricted diet had higher levels of CORT in their primary feathers; (iii) feather CORT deposition is a sensitive method of detecting nutritional stress; and (iv) free-living fledglings from the colony with poor reproductive performance had higher CORT in their primary feathers. We conclude that feather CORT is a sensitive integrated measure revealing the temporal dynamics of food limitations experienced by rhinoceros auklet nestlings. The use of feather CORT may be a powerful endocrine tool in ecological and evolutionary studies of bird species with similar preferential allocation of limited resources to feather development. © 2014. Published by The Company of Biologists Ltd.

  5. The 'revealed preferences' theory: Assumptions and conjectures

    International Nuclear Information System (INIS)

    Green, C.H.

    1983-01-01

    Being kind of intuitive psychology the 'Revealed-Preferences'- theory based approaches towards determining the acceptable risks are a useful method for the generation of hypotheses. In view of the fact that reliability engineering develops faster than methods for the determination of reliability aims the Revealed-Preferences approach is a necessary preliminary help. Some of the assumptions on which the 'Revealed-Preferences' theory is based will be identified and analysed and afterwards compared with experimentally obtained results. (orig./DG) [de

  6. Revealing Conceptual Understanding of International Business

    Science.gov (United States)

    Ashley, Sue; Schaap, Harmen; de Bruijn, Elly

    2017-01-01

    This study aims to identify an adequate approach for revealing conceptual understanding in higher professional education. Revealing students' conceptual understanding is an important step towards developing effective curricula, assessment and aligned teaching strategies to enhance conceptual understanding in higher education. Essays and concept…

  7. Omics strategies for revealing Yersinia pestis virulence

    Science.gov (United States)

    Yang, Ruifu; Du, Zongmin; Han, Yanping; Zhou, Lei; Song, Yajun; Zhou, Dongsheng; Cui, Yujun

    2012-01-01

    Omics has remarkably changed the way we investigate and understand life. Omics differs from traditional hypothesis-driven research because it is a discovery-driven approach. Mass datasets produced from omics-based studies require experts from different fields to reveal the salient features behind these data. In this review, we summarize omics-driven studies to reveal the virulence features of Yersinia pestis through genomics, trascriptomics, proteomics, interactomics, etc. These studies serve as foundations for further hypothesis-driven research and help us gain insight into Y. pestis pathogenesis. PMID:23248778

  8. Chandra Data Reveal Rapidly Whirling Black Holes

    Science.gov (United States)

    2008-01-01

    A new study using results from NASA's Chandra X-ray Observatory provides one of the best pieces of evidence yet that many supermassive black holes are spinning extremely rapidly. The whirling of these giant black holes drives powerful jets that pump huge amounts of energy into their environment and affects galaxy growth. A team of scientists compared leading theories of jets produced by rotating supermassive black holes with Chandra data. A sampling of nine giant galaxies that exhibit large disturbances in their gaseous atmospheres showed that the central black holes in these galaxies must be spinning at near their maximum rates. People Who Read This Also Read... NASA’s Swift Satellite Catches First Supernova in The Act of Exploding Black Holes Have Simple Feeding Habits Jet Power and Black Hole Assortment Revealed in New Chandra Image Erratic Black Hole Regulates Itself "We think these monster black holes are spinning close to the limit set by Einstein's theory of relativity, which means that they can drag material around them at close to the speed of light," said Rodrigo Nemmen, a visiting graduate student at Penn State University, and lead author of a paper on the new results presented at American Astronomical Society in Austin, Texas. The research reinforces other, less direct methods previously used which have indicated that some stellar and supermassive black holes are spinning rapidly. According to Einstein's theory, a rapidly spinning black hole makes space itself rotate. This effect, coupled with gas spiraling toward the black hole, can produce a rotating, tightly wound vertical tower of magnetic field that flings a large fraction of the inflowing gas away from the vicinity of the black hole in an energetic, high-speed jet. Computer simulations by other authors have suggested that black holes may acquire their rapid spins when galaxies merge, and through the accretion of gas from their surroundings. "Extremely fast spin might be very common for large

  9. Revealed Preference Theory, Rationality, and Neoclassical ...

    African Journals Online (AJOL)

    Revealed Preference Theory (Samuelson 1938) is an attempt to establish economic theory as a genuine empirical science by ridding it of nonempirical psychological concepts. Samuelson's goal was to rid economic theory of the last vestiges of utility analysis. Samuelson structured his theory on a set of preference axioms ...

  10. [Mastitis revealing Churg-Strauss syndrome].

    Science.gov (United States)

    Dannepond, C; Le Fourn, E; de Muret, A; Ouldamer, L; Carmier, D; Machet, L

    2014-01-01

    Churg-Strauss syndrome often involves the skin, and this may sometimes reveal the disease. A 25-year-old woman was referred to a gynaecologist for inflammation of the right breast with breast discharge. Cytological analysis of the liquid showed numerous inflammatory cells, particularly polymorphonuclear eosinophils and neutrophils. Ultrasound examination of the breast was consistent with galactophoritis. CRP was normal, and hypereosinophilia was seen. The patient was subsequently referred to a dermatology unit. Skin examination revealed inflammation of the entire breast, which was painful, warm and erythematous; the border was oedematous with blisters. Necrotic lesions were also present on the thumbs and knees. Skin biopsy of the breast showed a dermal infiltrate with abundant infiltrate of polymorphonuclear eosinophils, including patchy necrosis and intraepidermal vesicles. Histological examination of a biopsy sample from a thumb revealed eosinophilic granuloma and leukocytoclastic vasculitis. The patient was also presenting asthma, pulmonary infiltrates and mononeuropathy at L3, consistent with Churg-Strauss syndrome. Breast involvement in Churg-Strauss syndrome is very rare (only one other case has been reported). This is the first case in which the breast condition revealed the disease. Cutaneous involvement of the breast is, however, also compatible with Wells' cellulitis. The lesions quickly disappeared with 1mg/kg/d oral prednisolone. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  11. Revealed preference tests for collective household behavior

    NARCIS (Netherlands)

    Cherchye, L.J.H.; de Rock, B.; Vermeulen, F.M.P.; Verriest, E.; Molina, J.A.

    2011-01-01

    This chapter contains a state of the art of revealed preference tests for consistency of observed household behavior with Pareto efficiency. These tests are entirely nonparametric, since they do not require any assumptions regarding the parametric form of individual preferences or the intrahousehold

  12. Reveal quantum correlation in complementary bases

    OpenAIRE

    Shengjun Wu; Zhihao Ma; Zhihua Chen; Sixia Yu

    2014-01-01

    An essential feature of genuine quantum correlation is the simultaneous existence of correlation in complementary bases. We reveal this feature of quantum correlation by defining measures based on invariance under a basis change. For a bipartite quantum state, the classical correlation is the maximal correlation present in a certain optimum basis, while the quantum correlation is characterized as a series of residual correlations in the mutually unbiased bases. Compared with other approaches ...

  13. Mediastinal Mature Teratoma Revealed by Empyema

    Directory of Open Access Journals (Sweden)

    Mohammed Raoufi

    2016-01-01

    Full Text Available Teratomas are germ cell tumors, manifested with a great variety of clinical features; the most common extragonadal site is the anterior mediastinum. In this case, we report the patient with a large mature mediastinal teratoma with several components of ectodermal and endothermal epithelium. A 24-year-old female patient presented with history of persistent chest pain and progressively aggravating dyspnea for the previous 3 months. A chest X-ray showed a large opacity of the entire left hemithorax. Transcutaneous needle aspiration revealed a purulent fluid. The tube thoracostomy was introduced and the effusion was evacuated. Some weeks later, patient was seen in emergency for persistent cough and lateral chest pain. CT scan revealed a mass of the left hemithorax. The mass showed heterogeneous density, without compressing mediastinum great vessels and left hilar structures. Lipase value was elevated in needle aspiration. The patient underwent a total resection of the mediastinum mass via a left posterolateral thoracotomy. Microscopy revealed a mature teratoma with cystic structures. The patient subsequently made a full recovery. This case provide benign mediastinal teratoma with total atelectasis of left lung and elevated lipase value in needle transcutaneous aspiration; this event is explained by pancreatic component in the cystic tumor. Total removal of the tumor is adequate treatment for this type of teratoma and the prognosis is excellent.

  14. Gaussian graphical modeling reveals specific lipid correlations in glioblastoma cells

    Science.gov (United States)

    Mueller, Nikola S.; Krumsiek, Jan; Theis, Fabian J.; Böhm, Christian; Meyer-Bäse, Anke

    2011-06-01

    Advances in high-throughput measurements of biological specimens necessitate the development of biologically driven computational techniques. To understand the molecular level of many human diseases, such as cancer, lipid quantifications have been shown to offer an excellent opportunity to reveal disease-specific regulations. The data analysis of the cell lipidome, however, remains a challenging task and cannot be accomplished solely based on intuitive reasoning. We have developed a method to identify a lipid correlation network which is entirely disease-specific. A powerful method to correlate experimentally measured lipid levels across the various samples is a Gaussian Graphical Model (GGM), which is based on partial correlation coefficients. In contrast to regular Pearson correlations, partial correlations aim to identify only direct correlations while eliminating indirect associations. Conventional GGM calculations on the entire dataset can, however, not provide information on whether a correlation is truly disease-specific with respect to the disease samples and not a correlation of control samples. Thus, we implemented a novel differential GGM approach unraveling only the disease-specific correlations, and applied it to the lipidome of immortal Glioblastoma tumor cells. A large set of lipid species were measured by mass spectrometry in order to evaluate lipid remodeling as a result to a combination of perturbation of cells inducing programmed cell death, while the other perturbations served solely as biological controls. With the differential GGM, we were able to reveal Glioblastoma-specific lipid correlations to advance biomedical research on novel gene therapies.

  15. Midface swelling reveals nasofrontal dermal sinus

    International Nuclear Information System (INIS)

    Houneida, Zaghouani Ben Alaya; Manel, Limeme; Latifa, Harzallah; Habib, Amara; Dejla, Bakir; Chekib, Kraiem

    2012-01-01

    Nasofrontal dermal sinuses are very rare and generally occur in children. This congenital malformation can be revealed by midface swelling, which can be complicated by local infection or neuromeningitis. Such complications make the dermal sinus a life-threatening disease. Two cases of nasofrontal dermal sinuses are reported in this work. The first case is an 11-month-old girl who presented with left orbitonasal soft tissue swelling accompanied by inflammation. Physical examination found fever, left orbitonasal thickening, and a puncture hole letting out pus. Computed tomography revealed microabscesses located at the left orbitonasal soft tissues, a frontal bone defect, and an intracranial cyst. Magnetic resonance imaging showed the transosseous tract between the glabella and the brain and affirmed the epidermoid nature of the intracranial cyst. The second case is a 7-year-old girl who presented with a nasofrontal non-progressive mass that intermittently secreted a yellow liquid through an external orifice located at the glabella. MRI revealed a cystic mass located in the deep layer of the glabellar skin related to an epidermoid cyst with a nasofrontal dermal sinus tract. In both cases, surgical excision was performed, and pathological confirmation was made for the diagnoses of dermal sinuses. The postoperative course was favorable. Through these cases, the authors stress the role of imaging methods in confirming the diagnosis and looking for associated cysts (dermoid and epidermoid) to improve recognition of this rare disease. Knowledge of the typical clinical presentations, imaging manifestations, and most common sites of occurrence of this malformation are needed to formulate a differential diagnosis.

  16. Structures of Astromaterials Revealed by EBSD

    Science.gov (United States)

    Zolensky, M.

    2018-01-01

    Groups at the Johnson Space Center and the University of Tokyo have been using electron back-scattered diffraction (EBSD) to reveal the crystal structures of extraterrestrial minerals for many years. Even though we also routinely use transmission electron microscopy, synchrotron X-ray diffraction (SXRD), and conventional electron diffraction, we find that EBSD is the most powerful technique for crystal structure elucidation in many instances. In this talk I describe a few of the cases where we have found EBSD to provide crucial, unique information. See attachment.

  17. [Encopresis revealing myotonic dystrophy in 2 children].

    Science.gov (United States)

    Avez-Couturier, J; Michaud, L; Cuisset, J-M; Lamblin, M-D; Dolhem, P; Turck, D; Vallée, L; Gottrand, F

    2009-05-01

    Gastrointestinal symptoms are very frequent in myotonic dystrophy but largely unrecognized. They can be the revealing factors of the disease. We report 2 cases of 10 and 17-year-old children with persistent encopresis starting at the age of 3 and 5 years in spite of laxative treatment. Neurological examination and anorectal manometry provided the diagnosis of myotonic dystrophy. Procainamide treatment was introduced and the digestive symptoms improved. Any child with encopresis should have complete evaluation to rule out the diagnosis of myotonic dystrophy and physicians should look for upper and/or lower gastrointestinal symptoms in every patient with myotonic dystrophy.

  18. [Severe pulmonary embolism revealed by status epilepticus].

    Science.gov (United States)

    Allou, N; Coolen-Allou, N; Delmas, B; Cordier, C; Allyn, J

    2016-12-01

    High-risk pulmonary embolism (PE) is associated with high mortality rate (>50%). In some cases, diagnosis of PE remains a challenge with atypical presentations like in this case report with a PE revealed by status epilepticus. We report the case of a 40-year-old man without prior disease, hospitalized in ICU for status epilepticus. All paraclinical examinations at admission did not show any significant abnormalities (laboratory tests, cardiologic and neurological investigations). On day 1, he presented a sudden circulatory collapse and echocardiography showed right intra-auricular thrombus. He was treated by thrombolysis and arteriovenous extracorporeal membrane oxygenation. After stabilization, computed tomography showed severe bilateral PE. He developed multi-organ failure and died 4days after admission. Pulmonary embolism revealed by status epilepticus has rarely been reported and is associated with poor prognosis. Physicians should be aware and think of the possibility of PE in patients with status epilepticus without any history or risk factors of seizure and normal neurological investigations. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. [Localized purpura revealing vascular prosthetic graft infection].

    Science.gov (United States)

    Boureau, A S; Lescalie, F; Cassagnau, E; Clairand, R; Connault, J

    2013-07-01

    Prosthetic graft infection after vascular reconstruction is a rare but serious complication. We report a case of infection occurring late after implantation of an iliofemoral prosthetic vascular graft. The Staphylococcus aureus infection was revealed by vascular purpura localized on the right leg 7 years after implantation of a vascular prosthesis. This case illustrates an uncommonly late clinical manifestation presenting as an acute infection 7 years after the primary operation. In this situation, the presentation differs from early infection, which generally occurs within the first four postoperative months. Diagnosis and treatment remain a difficult challenge because prosthetic graft infection is a potentially life-threatening complication. Morbidity and mortality rates are high. Here we detail specific aspects of the clinical and radiological presentation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  20. Chain networking revealed by molecular dynamics simulation

    Science.gov (United States)

    Zheng, Yexin; Tsige, Mesfin; Wang, Shi-Qing

    Based on Kremer-Grest model for entangled polymer melts, we demonstrate how the response of a polymer glass depends critically on the chain length. After quenching two melts of very different chain lengths (350 beads per chain and 30 beads per chain) into deeply glassy states, we subject them to uniaxial extension. Our MD simulations show that the glass of long chains undergoes stable necking after yielding whereas the system of short chains is unable to neck and breaks up after strain localization. During ductile extension of the polymer glass made of long chain significant chain tension builds up in the load-bearing strands (LBSs). Further analysis is expected to reveal evidence of activation of the primary structure during post-yield extension. These results lend support to the recent molecular model 1 and are the simulations to demonstrate the role of chain networking. This work is supported, in part, by a NSF Grant (DMR-EAGER-1444859)

  1. Social patterns revealed through random matrix theory

    Science.gov (United States)

    Sarkar, Camellia; Jalan, Sarika

    2014-11-01

    Despite the tremendous advancements in the field of network theory, very few studies have taken weights in the interactions into consideration that emerge naturally in all real-world systems. Using random matrix analysis of a weighted social network, we demonstrate the profound impact of weights in interactions on emerging structural properties. The analysis reveals that randomness existing in particular time frame affects the decisions of individuals rendering them more freedom of choice in situations of financial security. While the structural organization of networks remains the same throughout all datasets, random matrix theory provides insight into the interaction pattern of individuals of the society in situations of crisis. It has also been contemplated that individual accountability in terms of weighted interactions remains as a key to success unless segregation of tasks comes into play.

  2. Neutron Imaging Reveals Internal Plant Hydraulic Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Warren, Jeffrey [ORNL; Bilheux, Hassina Z [ORNL; Kang, Misun [ORNL; Voisin, Sophie [ORNL; Cheng, Chu-Lin [ORNL; Horita, Jusuke [ORNL; Perfect, Edmund [ORNL

    2013-01-01

    Many terrestrial ecosystem processes are constrained by water availability and transport within the soil. Knowledge of plant water fluxes is thus critical for assessing mechanistic processes linked to biogeochemical cycles, yet resolution of root structure and xylem water transport dynamics has been a particularly daunting task for the ecologist. Through neutron imaging, we demonstrate the ability to non-invasively monitor individual root functionality and water fluxes within Zea mays L. (maize) and Panicum virgatum L. (switchgrass) seedlings growing in a sandy medium. Root structure and growth were readily imaged by neutron radiography and neutron computed tomography. Seedlings were irrigated with water or deuterium oxide and imaged through time as a growth lamp was cycled on to alter leaf demand for water. Sub-millimeter scale resolution reveals timing and magnitudes of root water uptake, redistribution within the roots, and root-shoot hydraulic linkages, relationships not well characterized by other techniques.

  3. Revealing effective classifiers through network comparison

    Science.gov (United States)

    Gallos, Lazaros K.; Fefferman, Nina H.

    2014-11-01

    The ability to compare complex systems can provide new insight into the fundamental nature of the processes captured, in ways that are otherwise inaccessible to observation. Here, we introduce the n-tangle method to directly compare two networks for structural similarity, based on the distribution of edge density in network subgraphs. We demonstrate that this method can efficiently introduce comparative analysis into network science and opens the road for many new applications. For example, we show how the construction of a “phylogenetic tree” across animal taxa according to their social structure can reveal commonalities in the behavioral ecology of the populations, or how students create similar networks according to the University size. Our method can be expanded to study many additional properties, such as network classification, changes during time evolution, convergence of growth models, and detection of structural changes during damage.

  4. Hidden acoustic information revealed by intentional nonlinearity

    Science.gov (United States)

    Dowling, David R.

    2017-11-01

    Acoustic waves are omnipresent in modern life and are well described by the linearized equations of fluid dynamics. Once generated, acoustic waves carry and collect information about their source and the environment through which they propagate, respectively, and this information may be retrieved by analyzing recordings of these waves. Because of this, acoustics is the primary means for observation, surveillance, reconnaissance, and remote sensing in otherwise opaque environments, such as the Earth's oceans and crust, and the interior of the human body. For such information-retrieval tasks, acoustic fields are nearly always interrogated within their recorded frequency range or bandwidth. However, this frequency-range restriction is not general; acoustic fields may also carry (hidden) information at frequencies outside their bandwidth. Although such a claim may seem counter intuitive, hidden acoustic-field information can be revealed by re-introducing a marquee trait of fluid dynamics: nonlinearity. In particular, an intentional quadratic nonlinearity - a form of intra-signal heterodyning - can be used to obtain acoustic field information at frequencies outside a recorded acoustic field's bandwidth. This quadratic nonlinearity enables a variety of acoustic remote sensing applications that were long thought to be impossible. In particular, it allows the detrimental effects of sparse recordings and random scattering to be suppressed when the original acoustic field has sufficient bandwidth. In this presentation, the topic is developed heuristically, with a just brief exposition of the relevant mathematics. Hidden acoustic field information is then revealed from simulated and measured acoustic fields in simple and complicated acoustic environments involving frequencies from a few Hertz to more than 100 kHz, and propagation distances from tens of centimeters to hundreds of kilometers. Sponsored by ONR, NAVSEA, and NSF.

  5. Ceres Revealed in a Grain of Salt

    Science.gov (United States)

    Zolensky, M. E.; Bodnar, R. J.; Fries, M.; Chan, Q. H.-S.; Kebukawa, Y.; Mikouchi, T.; Hagiya, K.; Komatsu, M.; Ohsumi, K.; Steele, A.

    2016-01-01

    Introduction: Zag and Monahans (1998) are H chondrite regolith breccias containing 4.5 giga-year-old halite crystals which contain abundant inclusions of aqueous fluids, solids and organics. These all originated on a cryo-volcanically-active C class asteroid, probably 1 Ceres; the halite was transported to the regolith of the H chondrite parent asteroid, potentially 6 Hebe. Detailed analysis of these solids will thus potentially reveal the mineralogy of Ceres. Mineralogy of solids in the Monahans Halite Solid grains are present in the halites, which were entrained within the mother brines during eruption, including material from the interior and surface of the erupting body. The solids include abundant, widely variable organics that could not have been significantly heated (which would have resulted in the loss of fluids from the halite). Our analyses by Raman microprobe, SEM/EDX, synchrotron X-ray diffraction, UPLC-FD/QToF-MS, C-XANES and TEM reveal that these trapped grains include macromolecular carbon (MMC) similar in structure to CV3 chondrite matrix carbon, aliphatic carbon compounds, olivine (Fo99-59), high- and low-Ca pyroxene, feldspars, phyllosilicates, magnetite, sulfides, metal, lepidocrocite, carbonates, diamond, apatite and zeolites. Conclusions: The halite in Monahans and Zag derive from a water and carbon-rich object that was cryo-volcanically active in the early solar system, probably Ceres. The Dawn spacecraft found that Ceres includes C chondrite materials. Our samples include both protolith and aqueously-altered samples of the body, permitting understanding of alteration conditions. Whatever the halite parent body, it was rich in a wide variety of organics and warm, liquid water at the solar system's dawn.

  6. Controllable circuit

    DEFF Research Database (Denmark)

    2010-01-01

    A switch-mode power circuit comprises a controllable element and a control unit. The controllable element is configured to control a current in response to a control signal supplied to the controllable element. The control unit is connected to the controllable element and provides the control...

  7. Multilocus analysis reveals three candidate genes for Chinese migraine susceptibility.

    Science.gov (United States)

    An, X-K; Fang, J; Yu, Z-Z; Lin, Q; Lu, C-X; Qu, H-L; Ma, Q-L

    2017-08-01

    Several genome-wide association studies (GWASs) in Caucasian populations have identified 12 loci that are significantly associated with migraine. More evidence suggests that serotonin receptors are also involved in migraine pathophysiology. In the present study, a case-control study was conducted in a cohort of 581 migraine cases and 533 ethnically matched controls among a Chinese population. Eighteen polymorphisms from serotonin receptors and GWASs were selected, and genotyping was performed using a Sequenom MALDI-TOF mass spectrometry iPLEX platform. The genotypic and allelic distributions of MEF2D rs2274316 and ASTN2 rs6478241 were significantly different between migraine patients and controls. Univariate and multivariate analysis revealed significant associations of polymorphisms in the MEF2D and ASTN2 genes with migraine susceptibility. MEF2D, PRDM16 and ASTN2 were also found to be associated with migraine without aura (MO) and migraine with family history. And, MEF2D and ASTN2 also served as genetic risk factors for the migraine without family history. The generalized multifactor dimensionality reduction analysis identified that MEF2D and HTR2E constituted the two-factor interaction model. Our study suggests that the MEF2D, PRDM16 and ASTN2 genes from GWAS are associated with migraine susceptibility, especially MO, among Chinese patients. It appears that there is no association with serotonin receptor related genes. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Dislocation Interactions in Olivine Revealed by HR-EBSD

    Science.gov (United States)

    Wallis, David; Hansen, Lars N.; Britton, T. Ben; Wilkinson, Angus J.

    2017-10-01

    Interactions between dislocations potentially provide a control on strain rates produced by dislocation motion during creep of rocks at high temperatures. However, it has been difficult to establish the dominant types of interactions and their influence on the rheological properties of creeping rocks due to a lack of suitable observational techniques. We apply high-angular resolution electron backscatter diffraction to map geometrically necessary dislocation (GND) density, elastic strain, and residual stress in experimentally deformed single crystals of olivine. Short-range interactions are revealed by cross correlation of GND density maps. Spatial correlations between dislocation types indicate that noncollinear interactions may impede motion of proximal dislocations at temperatures of 1000°C and 1200°C. Long-range interactions are revealed by autocorrelation of GND density maps. These analyses reveal periodic variations in GND density and sign, with characteristic length scales on the order of 1-10 μm. These structures are spatially associated with variations in elastic strain and residual stress on the order of 10-3 and 100 MPa, respectively. Therefore, short-range interactions generate local accumulations of dislocations, leading to heterogeneous internal stress fields that influence dislocation motion over longer length scales. The impacts of these short- and/or long-range interactions on dislocation velocities may therefore influence the strain rate of the bulk material and are an important consideration for future models of dislocation-mediated deformation mechanisms in olivine. Establishing the types and impacts of dislocation interactions that occur across a range of laboratory and natural deformation conditions will help to establish the reliability of extrapolating laboratory-derived flow laws to real Earth conditions.

  9. Supply Chain Management In Construction Revealed

    Directory of Open Access Journals (Sweden)

    Dr. Ghaith Al-Werikat

    2017-03-01

    Full Text Available The construction supply chain plays a major role in the construction market competition. Construction supply chain management assists enterprises by helping to improve competitiveness increase profits and have more control over the different factors and variables within the project. This paper discusses the construction supply chain characteristics challenges and problems supply chains encounter and the benefits of an integrated supply chain in the construction sector.

  10. Supply Chain Management In Construction Revealed

    OpenAIRE

    Dr. Ghaith Al-Werikat

    2017-01-01

    The construction supply chain plays a major role in the construction market competition. Construction supply chain management assists enterprises by helping to improve competitiveness increase profits and have more control over the different factors and variables within the project. This paper discusses the construction supply chain characteristics challenges and problems supply chains encounter and the benefits of an integrated supply chain in the construction sector.

  11. Enhanced limonene production in cyanobacteria reveals photosynthesis limitations.

    Science.gov (United States)

    Wang, Xin; Liu, Wei; Xin, Changpeng; Zheng, Yi; Cheng, Yanbing; Sun, Su; Li, Runze; Zhu, Xin-Guang; Dai, Susie Y; Rentzepis, Peter M; Yuan, Joshua S

    2016-12-13

    Terpenes are the major secondary metabolites produced by plants, and have diverse industrial applications as pharmaceuticals, fragrance, solvents, and biofuels. Cyanobacteria are equipped with efficient carbon fixation mechanism, and are ideal cell factories to produce various fuel and chemical products. Past efforts to produce terpenes in photosynthetic organisms have gained only limited success. Here we engineered the cyanobacterium Synechococcus elongatus PCC 7942 to efficiently produce limonene through modeling guided study. Computational modeling of limonene flux in response to photosynthetic output has revealed the downstream terpene synthase as a key metabolic flux-controlling node in the MEP (2-C-methyl-d-erythritol 4-phosphate) pathway-derived terpene biosynthesis. By enhancing the downstream limonene carbon sink, we achieved over 100-fold increase in limonene productivity, in contrast to the marginal increase achieved through stepwise metabolic engineering. The establishment of a strong limonene flux revealed potential synergy between photosynthate output and terpene biosynthesis, leading to enhanced carbon flux into the MEP pathway. Moreover, we show that enhanced limonene flux would lead to NADPH accumulation, and slow down photosynthesis electron flow. Fine-tuning ATP/NADPH toward terpene biosynthesis could be a key parameter to adapt photosynthesis to support biofuel/bioproduct production in cyanobacteria.

  12. [Thoracic aortic dissection revealed by systemic cholesterol embolism].

    Science.gov (United States)

    Braem, L; Paule, P; Héno, P; Morand, J J; Mafart, B; La Folie, T; Varlet, P; Mioulet, D; Fourcade, L

    2006-10-01

    Systemic cholesterol embolism is a rare complication of atherosclerosis, and has various presentations. Arterial catheterisms are a common cause. However, the association with an aortic dissection has been exceptionally reported. We report the observation of a 70 year-old man, with coronary artery disease, hypertension, diabetes and dyslipidemia. Six months before hospitalization, a coronary angioplasty was performed due to recurrent angina. The association of purpuric lesions on the feet, with acute renal failure confirmed cholesterol embolism syndrome. Transoesophageal echocardiography showed a dissection of the descending thoracic aorta associated with complex atheroma. The evolution was marked by the pulpar necrosis of a toe and by a worsening of the renal failure, requiring definitive hemodialysis. Further echographic control highlighted the rupture of the intimal veil of the dissection. Cholesterol embolism syndrome may reveal an aortic dissection in patients without thoracic symptoms. In such cases, transoesophageal echocardiography is a useful and non-invasive examination.

  13. Control rod control device

    International Nuclear Information System (INIS)

    Seiji, Takehiko; Obara, Kohei; Yanagihashi, Kazumi

    1998-01-01

    The present invention provides a device suitable for switching of electric motors for driving each of control rods in a nuclear reactor. Namely, in a control rod controlling device, a plurality of previously allotted electric motors connected in parallel as groups, and electric motors of any selected group are driven. In this case, a voltage of not driving predetermined selected electric motors is at first applied. In this state an electric current supplied to the circuit of predetermined electric motors is detected. Whether integration or failure of a power source and the circuit of the predetermined electric motors are normal or not is judged by the detected electric current supplied. After they are judged normal, the electric motors are driven by a regular voltage. With such procedures, whether the selected circuit is normal or not can be accurately confirmed previously. Since the electric motors are not driven just at the selected time, the control rods are not operated erroneously. (I.S.)

  14. ERYTHEMA NODOSUM REVEALING ACUTE MYELOID LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Chebbi Wafa

    2013-07-01

    Full Text Available Introduction: Erythema nodosum (EN is the most common type of panniculitis. It may be idiopathic or secondary to various etiologies. However, the occurrence of erythema nodosum in malignant hemopathy had rarely been reported. Case report: A 42 year-old woman presented with a four week history of recurrent multiple painful erythematous nodules developed on the lower limbs associated with arthralgia of the ankles and fever. The clinical features of skin lesions with contusiform color evolution allowed establishing the diagnosis of EN. No underlying cause was found. The skin lesions were improved with non-steroidal anti-inflammatory drugs and colchicine. Three months later, the patient consulted for recurrence of EN associated with fever, inflammatory polyarthralgia and hepatosplenomegaly. The peripheral blood count revealed pancytopenia. A bone marrow examination confirmed the diagnosis of acute myeloid leukemia type 2. Initiation of chemotherapy was followed by the complete disappearance of skin lesions of EN. Conclusion: Paraneoplastic erythema nodosum is a rare entity. In the literature, a few cases of association with leukemia have been reported. Exploration for solid neoplasms or hemopathy in case of recurrent EN or resistance to conventional treatment should be systematic

  15. Revealing the values behind convenience food consumption.

    Science.gov (United States)

    Botonaki, Anna; Mattas, Konstadinos

    2010-12-01

    The increasing importance of convenience in consumer food choices has attracted researchers' interest. In the effort to understand how convenience affects consumers' food preferences, values are believed to play an important role. The present study attempts to examine the way personal values suggested by Schwartz (1992) are associated with behaviour and attitudes regarding convenience food. A number of constructs describing food related attitudes and behaviours were developed and their relationship with personal values was analyzed following the methodology proposed by Brunsø, Scholderer, and Grunert (2004). Data were collected through a questionnaire survey from a random sample of consumers in Thessaloniki city, Greece. The results reveal that convenience food consumption and convenience orientation in the food domain are mainly connected with values that motivate people to seek new experiences, act independently and enhance their own personal interests, while are in conflict with values of conservation and self-transcendence. The opposite holds for other food related attitudes and behaviours like involvement with cooking and variety in diet. The findings seem to be of particular interest not only for marketers of food products, but also for food policy makers. Copyright © 2010 Elsevier Ltd. All rights reserved.

  16. Revealing source signatures in ambient BTEX concentrations

    International Nuclear Information System (INIS)

    Zalel, Amir; Yuval; Broday, David M.

    2008-01-01

    Management of ambient concentrations of Volatile Organic Compounds (VOCs) is essential for maintaining low ozone levels in urban areas where its formation is under a VOC-limited regime. The significant decrease in traffic-induced VOC emissions in many developed countries resulted in relatively comparable shares of traffic and non-traffic VOC emissions in urban airsheds. A key step for urban air quality management is allocating ambient VOC concentrations to their pertinent sources. This study presents an approach that can aid in identifying sources that contribute to observed BTEX concentrations in areas characterized by low BTEX concentrations, where traditional source apportionment techniques are not useful. Analysis of seasonal and diurnal variations of ambient BTEX concentrations from two monitoring stations located in distinct areas reveal the possibility to identify source categories. Specifically, the varying oxidation rates of airborne BTEX compounds are used to allocate contributions of traffic emissions and evaporative sources to observed BTEX concentrations. - BTEX sources are identified from temporal variations of ambient concentration

  17. VISTA Reveals the Secret of the Unicorn

    Science.gov (United States)

    2010-10-01

    A new infrared image from ESO's VISTA survey telescope reveals an extraordinary landscape of glowing tendrils of gas, dark clouds and young stars within the constellation of Monoceros (the Unicorn). This star-forming region, known as Monoceros R2, is embedded within a huge dark cloud. The region is almost completely obscured by interstellar dust when viewed in visible light, but is spectacular in the infrared. An active stellar nursery lies hidden inside a massive dark cloud rich in molecules and dust in the constellation of Monoceros. Although it appears close in the sky to the more familiar Orion Nebula it is actually almost twice as far from Earth, at a distance of about 2700 light-years. In visible light a grouping of massive hot stars creates a beautiful collection of reflection nebulae where the bluish starlight is scattered from parts of the dark, foggy outer layers of the molecular cloud. However, most of the new-born massive stars remain hidden as the thick interstellar dust strongly absorbs their ultraviolet and visible light. In this gorgeous infrared image taken from ESO's Paranal Observatory in northern Chile, the Visible and Infrared Survey Telescope for Astronomy (VISTA [1], eso0949) penetrates the dark curtain of cosmic dust and reveals in astonishing detail the folds, loops and filaments sculpted from the dusty interstellar matter by intense particle winds and the radiation emitted by hot young stars. "When I first saw this image I just said 'Wow!' I was amazed to see all the dust streamers so clearly around the Monoceros R2 cluster, as well as the jets from highly embedded young stellar objects. There is such a great wealth of exciting detail revealed in these VISTA images," says Jim Emerson, of Queen Mary, University of London and leader of the VISTA consortium. With its huge field of view, large mirror and sensitive camera, VISTA is ideal for obtaining deep, high quality infrared images of large areas of the sky, such as the Monoceros R2 region

  18. On revealing graph cycles via boundary measurements

    International Nuclear Information System (INIS)

    Belishev, M I; Wada, N

    2009-01-01

    This paper deals with boundary value inverse problems on a metric graph, the structure of the graph being assumed unknown. The question under consideration is how to detect from the dynamical and/or spectral inverse data whether the graph contains cycles (is not a tree). For any graph Ω, the dynamical as well as spectral boundary inverse data determine the so-called wave diameter d w : H -1 (Ω) → R defined on functionals supported in the graph. The known fact is that if Ω is a tree then d w ≥ 0 holds and, in this case, the inverse data determine Ω up to isometry. A graph Ω is said to be coordinate if the functions {dist Ω (., γ)} γin∂Ω constitute a coordinate system on Ω. For such graphs, we propose a procedure, which reveals the presence/absence of cycles. The hypothesis is that Ω contains cycles if and only if d w takes negative values. We do not justify this hypothesis in the general case but reduce it to a certain special class of graphs (suns)

  19. Sequence tagging reveals unexpected modifications in toxicoproteomics

    Science.gov (United States)

    Dasari, Surendra; Chambers, Matthew C.; Codreanu, Simona G.; Liebler, Daniel C.; Collins, Ben C.; Pennington, Stephen R.; Gallagher, William M.; Tabb, David L.

    2010-01-01

    Toxicoproteomic samples are rich in posttranslational modifications (PTMs) of proteins. Identifying these modifications via standard database searching can incur significant performance penalties. Here we describe the latest developments in TagRecon, an algorithm that leverages inferred sequence tags to identify modified peptides in toxicoproteomic data sets. TagRecon identifies known modifications more effectively than the MyriMatch database search engine. TagRecon outperformed state of the art software in recognizing unanticipated modifications from LTQ, Orbitrap, and QTOF data sets. We developed user-friendly software for detecting persistent mass shifts from samples. We follow a three-step strategy for detecting unanticipated PTMs in samples. First, we identify the proteins present in the sample with a standard database search. Next, identified proteins are interrogated for unexpected PTMs with a sequence tag-based search. Finally, additional evidence is gathered for the detected mass shifts with a refinement search. Application of this technology on toxicoproteomic data sets revealed unintended cross-reactions between proteins and sample processing reagents. Twenty five proteins in rat liver showed signs of oxidative stress when exposed to potentially toxic drugs. These results demonstrate the value of mining toxicoproteomic data sets for modifications. PMID:21214251

  20. Featured Image: Revealing Hidden Objects with Color

    Science.gov (United States)

    Kohler, Susanna

    2018-02-01

    Stunning color astronomical images can often be the motivation for astronomers to continue slogging through countless data files, calculations, and simulations as we seek to understand the mysteries of the universe. But sometimes the stunning images can, themselves, be the source of scientific discovery. This is the case with the below image of Lynds Dark Nebula 673, located in the Aquila constellation, that was captured with the Mayall 4-meter telescope at Kitt Peak National Observatory by a team of scientists led by Travis Rector (University of Alaska Anchorage). After creating the image with a novel color-composite imaging method that reveals faint H emission (visible in red in both images here), Rector and collaborators identified the presence of a dozen new Herbig-Haro objects small cloud patches that are caused when material is energetically flung out from newly born stars. The image adapted above shows three of the new objects, HH 118789, aligned with two previously known objects, HH 32 and 332 suggesting they are driven by the same source. For more beautiful images and insight into the authors discoveries, check out the article linked below!Full view of Lynds Dark Nebula 673. Click for the larger view this beautiful composite image deserves! [T.A. Rector (University of Alaska Anchorage) and H. Schweiker (WIYN and NOAO/AURA/NSF)]CitationT. A. Rector et al 2018 ApJ 852 13. doi:10.3847/1538-4357/aa9ce1

  1. [Polymyalgia rheumatica revealing a lung cancer].

    Science.gov (United States)

    Cocquempot, K; Defuentes, G; Duron-Martineau, S; Berets, O; Vaylet, F; Margery, J

    2013-01-01

    Polymyalgia rheumatica is an inflammatory condition belonging to the connective tissue diseases, which occurs quite frequently in the elderly. Previously, cases have been reported in association with malignant tumours, in a synchronous fashion or prior to the appearance of the cancer. In these cases, the polymyalgia rheumatica is considered to be a paraneoplastic syndrome. We report the cases of a 63-year-old woman and a 58-year-old man with severe proximal girdle pain associated to a high-level of systemic inflammatory markers and a diagnosis of polymyalgia rheumatica was made. In the face of a lack of ineffectiveness of analgesic and anti-inflammatory treatments, an intensive investigation was undertaken which in both cases revealed an adenocarcinoma of the lung. The rheumatic manifestations responded well to chemotherapy targeting the lung tumour. We present here a review of the literature to give prominence to the diagnostic pitfalls that can occur around paraneoplastic polymyalgia rheumatica. The presence of therapeutic resistance at the onset of treatment and other atypical features may suggest the presence of an occult malignancy. Copyright © 2012 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  2. Human tears reveal insights into corneal neovascularization.

    Science.gov (United States)

    Zakaria, Nadia; Van Grasdorff, Sigi; Wouters, Kristien; Rozema, Jos; Koppen, Carina; Lion, Eva; Cools, Nathalie; Berneman, Zwi; Tassignon, Marie-José

    2012-01-01

    Corneal neovascularization results from the encroachment of blood vessels from the surrounding conjunctiva onto the normally avascular cornea. The aim of this study is to identify factors in human tears that are involved in development and/or maintenance of corneal neovascularization in humans. This could allow development of diagnostic tools for monitoring corneal neovascularization and combination monoclonal antibody therapies for its treatment. In an observational case-control study we enrolled a total of 12 patients with corneal neovascularization and 10 healthy volunteers. Basal tears along with reflex tears from the inferior fornix, superior fornix and using a corneal bath were collected along with blood serum samples. From all patients, ocular surface photographs were taken. Concentrations of the pro-angiogenic cytokines interleukin (IL)-6, IL-8, Vascular Endothelial Growth Factor (VEGF), Monocyte Chemoattractant Protein 1 (MCP-1) and Fas Ligand (FasL) were determined in blood and tear samples using a flow cytometric multiplex assay. Our results show that the concentration of pro-angiogenic cytokines in human tears are significantly higher compared to their concentrations in serum, with highest levels found in basal tears. Interestingly, we could detect a significantly higher concentration of IL- 6, IL-8 and VEGF in localized corneal tears of patients with neovascularized corneas when compared to the control group. This is the first study of its kind demonstrating a significant difference of defined factors in tears from patients with neovascularized corneas as compared to healthy controls. These results provide the basis for future research using animal models to further substantiate the role of these cytokines in the establishment and maintenance of corneal neovascularization.

  3. Robotics for mining control

    Energy Technology Data Exchange (ETDEWEB)

    1986-11-01

    In 1982 surveys of the mining industry revealed no applications of robotics existed and none were planned. This report provides a general overview of automation in the mining industry since this point in time. Roof control electronics, gas monitoring, jumbo drill automation, remote and sensor- controlled continuous miners, automated trolley trucks, roof bolting and screening machines are examples of technology available today. The report concludes with recommendations as to six potential research areas. 25 refs.

  4. Radio Telescopes Reveal Unseen Galactic Cannibalism

    Science.gov (United States)

    2008-06-01

    Radio-telescope images have revealed previously-unseen galactic cannibalism -- a triggering event that leads to feeding frenzies by gigantic black holes at the cores of galaxies. Astronomers have long suspected that the extra-bright cores of spiral galaxies called Seyfert galaxies are powered by supermassive black holes consuming material. However, they could not see how the material is started on its journey toward the black hole. Optical/Radio Comparison Visible-light (left) and radio (right) image of galaxy pair: Radio image shows gas streaming between galaxies. CREDIT: Kuo et al., NRAO/AUI/NSF Click on image for more graphics. One leading theory said that Seyfert galaxies have been disturbed by close encounters with neighboring galaxies, thus stirring up their gas and bringing more of it within the gravitational reach of the black hole. However, when astronomers looked at Seyferts with visible-light telescopes, only a small fraction showed any evidence of such an encounter. Now, new images of hydrogen gas in Seyferts made using the National Science Foundation's Very Large Array (VLA) radio telescope show the majority of them are, in fact, disturbed by ongoing encounters with neighbor galaxies. "The VLA lifted the veil on what's really happening with these galaxies," said Cheng-Yu Kuo, a graduate student at the University of Virginia. "Looking at the gas in these galaxies clearly showed that they are snacking on their neighbors. This is a dramatic contrast with their appearance in visible starlight," he added. The effect of the galactic encounters is to send gas and dust toward the black hole and produce energy as the material ultimately is consumed. Black holes, concentrations of matter so dense that not even light can escape their gravitational pull, reside at the cores of many galaxies. Depending on how rapidly the black hole is eating, the galaxy can show a wide range of energetic activity. Seyfert galaxies have the mildest version of this activity, while

  5. Revealing household characteristics from smart meter data

    International Nuclear Information System (INIS)

    Beckel, Christian; Sadamori, Leyna; Staake, Thorsten; Santini, Silvia

    2014-01-01

    Utilities are currently deploying smart electricity meters in millions of households worldwide to collect fine-grained electricity consumption data. We present an approach to automatically analyzing this data to enable personalized and scalable energy efficiency programs for private households. In particular, we develop and evaluate a system that uses supervised machine learning techniques to automatically estimate specific “characteristics” of a household from its electricity consumption. The characteristics are related to a household's socio-economic status, its dwelling, or its appliance stock. We evaluate our approach by analyzing smart meter data collected from 4232 households in Ireland at a 30-min granularity over a period of 1.5 years. Our analysis shows that revealing characteristics from smart meter data is feasible, as our method achieves an accuracy of more than 70% over all households for many of the characteristics and even exceeds 80% for some of the characteristics. The findings are applicable to all smart metering systems without making changes to the measurement infrastructure. The inferred knowledge paves the way for targeted energy efficiency programs and other services that benefit from improved customer insights. On the basis of these promising results, the paper discusses the potential for utilities as well as policy and privacy implications. - Highlights: • Many household characteristics can be automatically inferred from smart meter data. • We develop a system to infer employment status and number of occupants, for instance. • We evaluate our system analyzing data collected from 4232 households in Ireland. • The insights enable personalized and scalable efficiency campaigns for utilities. • Energy efficiency measures must be complemented by privacy protection

  6. Phase-Specific Vocalizations of Male Mice at the Initial Encounter during the Courtship Sequence.

    Directory of Open Access Journals (Sweden)

    Yui K Matsumoto

    Full Text Available Mice produce ultrasonic vocalizations featuring a variety of syllables. Vocalizations are observed during social interactions. In particular, males produce numerous syllables during courtship. Previous studies have shown that vocalizations change according to sexual behavior, suggesting that males vary their vocalizations depending on the phase of the courtship sequence. To examine this process, we recorded large sets of mouse vocalizations during male-female interactions and acoustically categorized these sounds into 12 vocal types. We found that males emitted predominantly short syllables during the first minute of interaction, more long syllables in the later phases, and mainly harmonic sounds during mounting. These context- and time-dependent changes in vocalization indicate that vocal communication during courtship in mice consists of at least three stages and imply that each vocalization type has a specific role in a phase of the courtship sequence. Our findings suggest that recording for a sufficiently long time and taking the phase of courtship into consideration could provide more insights into the role of vocalization in mouse courtship behavior in future study.

  7. Growth-Phase-Specific Modulation of Cell Morphology and Gene Expression by an Archaeal Histone Protein.

    Science.gov (United States)

    Dulmage, Keely A; Todor, Horia; Schmid, Amy K

    2015-09-08

    In all three domains of life, organisms use nonspecific DNA-binding proteins to compact and organize the genome as well as to regulate transcription on a global scale. Histone is the primary eukaryotic nucleoprotein, and its evolutionary roots can be traced to the archaea. However, not all archaea use this protein as the primary DNA-packaging component, raising questions regarding the role of histones in archaeal chromatin function. Here, quantitative phenotyping, transcriptomic, and proteomic assays were performed on deletion and overexpression mutants of the sole histone protein of the hypersaline-adapted haloarchaeal model organism Halobacterium salinarum. This protein is highly conserved among all sequenced haloarchaeal species and maintains hallmark residues required for eukaryotic histone functions. Surprisingly, despite this conservation at the sequence level, unlike in other archaea or eukaryotes, H. salinarum histone is required to regulate cell shape but is not necessary for survival. Genome-wide expression changes in histone deletion strains were global, significant but subtle in terms of fold change, bidirectional, and growth phase dependent. Mass spectrometric proteomic identification of proteins from chromatin enrichments yielded levels of histone and putative nucleoid-associated proteins similar to those of transcription factors, consistent with an open and transcriptionally active genome. Taken together, these data suggest that histone in H. salinarum plays a minor role in DNA compaction but important roles in growth-phase-dependent gene expression and regulation of cell shape. Histone function in haloarchaea more closely resembles a regulator of gene expression than a chromatin-organizing protein like canonical eukaryotic histone. Histones comprise the major protein component of eukaryotic chromatin and are required for both genome packaging and global regulation of expression. The current paradigm maintains that archaea whose genes encode histone also use these proteins to package DNA. In contrast, here we demonstrate that the sole histone encoded in the genome of the salt-adapted archaeon Halobacterium salinarum is both unessential and unlikely to be involved in DNA compaction despite conservation of residues important for eukaryotic histones. Rather, H. salinarum histone is required for global regulation of gene expression and cell shape. These data are consistent with the hypothesis that H. salinarum histone, strongly conserved across all other known salt-adapted archaea, serves a novel role in gene regulation and cell shape maintenance. Given that archaea possess the ancestral form of eukaryotic histone, this study has important implications for understanding the evolution of histone function. Copyright © 2015 Dulmage et al.

  8. Nongenotoxic p53 activation protects cells against S-phase-specific chemotherapy

    DEFF Research Database (Denmark)

    Kranz, Dominique; Dobbelstein, Matthias

    2006-01-01

    Mutations in the tumor suppressor gene TP53 represent the most frequent genetic difference between tumor cells and normal cells. Here, we have attempted to turn this difference into an advantage for normal cells during therapy. Using the Mdm2 antagonist nutlin-3, we first activated p53 in U2OS an...... a killer to a protector of cells, with the potential to reduce unwanted side effects of chemotherapy....

  9. The proliferative status of intestinal epithelial clonogenic cells: sensitivity to S phase specific cytotoxic agents.

    Science.gov (United States)

    Boarder, T A; Blackett, N M

    1976-11-01

    High concentrations of tritiated thymidine and cytosine arabinoside (Ara-C) have been used to selectively kill cells in the crypts of Lieberkuhn that are synthesizing DNA. The effect of these agents on the number of regenerating microcolonies seen 3 1/2 days after a range of radiation doses indicates that a majority of the clonogenic cells are proliferating rapidly and that the slowly proliferating cells at the base of the crypt do not represent the whole clonogenic population.

  10. Water Pollution Control Industry

    Science.gov (United States)

    Environmental Science and Technology, 1974

    1974-01-01

    A special report on the state of the water pollution control industry reveals that due to forthcoming federal requirements, sales and the backlogs should increase; problems may ensue because of shortages of materials and inflation. Included are reports from various individual companies. (MLB)

  11. Strategy revealing phenotypic differences among synthetic oscillator designs.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2014-09-19

    Considerable progress has been made in identifying and characterizing the component parts of genetic oscillators, which play central roles in all organisms. Nonlinear interaction among components is sufficiently complex that mathematical models are required to elucidate their elusive integrated behavior. Although natural and synthetic oscillators exhibit common architectures, there are numerous differences that are poorly understood. Utilizing synthetic biology to uncover basic principles of simpler circuits is a way to advance understanding of natural circadian clocks and rhythms. Following this strategy, we address the following questions: What are the implications of different architectures and molecular modes of transcriptional control for the phenotypic repertoire of genetic oscillators? Are there designs that are more realizable or robust? We compare synthetic oscillators involving one of three architectures and various combinations of the two modes of transcriptional control using a methodology that provides three innovations: a rigorous definition of phenotype, a procedure for deconstructing complex systems into qualitatively distinct phenotypes, and a graphical representation for illuminating the relationship between genotype, environment, and the qualitatively distinct phenotypes of a system. These methods provide a global perspective on the behavioral repertoire, facilitate comparisons of alternatives, and assist the rational design of synthetic gene circuitry. In particular, the results of their application here reveal distinctive phenotypes for several designs that have been studied experimentally as well as a best design among the alternatives that has yet to be constructed and tested.

  12. Microradiometers Reveal Ocean Health, Climate Change

    Science.gov (United States)

    2013-01-01

    When NASA researcher Stanford Hooker is in the field, he pays close attention to color. For Hooker, being in the field means being at sea. On one such research trip to the frigid waters of the Arctic, with a Coast Guard icebreaker looming nearby and the snow-crusted ice shelf a few feet away, Hooker leaned over the edge of his small boat and lowered a tethered device into the bright turquoise water, a new product devised by a NASA partner and enabled by a promising technology for oceanographers and atmospheric scientists alike. Color is a function of light. Pure water is clear, but the variation in color observed during a visit to the beach or a flight along a coastline depends on the water s depth and the constituents in it, how far down the light penetrates and how it is absorbed and scattered by dissolved and suspended material. Hooker cares about ocean color because of what it can reveal about the health of the ocean, and in turn, the health of our planet. "The main thing we are interested in is the productivity of the water," Hooker says. The seawater contains phytoplankton, microscopic plants, which are the food base for the ocean s ecosystems. Changes in the water s properties, whether due to natural seasonal effects or human influence, can lead to problems for delicate ecosystems such as coral reefs. Ocean color can inform researchers about the quantities and distribution of phytoplankton and other materials, providing clues as to how the world ocean is changing. NASA s Coastal Zone Color Scanner, launched in 1978, was the first ocean color instrument flown on a spacecraft. Since then, the Agency s ocean color research capabilities have become increasingly sophisticated with the launch of the SeaWiFS instrument in 1997 and the twin MODIS instruments carried into orbit on NASA s Terra (1999) and Aqua (2002) satellites. The technology provides sweeping, global information on ocean color on a scale unattainable by any other means. One issue that arises from

  13. Abrasive supply for ancient Egypt revealed

    International Nuclear Information System (INIS)

    Peltz, C.; Bichler, M.

    2008-01-01

    In the framework of the major research scheme 'Synchronization of Civilizations in the Eastern Mediterranean Region in the 2nd Millennium B.C' instrumental neutron activation analysis (INAA) was used to determine 30 elements in pumice from archaeological excavations to reveal their specific volcanic origin. In ancient time, the widespread pumiceous products of several eruptions in the Aegean region have been used as abrasive tools and were therefore popular trade objects. The correlation of such archaeological findings to a specific eruption of known age would therefore allow to certify a maximum age of the respective stratum ('dating by first appearance'). Pumices from the Aegean region can easily be distinguished by their trace element distribution patterns. This has been shown by previous studies of the group. The elements Al, Ba, Ca, Ce, Co, Cr, Cs, Dy, Eu, Fe, Hf, K, La, Lu, Mn, Na, Nd, Rb, Sb, Sc, Sm, Ta, Tb, Th, Ti, U, V, Yb, Zr and Zn were determined in 16 samples of pumice lumps from excavations in Tell-el-Dab'a and Tell-el-Herr (Egypt). Two irradiation cycles and five measurement runs were applied. To show the accuracy of the results obtained, typical samples of the most important pumice sources in the Aegean region, particularly from Milos, Nisyros, Kos and Thera were analyzed together with the Egyptian samples of unknown origin. A reliable identification of the samples is achieved by comparing these results to the database compiled in previous studies. The geographical positions of these islands are shown. Within the error range, most of the elements determined in typical representatives of Milos, Nisyros, Kos and Santorini were in perfect agreement with values from the literature. On the basis of the Cluster graphics presented, it is possible to relate unknown pumice to its primary source, just by comparing the relation of a few elements, like Ta-Eu and Th-Hf. One concludes that all samples except one can be related to the Minoan eruption of Thera

  14. Dramatic Outburst Reveals Nearest Black Hole

    Science.gov (United States)

    2000-01-01

    Sgr. The radio observations revealed the presence of a jet escaping from the system at mind-boggling speeds. Only three other galactic X-ray stellar systems have been found to eject material at such speeds. They have been dubbed "microquasars" because, on a smaller scale, they resemble quasars, which lie at the hearts of distant galaxies and also spew out high-velocity jets of particles. In galaxy-core quasars, the black holes are millions of times more massive than the Sun; in the more nearby microquasars the black holes are roughly three to twenty times more massive than the Sun. The extremely high velocity of the jets suggests that their origin lies close to the event horizon of a black hole. Microquasar activity is thought to arise when the black hole in the binary system draws material away from its companion star. The material surrounding the black hole forms a rapidly spinning disk called an accretion disk. This disk is heated by friction to millions of degrees, causing it to emit X-rays. As spiralling gas moves into the gravity well of the black hole, it moves faster and faster. Magnetic fields in the disk are believed to expel the charged subatomic particles at speeds close to that of light. As the charged particles interact with the magnetic fields, they emit radio waves. If some of the material escapes by being magnetically expelled into space, the matter may continue moving at the tremendous speed it had attained near the black hole. After their ejection, the jets of particles expand and cool, fading from astronomers' view. V4641 Sgr excites astronomers because it is close and because it acted so differently from other microquasars. In other microquasars, outbursts have dimmed more slowly over weeks or months rather than hours. "There's something fundamentally different about this one; it's more extreme than any other example," Hjellming said. "And because this system happens to be so close to us, `it is very likely that there are more objects like V4641

  15. Control Areas

    Data.gov (United States)

    Department of Homeland Security — This feature class represents electric power Control Areas. Control Areas, also known as Balancing Authority Areas, are controlled by Balancing Authorities, who are...

  16. Control of control charts

    NARCIS (Netherlands)

    Sri Nurdiati, S.N.

    2005-01-01

    Although the Shewhart chart is widely used in practice because of its simplicity, applying this control chart to monitor the mean of a process may lead to two types of problems. The first concerns the typically unknown parameters involved in the distribution, while the second concerns the validity

  17. Comparative genomics of neuroglobin reveals its early origins.

    Directory of Open Access Journals (Sweden)

    Jasmin Dröge

    Full Text Available Neuroglobin (Ngb is a hexacoordinated globin expressed mainly in the central and peripheral nervous system of vertebrates. Although several hypotheses have been put forward regarding the role of neuroglobin, its definite function remains uncertain. Ngb appears to have a neuro-protective role enhancing cell viability under hypoxia and other types of oxidative stress. Ngb is phylogenetically ancient and has a substitution rate nearly four times lower than that of other vertebrate globins, e.g. hemoglobin. Despite its high sequence conservation among vertebrates Ngb seems to be elusive in invertebrates.We determined candidate orthologs in invertebrates and identified a globin of the placozoan Trichoplax adhaerens that is most likely orthologous to vertebrate Ngb and confirmed the orthologous relationship of the polymeric globin of the sea urchin Strongylocentrotus purpuratus to Ngb. The putative orthologous globin genes are located next to genes orthologous to vertebrate POMT2 similarly to localization of vertebrate Ngb. The shared syntenic position of the globins from Trichoplax, the sea urchin and of vertebrate Ngb strongly suggests that they are orthologous. A search for conserved transcription factor binding sites (TFBSs in the promoter regions of the Ngb genes of different vertebrates via phylogenetic footprinting revealed several TFBSs, which may contribute to the specific expression of Ngb, whereas a comparative analysis with myoglobin revealed several common TFBSs, suggestive of regulatory mechanisms common to globin genes.Identification of the placozoan and echinoderm genes orthologous to vertebrate neuroglobin strongly supports the hypothesis of the early evolutionary origin of this globin, as it shows that neuroglobin was already present in the placozoan-bilaterian last common ancestor. Computational determination of the transcription factor binding sites repertoire provides on the one hand a set of transcriptional factors that are

  18. Next generation sequencing reveals the hidden diversity of zooplankton assemblages.

    Directory of Open Access Journals (Sweden)

    Penelope K Lindeque

    Full Text Available BACKGROUND: Zooplankton play an important role in our oceans, in biogeochemical cycling and providing a food source for commercially important fish larvae. However, difficulties in correctly identifying zooplankton hinder our understanding of their roles in marine ecosystem functioning, and can prevent detection of long term changes in their community structure. The advent of massively parallel next generation sequencing technology allows DNA sequence data to be recovered directly from whole community samples. Here we assess the ability of such sequencing to quantify richness and diversity of a mixed zooplankton assemblage from a productive time series site in the Western English Channel. METHODOLOGY/PRINCIPLE FINDINGS: Plankton net hauls (200 µm were taken at the Western Channel Observatory station L4 in September 2010 and January 2011. These samples were analysed by microscopy and metagenetic analysis of the 18S nuclear small subunit ribosomal RNA gene using the 454 pyrosequencing platform. Following quality control a total of 419,041 sequences were obtained for all samples. The sequences clustered into 205 operational taxonomic units using a 97% similarity cut-off. Allocation of taxonomy by comparison with the National Centre for Biotechnology Information database identified 135 OTUs to species level, 11 to genus level and 1 to order, <2.5% of sequences were classified as unknowns. By comparison a skilled microscopic analyst was able to routinely enumerate only 58 taxonomic groups. CONCLUSIONS: Metagenetics reveals a previously hidden taxonomic richness, especially for Copepoda and hard-to-identify meroplankton such as Bivalvia, Gastropoda and Polychaeta. It also reveals rare species and parasites. We conclude that Next Generation Sequencing of 18S amplicons is a powerful tool for elucidating the true diversity and species richness of zooplankton communities. While this approach allows for broad diversity assessments of plankton it may

  19. Memory functions reveal structural properties of gene regulatory networks

    Science.gov (United States)

    Perez-Carrasco, Ruben

    2018-01-01

    Gene regulatory networks (GRNs) control cellular function and decision making during tissue development and homeostasis. Mathematical tools based on dynamical systems theory are often used to model these networks, but the size and complexity of these models mean that their behaviour is not always intuitive and the underlying mechanisms can be difficult to decipher. For this reason, methods that simplify and aid exploration of complex networks are necessary. To this end we develop a broadly applicable form of the Zwanzig-Mori projection. By first converting a thermodynamic state ensemble model of gene regulation into mass action reactions we derive a general method that produces a set of time evolution equations for a subset of components of a network. The influence of the rest of the network, the bulk, is captured by memory functions that describe how the subnetwork reacts to its own past state via components in the bulk. These memory functions provide probes of near-steady state dynamics, revealing information not easily accessible otherwise. We illustrate the method on a simple cross-repressive transcriptional motif to show that memory functions not only simplify the analysis of the subnetwork but also have a natural interpretation. We then apply the approach to a GRN from the vertebrate neural tube, a well characterised developmental transcriptional network composed of four interacting transcription factors. The memory functions reveal the function of specific links within the neural tube network and identify features of the regulatory structure that specifically increase the robustness of the network to initial conditions. Taken together, the study provides evidence that Zwanzig-Mori projections offer powerful and effective tools for simplifying and exploring the behaviour of GRNs. PMID:29470492

  20. Dream controller

    Science.gov (United States)

    Cheng, George Shu-Xing; Mulkey, Steven L; Wang, Qiang; Chow, Andrew J

    2013-11-26

    A method and apparatus for intelligently controlling continuous process variables. A Dream Controller comprises an Intelligent Engine mechanism and a number of Model-Free Adaptive (MFA) controllers, each of which is suitable to control a process with specific behaviors. The Intelligent Engine can automatically select the appropriate MFA controller and its parameters so that the Dream Controller can be easily used by people with limited control experience and those who do not have the time to commission, tune, and maintain automatic controllers.

  1. Controllable dose; Dosis controlable

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez R, J T; Anaya M, R A [ININ, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

    2004-07-01

    With the purpose of eliminating the controversy about the lineal hypothesis without threshold which found the systems of dose limitation of the recommendations of ICRP 26 and 60, at the end of last decade R. Clarke president of the ICRP proposed the concept of Controllable Dose: as the dose or dose sum that an individual receives from a particular source which can be reasonably controllable by means of any means; said concept proposes a change in the philosophy of the radiological protection of its concern by social approaches to an individual focus. In this work a panorama of the foundations is presented, convenient and inconveniences that this proposal has loosened in the international community of the radiological protection, with the purpose of to familiarize to our Mexican community in radiological protection with these new concepts. (Author)

  2. "Wonderful" Star Reveals its Hot Nature

    Science.gov (United States)

    2005-04-01

    to become a white dwarf. The internal turmoil in Mira A could create magnetic disturbances in the upper atmosphere of the star and lead to the observed X-ray outbursts, as well as the rapid loss of material from the star in a blustery, strong, stellar wind. Some of the gas and dust escaping from Mira A is captured by its companion Mira B. In stark contrast to Mira A, Mira B is thought to be a white dwarf star about the size of the Earth. Some of the material in the wind from Mira A is captured in an accretion disk around Mira B, where collisions between rapidly moving particles produce X-rays. Animation of Interacting Stars Animation of Interacting Stars One of the more intriguing aspects of the observations of Mira AB at both X-ray and ultraviolet wavelengths is the evidence for a faint bridge of material joining the two stars. The existence of a bridge would indicate that, in addition to capturing material from the stellar wind, Mira B is also pulling material directly off Mira A into the accretion disk. Chandra observed Mira with its Advanced CCD Imaging Spectrometer on December 6, 2003 for about 19 hours. NASA's Marshall Space Flight Center, Huntsville, Ala., manages the Chandra program for NASA's Science Mission Directorate, Washington. Northrop Grumman of Redondo Beach, Calif., was the prime development contractor for the observatory. The Smithsonian Astrophysical Observatory controls science and flight operations from the Chandra X-ray Center in Cambridge, Mass. Additional information and images are available at: http://chandra.harvard.edu and http://chandra.nasa.gov

  3. Genetic Diversity of Aromatic Rice Germplasm Revealed By SSR Markers

    Directory of Open Access Journals (Sweden)

    Saba Jasim Aljumaili

    2018-01-01

    Full Text Available Aromatic rice cultivars constitute a small but special group of rice and are considered the best in terms of quality and aroma. Aroma is one of the most significant quality traits of rice, and variety with aroma has a higher price in the market. This research was carried out to study the genetic diversity among the 50 aromatic rice accessions from three regions (Peninsular Malaysia, Sabah, and Sarawak with 3 released varieties as a control using the 32 simple sequence repeat (SSR markers. The objectives of this research were to quantify the genetic divergence of aromatic rice accessions using SSR markers and to identify the potential accessions for introgression into the existing rice breeding program. Genetic diversity index among the three populations such as Shannon information index (I ranged from 0.25 in control to 0.98 in Sabah population. The mean numbers of effective alleles and Shannon’s information index were 0.36 and 64.90%, respectively. Similarly, the allelic diversity was very high with mean expected heterozygosity (He of 0.60 and mean Nei’s gene diversity index of 0.36. The dendrogram based on UPGMA and Nei’s genetic distance classified the 53 rice accessions into 10 clusters. Analysis of molecular variance (AMOVA revealed that 89% of the total variation observed in this germplasm came from within the populations, while 11% of the variation emanated among the populations. These results reflect the high genetic differentiation existing in this aromatic rice germplasm. Using all these criteria and indices, seven accessions (Acc9993, Acc6288, Acc6893, Acc7580, Acc6009, Acc9956, and Acc11816 from three populations have been identified and selected for further evaluation before introgression into the existing breeding program and for future aromatic rice varietal development.

  4. Genetic Diversity of Aromatic Rice Germplasm Revealed By SSR Markers.

    Science.gov (United States)

    Jasim Aljumaili, Saba; Rafii, M Y; Latif, M A; Sakimin, Siti Zaharah; Arolu, Ibrahim Wasiu; Miah, Gous

    2018-01-01

    Aromatic rice cultivars constitute a small but special group of rice and are considered the best in terms of quality and aroma. Aroma is one of the most significant quality traits of rice, and variety with aroma has a higher price in the market. This research was carried out to study the genetic diversity among the 50 aromatic rice accessions from three regions (Peninsular Malaysia, Sabah, and Sarawak) with 3 released varieties as a control using the 32 simple sequence repeat (SSR) markers. The objectives of this research were to quantify the genetic divergence of aromatic rice accessions using SSR markers and to identify the potential accessions for introgression into the existing rice breeding program. Genetic diversity index among the three populations such as Shannon information index ( I ) ranged from 0.25 in control to 0.98 in Sabah population. The mean numbers of effective alleles and Shannon's information index were 0.36 and 64.90%, respectively. Similarly, the allelic diversity was very high with mean expected heterozygosity ( H e ) of 0.60 and mean Nei's gene diversity index of 0.36. The dendrogram based on UPGMA and Nei's genetic distance classified the 53 rice accessions into 10 clusters. Analysis of molecular variance (AMOVA) revealed that 89% of the total variation observed in this germplasm came from within the populations, while 11% of the variation emanated among the populations. These results reflect the high genetic differentiation existing in this aromatic rice germplasm. Using all these criteria and indices, seven accessions (Acc9993, Acc6288, Acc6893, Acc7580, Acc6009, Acc9956, and Acc11816) from three populations have been identified and selected for further evaluation before introgression into the existing breeding program and for future aromatic rice varietal development.

  5. Genetic Diversity of Aromatic Rice Germplasm Revealed By SSR Markers

    Science.gov (United States)

    Jasim Aljumaili, Saba; Sakimin, Siti Zaharah; Arolu, Ibrahim Wasiu; Miah, Gous

    2018-01-01

    Aromatic rice cultivars constitute a small but special group of rice and are considered the best in terms of quality and aroma. Aroma is one of the most significant quality traits of rice, and variety with aroma has a higher price in the market. This research was carried out to study the genetic diversity among the 50 aromatic rice accessions from three regions (Peninsular Malaysia, Sabah, and Sarawak) with 3 released varieties as a control using the 32 simple sequence repeat (SSR) markers. The objectives of this research were to quantify the genetic divergence of aromatic rice accessions using SSR markers and to identify the potential accessions for introgression into the existing rice breeding program. Genetic diversity index among the three populations such as Shannon information index (I) ranged from 0.25 in control to 0.98 in Sabah population. The mean numbers of effective alleles and Shannon's information index were 0.36 and 64.90%, respectively. Similarly, the allelic diversity was very high with mean expected heterozygosity (He) of 0.60 and mean Nei's gene diversity index of 0.36. The dendrogram based on UPGMA and Nei's genetic distance classified the 53 rice accessions into 10 clusters. Analysis of molecular variance (AMOVA) revealed that 89% of the total variation observed in this germplasm came from within the populations, while 11% of the variation emanated among the populations. These results reflect the high genetic differentiation existing in this aromatic rice germplasm. Using all these criteria and indices, seven accessions (Acc9993, Acc6288, Acc6893, Acc7580, Acc6009, Acc9956, and Acc11816) from three populations have been identified and selected for further evaluation before introgression into the existing breeding program and for future aromatic rice varietal development. PMID:29736396

  6. Exploring the Musical Taste of Expert Listeners: Musicology Students reveal Tendency towards Omnivorous Taste

    Directory of Open Access Journals (Sweden)

    Paul eElvers

    2015-08-01

    Full Text Available The current study examined the musical taste of musicology students as compared to a control student group. Participants (n=1003 completed an online survey regarding the frequency with which they listened to 22 musical styles. A factor analysis revealed six underlying dimensions of musical taste. A hierarchical cluster analysis then grouped all participants, regardless of their status, according to their similarity on these dimensions. The employed exploratory approach was expected to reveal potential differences between musicology students and controls. A three-cluster solution was obtained. Comparisons of the clusters in terms of musical taste revealed differences in the listening frequency and variety of appreciated music styles: The first cluster (51% musicology students / 27% controls showed the greatest musical engagement across all dimensions although with a tendency towards »sophisticated« musical styles. The second cluster (36% musicology students / 46% controls exhibited an interest in »conventional« music, while the third cluster (13% musicology students / 27% controls showed a strong liking of rock music. The results provide some support for the notion of specific tendencies in the musical taste of musicology students and the contribution of familiarity and knowledge towards musical omnivorousness.

  7. Revealing the hidden structural phases of FeRh

    Science.gov (United States)

    Kim, Jinwoong; Ramesh, R.; Kioussis, Nicholas

    2016-11-01

    Ab initio electronic structure calculations reveal that tetragonal distortion has a dramatic effect on the relative stability of the various magnetic structures (C-, A-, G-, A'-AFM, and FM) of FeRh giving rise to a wide range of novel stable/metastable structures and magnetic phase transitions between these states. We predict that the cubic G-AFM structure, which was believed thus far to be the ground state, is metastable and that the tetragonally expanded G-AFM is the stable structure. The low energy barrier separating these states suggests phase coexistence at room temperature. We propose an A'-AFM phase to be the global ground state among all magnetic phases which arises from the strain-induced tuning of the exchange interactions. The results elucidate the underlying mechanism for the recent experimental findings of electric-field control of magnetic phase transition driven via tetragonal strain. The magnetic phase transitions open interesting prospects for exploiting strain engineering for the next-generation memory devices.

  8. Wetland Microtopographic Structure is Revealed with Terrestrial Laser Scanning

    Science.gov (United States)

    Diamond, J.; Stovall, A. E.; Mclaughlin, D. L.; Slesak, R.

    2017-12-01

    Wetland microtopographic structure and its function has been the subject of research for decades, and several investigations suggest that microtopography is generated by autogenic ecohydrologic processes. But due to the difficulty of capturing the true spatial variability of wetland microtopography, many of the hypotheses for self-organization have remained elusive to test. We employ a novel method of Terrestrial Laser Scanning (TLS) that reveals an unprecedented high-resolution (structure of wetland microtopography in 10 black ash (Fraxinus nigra) stands of northern Minnesota, USA. Here we present the first efforts to synthesize this information and show that TLS provides a good representation of real microtopographic structure, where TLS accurately measured hummock height, but occlusion of low points led to a slight negative bias. We further show that TLS can accurately locate microtopographic high points (hummocks), as well as estimate their height and area. Using these new data, we estimate distributions in both microtopographic elevation and hummock area in each wetland and relate these to monitored hydrologic regime; in doing so, we test hypotheses linking emergent microtopographic patterns to putative hydrologic controls. Finally, we discuss future efforts to enumerate consequent influences of microtopography on wetland systems (soil properties and vegetation composition).

  9. Sex-ratio control erodes sexual selection, revealing evolutionary feedback from adaptive plasticity

    NARCIS (Netherlands)

    Fawcett, Tim W.; Kuijper, Bram; Weissing, Franz J.; Pen, Ido

    2011-01-01

    Female choice is a powerful selective force, driving the elaboration of conspicuous male ornaments. This process of sexual selection has profound implications for many life-history decisions, including sex allocation. For example, females with attractive partners should produce more sons, because

  10. Stress barriers controlling lateral migration of magma revealed by seismic tomography

    OpenAIRE

    Mart?, J.; Villase?or, A.; Geyer, A.; L?pez, C.; Tryggvason, A.

    2017-01-01

    Understanding how monogenetic volcanic systems work requires full comprehension of the local and regional stresses that govern magma migration inside them and why/how they seem to change from one eruption to another. During the 2011-2012 El Hierro eruption (Canary Islands) the characteristics of unrest, including a continuous change in the location of seismicity, made the location of the future vent unpredictable, so short term hazard assessment was highly imprecise. A 3D P-wave velocity mode...

  11. Genome-wide analysis reveals a cell cycle–dependent mechanism controlling centromere propagation

    Science.gov (United States)

    Erhardt, Sylvia; Mellone, Barbara G.; Betts, Craig M.; Zhang, Weiguo; Karpen, Gary H.; Straight, Aaron F.

    2008-01-01

    Centromeres are the structural and functional foundation for kinetochore formation, spindle attachment, and chromosome segregation. In this study, we isolated factors required for centromere propagation using genome-wide RNA interference screening for defects in centromere protein A (CENP-A; centromere identifier [CID]) localization in Drosophila melanogaster. We identified the proteins CAL1 and CENP-C as essential factors for CID assembly at the centromere. CID, CAL1, and CENP-C coimmunoprecipitate and are mutually dependent for centromere localization and function. We also identified the mitotic cyclin A (CYCA) and the anaphase-promoting complex (APC) inhibitor RCA1/Emi1 as regulators of centromere propagation. We show that CYCA is centromere localized and that CYCA and RCA1/Emi1 couple centromere assembly to the cell cycle through regulation of the fizzy-related/CDH1 subunit of the APC. Our findings identify essential components of the epigenetic machinery that ensures proper specification and propagation of the centromere and suggest a mechanism for coordinating centromere inheritance with cell division. PMID:19047461

  12. Genome-wide analysis reveals a cell cycle-dependent mechanism controlling centromere propagation.

    Science.gov (United States)

    Erhardt, Sylvia; Mellone, Barbara G; Betts, Craig M; Zhang, Weiguo; Karpen, Gary H; Straight, Aaron F

    2008-12-01

    Centromeres are the structural and functional foundation for kinetochore formation, spindle attachment, and chromosome segregation. In this study, we isolated factors required for centromere propagation using genome-wide RNA interference screening for defects in centromere protein A (CENP-A; centromere identifier [CID]) localization in Drosophila melanogaster. We identified the proteins CAL1 and CENP-C as essential factors for CID assembly at the centromere. CID, CAL1, and CENP-C coimmunoprecipitate and are mutually dependent for centromere localization and function. We also identified the mitotic cyclin A (CYCA) and the anaphase-promoting complex (APC) inhibitor RCA1/Emi1 as regulators of centromere propagation. We show that CYCA is centromere localized and that CYCA and RCA1/Emi1 couple centromere assembly to the cell cycle through regulation of the fizzy-related/CDH1 subunit of the APC. Our findings identify essential components of the epigenetic machinery that ensures proper specification and propagation of the centromere and suggest a mechanism for coordinating centromere inheritance with cell division.

  13. Mechanism governing heme synthesis reveals a GATA factor/heme circuit that controls differentiation.

    Science.gov (United States)

    Tanimura, Nobuyuki; Miller, Eli; Igarashi, Kazuhiko; Yang, David; Burstyn, Judith N; Dewey, Colin N; Bresnick, Emery H

    2016-02-01

    Metal ion-containing macromolecules have fundamental roles in essentially all biological processes throughout the evolutionary tree. For example, iron-containing heme is a cofactor in enzyme catalysis and electron transfer and an essential hemoglobin constituent. To meet the intense demand for hemoglobin assembly in red blood cells, the cell type-specific factor GATA-1 activates transcription of Alas2, encoding the rate-limiting enzyme in heme biosynthesis, 5-aminolevulinic acid synthase-2 (ALAS-2). Using genetic editing to unravel mechanisms governing heme biosynthesis, we discovered a GATA factor- and heme-dependent circuit that establishes the erythroid cell transcriptome. CRISPR/Cas9-mediated ablation of two Alas2 intronic cis elements strongly reduces GATA-1-induced Alas2 transcription, heme biosynthesis, and surprisingly, GATA-1 regulation of other vital constituents of the erythroid cell transcriptome. Bypassing ALAS-2 function in Alas2 cis element-mutant cells by providing its catalytic product 5-aminolevulinic acid rescues heme biosynthesis and the GATA-1-dependent genetic network. Heme amplifies GATA-1 function by downregulating the heme-sensing transcriptional repressor Bach1 and via a Bach1-insensitive mechanism. Through this dual mechanism, heme and a master regulator collaborate to orchestrate a cell type-specific transcriptional program that promotes cellular differentiation. © 2015 The Authors.

  14. Nitric Oxide Synthases Reveal a Role for Calmodulin in Controlling Electron Transfer

    Science.gov (United States)

    Abu-Soud, Husam M.; Stuehr, Dennis J.

    1993-11-01

    Nitric oxide (NO) is synthesized within the immune, vascular, and nervous systems, where it acts as a wide-ranging mediator of mammalian physiology. The NO synthases (EC 1.14.13.39) isolated from neurons or endothelium are calmodulin dependent. Calmodulin binds reversibly to neuronal NO synthase in response to elevated Ca2+, triggering its NO production by an unknown mechanism. Here we show that calmodulin binding allows NADPH-derived electrons to pass onto the heme group of neuronal NO synthase. Calmodulin-triggered electron transfer to heme was independent of substrate binding, caused rapid enzymatic oxidation of NADPH in the presence of O_2, and was required for NO synthesis. An NO synthase isolated from cytokine-induced macrophages that contains tightly bound calmodulin catalyzed spontaneous electron transfer to its heme, consistent with bound calmodulin also enabling electron transfer within this isoform. Together, these results provide a basis for how calmodulin may regulate NO synthesis. The ability of calmodulin to trigger electron transfer within an enzyme is unexpected and represents an additional function for calcium-binding proteins in biology.

  15. Lithological control on gas hydrate saturation as revealed by signal classification of NMR logging data

    Science.gov (United States)

    Bauer, Klaus; Kulenkampff, Johannes; Henninges, Jan; Spangenberg, Erik

    2015-09-01

    In this paper, nuclear magnetic resonance (NMR) downhole logging data are analyzed with a new strategy to study gas hydrate-bearing sediments in the Mackenzie Delta (NW Canada). In NMR logging, transverse relaxation time (T2) distribution curves are usually used to determine single-valued parameters such as apparent total porosity or hydrocarbon saturation. Our approach analyzes the entire T2 distribution curves as quasi-continuous signals to characterize the rock formation. We apply self-organizing maps, a neural network clustering technique, to subdivide the data set of NMR curves into classes with a similar and distinctive signal shape. The method includes (1) preparation of data vectors, (2) unsupervised learning, (3) cluster definition, and (4) classification and depth mapping of all NMR signals. Each signal class thus represents a specific pore size distribution which can be interpreted in terms of distinct lithologies and reservoir types. A key step in the interpretation strategy is to reconcile the NMR classes with other log data not considered in the clustering analysis, such as gamma ray, hydrate saturation, and other logs. Our results defined six main lithologies within the target zone. Gas hydrate layers were recognized by their low signal amplitudes for all relaxation times. Most importantly, two subtypes of hydrate-bearing shaly sands were identified. They show distinct NMR signals and differ in hydrate saturation and gamma ray values. An inverse linear relationship between hydrate saturation and clay content was concluded. Finally, we infer that the gas hydrate is not grain coating, but rather, pore filling with matrix support is the preferred growth habit model for the studied formation.

  16. Spatially resolved metabolic analysis reveals a central role for transcriptional control in carbon allocation to wood.

    Science.gov (United States)

    Roach, Melissa; Arrivault, Stéphanie; Mahboubi, Amir; Krohn, Nicole; Sulpice, Ronan; Stitt, Mark; Niittylä, Totte

    2017-06-15

    The contribution of transcriptional and post-transcriptional regulation to modifying carbon allocation to developing wood of trees is not well defined. To clarify the role of transcriptional regulation, the enzyme activity patterns of eight central primary metabolism enzymes across phloem, cambium, and developing wood of aspen (Populus tremula L.) were compared with transcript levels obtained by RNA sequencing of sequential stem sections from the same trees. Enzymes were selected on the basis of their importance in sugar metabolism and in linking primary metabolism to lignin biosynthesis. Existing enzyme assays were adapted to allow measurements from ~1 mm3 sections of dissected stem tissue. These experiments provided high spatial resolution of enzyme activity changes across different stages of wood development, and identified the gene transcripts probably responsible for these changes. In most cases, there was a clear positive relationship between transcripts and enzyme activity. During secondary cell wall formation, the increases in transcript levels and enzyme activities also matched with increased levels of glucose, fructose, hexose phosphates, and UDP-glucose, emphasizing an important role for transcriptional regulation in carbon allocation to developing aspen wood. These observations corroborate the efforts to increase carbon allocation to wood by engineering gene regulatory networks. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  17. Dynamics of DNA replication loops reveal temporal control of lagging-strand synthesis

    NARCIS (Netherlands)

    Hamdan, Samir M.; Loparo, Joseph J.; Takahashi, Masateru; Richardson, Charles C.; Oijen, Antoine M. van

    2009-01-01

    In all organisms, the protein machinery responsible for the replication of DNA, the replisome, is faced with a directionality problem. The antiparallel nature of duplex DNA permits the leading-strand polymerase to advance in a continuous fashion, but forces the lagging-strand polymerase to

  18. Heat exchange from the toucan bill reveals a controllable vascular thermal radiator.

    Science.gov (United States)

    Tattersall, Glenn J; Andrade, Denis V; Abe, Augusto S

    2009-07-24

    The toco toucan (Ramphastos toco), the largest member of the toucan family, possesses the largest beak relative to body size of all birds. This exaggerated feature has received various interpretations, from serving as a sexual ornament to being a refined adaptation for feeding. However, it is also a significant surface area for heat exchange. Here we show the remarkable capacity of the toco toucan to regulate heat distribution by modifying blood flow, using the bill as a transient thermal radiator. Our results indicate that the toucan's bill is, relative to its size, one of the largest thermal windows in the animal kingdom, rivaling elephants' ears in its ability to radiate body heat.

  19. A Landscape of Therapeutic Cooperativity in KRAS Mutant Cancers Reveals Principles for Controlling Tumor Evolution

    OpenAIRE

    Grace R. Anderson; Peter S. Winter; Kevin H. Lin; Daniel P. Nussbaum; Merve Cakir; Elizabeth M. Stein; Ryan S. Soderquist; Lorin Crawford; Jim C. Leeds; Rachel Newcomb; Priya Stepp; Catherine Yip; Suzanne E. Wardell; Jennifer P. Tingley; Moiez Ali

    2017-01-01

    Combinatorial inhibition of effector and feedback pathways is a promising treatment strategy for KRAS mutant cancers. However, the particular pathways that should be targeted to optimize therapeutic responses are unclear. Using CRISPR/Cas9, we systematically mapped the pathways whose inhibition cooperates with drugs targeting the KRAS effectors MEK, ERK, and PI3K. By performing 70 screens in models of KRAS mutant colorectal, lung, ovarian, and pancreas cancers, we uncovered universal and tiss...

  20. Mosquito Control

    Science.gov (United States)

    ... Labs and Research Centers Contact Us Share Mosquito Control About Mosquitoes General Information Life Cycle Information from ... Repellent that is Right for You DEET Mosquito Control Methods Success in mosquito control: an integrated approach ...

  1. Birth Control

    Science.gov (United States)

    Birth control, also known as contraception, is designed to prevent pregnancy. Birth control methods may work in a number of different ... eggs that could be fertilized. Types include birth control pills, patches, shots, vaginal rings, and emergency contraceptive ...

  2. Controlling You Watching Me: Measuring Perception Control on Social Media.

    Science.gov (United States)

    Keep, Melanie; Attrill-Smith, Alison

    2017-09-01

    Online self-presentation assumes that individuals intentionally control how others perceive them based on their online behaviors. Existing tools are limited in their ability to measure this notion of perception control and there is little understanding around factors which may affect the desire for perception control. This article reports on the development of a perception control scale and comparisons of perception control across age and between genders. A total of 222 participants completed an online survey with items measuring perception control and participant demographics. A principal component analysis revealed a one-factor, 12-item scale explaining 41.14% of the variance. Perception control was found to increase with age and did not differ between genders. Results are consistent with existing impression management research suggesting that while participants of both genders desire to control how others perceive them, as a person's sense of self stabilizes over time, they are less motivated to change their behaviors to control others' impressions of them.

  3. Pushing typists back on the learning curve: revealing chunking in skilled typewriting.

    Science.gov (United States)

    Yamaguchi, Motonori; Logan, Gordon D

    2014-04-01

    Theories of skilled performance propose that highly trained skills involve hierarchically structured control processes. The present study examined and demonstrated hierarchical control at several levels of processing in skilled typewriting. In the first two experiments, we scrambled the order of letters in words to prevent skilled typists from chunking letters, and compared typing words and scrambled words. Experiment 1 manipulated stimulus quality to reveal chunking in perception, and Experiment 2 manipulated concurrent memory load to reveal chunking in short-term memory (STM). Both experiments manipulated the number of letters in words and nonwords to reveal chunking in motor planning. In the next two experiments, we degraded typing skill by altering the usual haptic feedback by using a laser-projection keyboard, so that typists had to monitor keystrokes. Neither the number of motor chunks (Experiment 3) nor the number of STM items (Experiment 4) was influenced by the manipulation. The results indicate that the utilization of hierarchical control depends on whether the input allows chunking but not on whether the output is generated automatically. We consider the role of automaticity in hierarchical control of skilled performance.

  4. Mesoscopic organization reveals the constraints governing Caenorhabditis elegans nervous system.

    Directory of Open Access Journals (Sweden)

    Raj Kumar Pan

    Full Text Available One of the biggest challenges in biology is to understand how activity at the cellular level of neurons, as a result of their mutual interactions, leads to the observed behavior of an organism responding to a variety of environmental stimuli. Investigating the intermediate or mesoscopic level of organization in the nervous system is a vital step towards understanding how the integration of micro-level dynamics results in macro-level functioning. The coordination of many different co-occurring processes at this level underlies the command and control of overall network activity. In this paper, we have considered the somatic nervous system of the nematode Caenorhabditis elegans, for which the entire neuronal connectivity diagram is known. We focus on the organization of the system into modules, i.e., neuronal groups having relatively higher connection density compared to that of the overall network. We show that this mesoscopic feature cannot be explained exclusively in terms of considerations such as, optimizing for resource constraints (viz., total wiring cost and communication efficiency (i.e., network path length. Even including information about the genetic relatedness of the cells cannot account for the observed modular structure. Comparison with other complex networks designed for efficient transport (of signals or resources implies that neuronal networks form a distinct class. This suggests that the principal function of the network, viz., processing of sensory information resulting in appropriate motor response, may be playing a vital role in determining the connection topology. Using modular spectral analysis we make explicit the intimate relation between function and structure in the nervous system. This is further brought out by identifying functionally critical neurons purely on the basis of patterns of intra- and inter-modular connections. Our study reveals how the design of the nervous system reflects several constraints, including

  5. Rheology of transgenic switchgrass reveals practical aspects of biomass processing.

    Science.gov (United States)

    Wan, Guigui; Frazier, Taylor; Jorgensen, Julianne; Zhao, Bingyu; Frazier, Charles E

    2018-01-01

    Mechanical properties of transgenic switchgrass have practical implications for biorefinery technologies. Presented are fundamentals for simple (thermo)mechanical measurements of genetically transformed switchgrass. Experimental basics are provided for the novice, where the intention is to promote collaboration between plant biologists and materials scientists. Stem sections were subjected to two stress modes: (1) torsional oscillation in the linear response region, and (2) unidirectional torsion to failure. Specimens were analyzed while submerged/saturated in ethylene glycol, simulating natural hydration and allowing experimental temperatures above 100 °C for an improved view of the lignin glass transition. Down-regulation of the 4-Coumarate:coenzyme A ligase gene (reduced lignin content and altered monomer composition) generally resulted in less stiff and weaker stems. These observations were associated with a reduction in the temperature and activation energy of the lignin glass transition, but surprisingly with no difference in the breadth and intensity of the tan  δ signal. The results showed promise in further investigations of how rheological methods relate to stem lignin content, composition, and functional properties in the field and in bioprocessing. Measurements such as these are complicated by small specimen size; however, torsional rheometers (relatively common in polymer laboratories) are well suited for this task. As opposed to the expense and complication of relative humidity control, solvent-submersion rheological methods effectively reveal fundamental structure/property relationships in plant tissues. Demonstrated are low-strain linear methods, and also nonlinear yield and failure analysis; the latter is very uncommon for typical rheological equipment.

  6. Facial cellulitis revealing choreo-acanthocytosis: A case report ...

    African Journals Online (AJOL)

    We report a 62 year-old-man with facial cellulitis revealing choreo-acanthocytosis (ChAc). He showed chorea that started 20 years ago. The orofacial dyskinisia with tongue and cheek biting resulted in facial cellulitis. The peripheral blood smear revealed acanthocytosis of 25%. The overall of chorea, orofacial dyskinetic ...

  7. Whole-genome sequencing reveals a potential causal mutation for dwarfism in the Miniature Shetland pony.

    Science.gov (United States)

    Metzger, Julia; Gast, Alana Christina; Schrimpf, Rahel; Rau, Janina; Eikelberg, Deborah; Beineke, Andreas; Hellige, Maren; Distl, Ottmar

    2017-04-01

    The Miniature Shetland pony represents a horse breed with an extremely small body size. Clinical examination of a dwarf Miniature Shetland pony revealed a lowered size at the withers, malformed skull and brachygnathia superior. Computed tomography (CT) showed a shortened maxilla and a cleft of the hard and soft palate which protruded into the nasal passage leading to breathing difficulties. Pathological examination confirmed these findings but did not reveal histopathological signs of premature ossification in limbs or cranial sutures. Whole-genome sequencing of this dwarf Miniature Shetland pony and comparative sequence analysis using 26 reference equids from NCBI Sequence Read Archive revealed three probably damaging missense variants which could be exclusively found in the affected foal. Validation of these three missense mutations in 159 control horses from different horse breeds and five donkeys revealed only the aggrecan (ACAN)-associated g.94370258G>C variant as homozygous wild-type in all control samples. The dwarf Miniature Shetland pony had the homozygous mutant genotype C/C of the ACAN:g.94370258G>C variant and the normal parents were heterozygous G/C. An unaffected full sib and 3/5 unaffected half-sibs were heterozygous G/C for the ACAN:g.94370258G>C variant. In summary, we could demonstrate a dwarf phenotype in a miniature pony breed perfectly associated with a missense mutation within the ACAN gene.

  8. Dissection of a locus on mouse chromosome 5 reveals arthritis promoting and inhibitory genes

    DEFF Research Database (Denmark)

    Lindvall, Therese; Karlsson, Jenny; Holmdahl, Rikard

    2009-01-01

    with Eae39 congenic- and sub-interval congenic mice, carrying RIIIS/J genes on the B10.RIII genetic background, revealed three loci within Eae39 that control disease and anti-collagen antibody titers. Two of the loci promoted disease and the third locus was protecting from collagen induced arthritis...... development. By further breeding of mice with small congenic fragments, we identified a 3.2 Megabasepair (Mbp) interval that regulates disease. CONCLUSIONS: Disease promoting- and protecting genes within the Eae39 locus on mouse chromosome 5, control susceptibility to collagen induced arthritis. A disease......-protecting locus in the telomeric part of Eae39 results in lower anti-collagen antibody responses. The study shows the importance of breeding sub-congenic mouse strains to reveal genetic effects on complex diseases....

  9. Neurofuzzy Control

    DEFF Research Database (Denmark)

    Jantzen, Jan

    1997-01-01

    These notes are for a course in fuzzy control and neural networks. By neural networks we more precisely mean neurofuzzy systems rather than pure neural network theory. The notes are an extension to the existing notes on fuzzy control (Jantzen, Fuzzy Control, 1994).......These notes are for a course in fuzzy control and neural networks. By neural networks we more precisely mean neurofuzzy systems rather than pure neural network theory. The notes are an extension to the existing notes on fuzzy control (Jantzen, Fuzzy Control, 1994)....

  10. Control rod position control device

    International Nuclear Information System (INIS)

    Ubukata, Shinji.

    1997-01-01

    The present invention provides a control rod position control device which stores data such as of position signals and driving control rod instruction before and after occurrence of abnormality in control for the control rod position for controlling reactor power and utilized the data effectively for investigating the cause of abnormality. Namely, a plurality of individual control devices have an operation mismatching detection circuit for outputting signals when difference is caused between a driving instruction given to the control rod position control device and the control rod driving means and signals from a detection means for detecting an actual moving amount. A general control device collectively controls the individual control devices. In addition, there is also disposed a position storing circuit for storing position signals at least before and after the occurrence of the control rod operation mismatching. With such procedures, the cause of the abnormality can be determined based on the position signals before and after the occurrence of control rod mismatching operation stored in the position storing circuit. Accordingly, the abnormality cause can be determined to conduct restoration in an early stage. (I.S.)

  11. Control rods

    International Nuclear Information System (INIS)

    Maruyama, Hiromi.

    1984-01-01

    Purpose: To realize effective utilization, cost reduction and weight reduction in neutron absorbing materials. Constitution: Residual amount of neutron absorbing material is averaged between the top end region and other regions of a control rod upon reaching to the control rod working life, by using a single kind of neutron absorbing material and increasing the amount of the neutron absorber material at the top end region of the control rod as compared with that in the other regions. Further, in a case of a control rod having control rod blades such as in a cross-like control rod, the amount of the neutron absorbing material is decreased in the middle portion than in the both end portions of the control rod blade along the transversal direction of the rod, so that the residual amount of the neutron absorbing material is balanced between the central region and both end regions upon reaching the working life of the control rod. (Yoshihara, H.)

  12. Radiologically revealed spine osteoporosis in male with hypertension and coronary heart disease

    Directory of Open Access Journals (Sweden)

    P A Chizhov

    2005-01-01

    Full Text Available Radiologically revealed spine osteoporosis in male with hypertension and coronary heart disease Objective. To study prevalence and intensity of spine osteoporosis (OP in men suffering from hypertension (H and coronary heart disease (CHD. Material and methods. 101 men with H and CHD aged 50 to 78 years (mean age 60,6±0,85 years and 37 men of control group without cardiovascular diseases aged 50-66 years (mean age 58,6±0,74 years were examined. Clinical examination, radiological, radiomorphometric spine examination and echocardioscopy were performed. Results. OP was revealed in 34,65% of main group pts what is 3,2 times more frequent than in control group (10,8%, p<0,05. OP intensity in men with H and CHD was significantly higher than in healthy people. Vfertebral fractures were revealed in 12,87+3,3% of main group pts and only in 2,7±2,7% in control group (p<0,05. OP development dependence from cardiac history duration and cardiac pathology severity was demonstrated. Conclusion. The results of the study show significantly higher prevalence of spine OP among men suffering from H and CHD. Long history and severity of cardiovascular pathology clinical signs promote OP frequency and severity increase.

  13. Control apparatus

    International Nuclear Information System (INIS)

    Doll, D.W.

    1977-01-01

    A nuclear reactor system is described in which flexible control rods are used to enable insertion of the control rods into guide holes in the core which are distributed over an area larger than the cross section of the control rod penetration in the reactor pressure vessel. Guide tubes extend from the penetration and fan out to the guide holes for guiding the control rods from the penetration to the guide holes

  14. Gaining control

    NARCIS (Netherlands)

    Enden, van der E.; Laan, van der R.

    2008-01-01

    The article reports on the efforts of companies to find a solution for tax risk management, tax accounting and being in control. In trying to find a solution, companies work towards an integrated tax control framework (TCF), a tax risk management and control environment embedded in the internal

  15. Associational control

    DEFF Research Database (Denmark)

    Hvid, Helge Søndergaard; Lund, Henrik Lambrecht; Grosen, Sidsel Lond

    2010-01-01

    Over the last 30 years, the concept of control has had a central position in research into the psychological working environment. Control has been understood as individual autonomy and individual opportunities for development. This article examines whether the concept of control has the same key...

  16. Exploring the musical taste of expert listeners: musicology students reveal tendency toward omnivorous taste.

    Science.gov (United States)

    Elvers, Paul; Omigie, Diana; Fuhrmann, Wolfgang; Fischinger, Timo

    2015-01-01

    Musicology students are engaged with music on an academic level and usually have an extensive musical background. They have a considerable knowledge of music history and theory and listening to music may be regarded as one of their primary occupations. Taken together, these factors qualify them as ≫expert listeners≪, who may be expected to exhibit a specific profile of musical taste: interest in a broad range of musical styles combined with a greater appreciation of ≫sophisticated≪ styles. The current study examined the musical taste of musicology students as compared to a control student group. Participants (n = 1003) completed an online survey regarding the frequency with which they listened to 22 musical styles. A factor analysis revealed six underlying dimensions of musical taste. A hierarchical cluster analysis then grouped all participants, regardless of their status, according to their similarity on these dimensions. The employed exploratory approach was expected to reveal potential differences between musicology students and controls. A three-cluster solution was obtained. Comparisons of the clusters in terms of musical taste revealed differences in the listening frequency and variety of appreciated music styles: the first cluster (51% musicology students/27% controls) showed the greatest musical engagement across all dimensions although with a tendency toward ≫sophisticated≪ musical styles. The second cluster (36% musicology students/46% controls) exhibited an interest in ≫conventional≪ music, while the third cluster (13% musicology students/27% controls) showed a strong liking of rock music. The results provide some support for the notion of specific tendencies in the musical taste of musicology students and the contribution of familiarity and knowledge toward musical omnivorousness. Further differences between the clusters in terms of social, personality, and sociodemographic factors are discussed.

  17. Paraneoplastic syndromes revealing ovarian teratoma in young and ...

    African Journals Online (AJOL)

    Paraneoplastic syndromes revealing ovarian teratoma in young and menopausal women: report of two cases. Majdouline Boujoual, Ihsan Hakimi, Farid Kassidi, Youssef Akhoudad, Nawal Sahel, Adil Rkiouak, Mohamed Allaoui, Hafsa Chahdi, Mohamed Oukabli, Jaouad Kouach, Driss Rahali Moussaoui, Mohamed ...

  18. DNA markers reveal genetic structure and localized diversity of ...

    African Journals Online (AJOL)

    uqhdesma

    2016-10-12

    Oct 12, 2016 ... STRUCTURE analysis revealed 4 clusters of genetically ..... 10000 cycles and 50000 Markov Chain Monte Carlo (MCMC) iterations and 10 replicate runs performed for each K value to ..... WL, Lee M, Porter K (2000). Genetic ...

  19. Demand effects of consumers’ stated and revealed preferences

    OpenAIRE

    Engström, Per; Forsell, Eskil

    2013-01-01

    Knowledge of how consumers react to different quality signals is fundamental for understanding how markets work. We study the online market- place for Android apps where we compare the causal effects on demand from two quality related signals; other consumers' stated and revealed preferences toward an app. Our main result is that consumers are much more responsive to other consumers' revealed preferences, compared to others' stated preferences. A 10 percentile increase in displayed average ra...

  20. Characteristics of the tomato chromoplast revealed by proteomic analysis

    OpenAIRE

    Barsan, Cristina; Sanchez-Bel, Paloma; Rombaldi, César Valmor; Egea, Isabel; Rossignol, Michel; Kuntz, Marcel; Zouine, Mohamed; Latché, Alain; Bouzayen, Mondher; Pech, Jean-Claude

    2010-01-01

    Chromoplasts are non-photosynthetic specialized plastids that are important in ripening tomato fruit (Solanum lycopersicum) since, among other functions, they are the site of accumulation of coloured compounds. Analysis of the proteome of red fruit chromoplasts revealed the presence of 988 proteins corresponding to 802 Arabidopsis unigenes, among which 209 had not been listed so far in plastidial databanks. These data revealed several features of the chromoplast. Proteins of lipid metabolism ...

  1. Simulation of control drives in a tower crane

    Directory of Open Access Journals (Sweden)

    Wojciech SOLARZ

    2011-01-01

    Full Text Available The design of a control system for a tower crane is investigated. Underlying the controller design is the theory of optimal linear control. Computer models of a crane and the control systems for the crane drives are developed. Simulation data reveals that the motion of the load can be effectively controlled so that it should follow a predetermined trajectory.

  2. Optimal control

    CERN Document Server

    Aschepkov, Leonid T; Kim, Taekyun; Agarwal, Ravi P

    2016-01-01

    This book is based on lectures from a one-year course at the Far Eastern Federal University (Vladivostok, Russia) as well as on workshops on optimal control offered to students at various mathematical departments at the university level. The main themes of the theory of linear and nonlinear systems are considered, including the basic problem of establishing the necessary and sufficient conditions of optimal processes. In the first part of the course, the theory of linear control systems is constructed on the basis of the separation theorem and the concept of a reachability set. The authors prove the closure of a reachability set in the class of piecewise continuous controls, and the problems of controllability, observability, identification, performance and terminal control are also considered. The second part of the course is devoted to nonlinear control systems. Using the method of variations and the Lagrange multipliers rule of nonlinear problems, the authors prove the Pontryagin maximum principle for prob...

  3. Metabonomics revealed xanthine oxidase-induced oxidative stress and inflammation in the pathogenesis of diabetic nephropathy.

    Science.gov (United States)

    Liu, Jingping; Wang, Chengshi; Liu, Fang; Lu, Yanrong; Cheng, Jingqiu

    2015-03-01

    Diabetic nephropathy (DN) is a serious complication of diabetes mellitus (DM), which is a major public health problem in the world. To reveal the metabolic changes associated with DN, we analyzed the serum, urine, and renal extracts obtained from control and streptozotocin (STZ)-induced DN rats by (1)H NMR-based metabonomics and multivariate data analysis. A significant difference between control and DN rats was revealed in metabolic profiles, and we identified several important DN-related metabolites including increased levels of allantoin and uric acid (UA) in the DN rats, suggesting that disturbed purine metabolism may be involved in the DN. Combined with conventional histological and biological methods, we further demonstrated that xanthine oxidase (XO), a key enzyme for purine catabolism, was abnormally activated in the kidney of diabetic rats by hyperglycemia. The highly activated XO increased the level of intracellular ROS, which caused renal injury by direct oxidative damage to renal cells, and indirect inducing inflammatory responses via activating NF-κB signaling pathway. Our study highlighted that metabonomics is a promising tool to reveal the metabolic changes and the underlying mechanism involved in the pathogenesis of DN.

  4. Controlled Noise Seismology

    KAUST Repository

    Hanafy, Sherif M.

    2015-08-19

    We use controlled noise seismology (CNS) to generate surface waves, where we continuously record seismic data while generating artificial noise along the profile line. To generate the CNS data we drove a vehicle around the geophone line and continuously recorded the generated noise. The recorded data set is then correlated over different time windows and the correlograms are stacked together to generate the surface waves. The virtual shot gathers reveal surface waves with moveout velocities that closely approximate those from active source shot gathers.

  5. Controlled Noise Seismology

    KAUST Repository

    Hanafy, Sherif M.; AlTheyab, Abdullah; Schuster, Gerard T.

    2015-01-01

    We use controlled noise seismology (CNS) to generate surface waves, where we continuously record seismic data while generating artificial noise along the profile line. To generate the CNS data we drove a vehicle around the geophone line and continuously recorded the generated noise. The recorded data set is then correlated over different time windows and the correlograms are stacked together to generate the surface waves. The virtual shot gathers reveal surface waves with moveout velocities that closely approximate those from active source shot gathers.

  6. Taking Control

    Centers for Disease Control (CDC) Podcasts

    2007-11-01

    This podcast gives action steps and reasons to control diabetes.  Created: 11/1/2007 by National Diabetes Education Program (NDEP), a joint program of the Centers for Disease Control and Prevention and the National Institutes of Health.   Date Released: 11/2/2007.

  7. Control Theory.

    Science.gov (United States)

    Toso, Robert B.

    2000-01-01

    Inspired by William Glasser's Reality Therapy ideas, Control Theory (CT) is a disciplinary approach that stresses people's ability to control only their own behavior, based on internal motivations to satisfy five basic needs. At one North Dakota high school, CT-trained teachers are the program's best recruiters. (MLH)

  8. CONTROL ROD

    Science.gov (United States)

    Walker, D.E.; Matras, S.

    1963-04-30

    This patent shows a method of making a fuel or control rod for a nuclear reactor. Fuel or control material is placed within a tube and plugs of porous metal wool are inserted at both ends. The metal wool is then compacted and the tube compressed around it as by swaging, thereby making the plugs liquid- impervious but gas-pervious. (AEC)

  9. Birth Control

    Science.gov (United States)

    ... even if you aren’t going for birth control. What doesn’t work to prevent pregnancy? top It’s ... and taking care of a baby’s many needs. What if I need birth control in an emergency? top Emergency contraception (EC) is ...

  10. Integrated controls

    International Nuclear Information System (INIS)

    Hollaway, F.W.

    1985-01-01

    During 1984, all portions of the Nova control system that were necessary for the support of laser activation and completion of the Nova project were finished and placed in service on time. The Nova control system has been unique in providing, on schedule, the capabilities required in the central control room and in various local control areas throughout the facility. The ambitious goal of deploying this system early enough to use it as an aid in the activation of the laser was accomplished; thus the control system made a major contribution to the completion of Nova activation on schedule. Support and enhancement activities continued during the year on the VAX computer systems, central control room, operator consoles and displays, Novanet data communications network, system-level software for both the VAX and LSI-11 computers, Praxis control system computer language, software management tools, and the development system, which includes office terminals. Computational support was also supplied for a wide variety of test fixtures required by the optical and mechanical subsystems. Significant new advancements were made in four areas in integrated controls this year: the integration software (which includes the shot scheduler), the Praxis language, software quality assurance audit, and software development and data handling. A description of the accomplishments in each of these areas follows

  11. Controlling Hypertension

    Centers for Disease Control (CDC) Podcasts

    A recent study found an increase in self-reported high blood pressure among U.S. adults, and an increase in the use of medications to control high blood pressure. This podcast discusses the importance of controlling high blood pressure.

  12. Experiencing control

    NARCIS (Netherlands)

    Monaci, G.; Braspenning, R.A.C.; Meerbeek, B.W.; Bingley, P.; Rajagopalan, R.; Triki, M.

    2009-01-01

    This report describes the activities carried out in the first part of the Experiencing Control project (2008-324). The guiding idea of the project is to make control part of the experience, exploring new interaction solutions for complex, engaging interactions with Philips devices in the living

  13. Control rod

    International Nuclear Information System (INIS)

    Kawakami, Kazuo; Shimoshige, Takanori; Nishimura, Akira

    1979-01-01

    Purpose: A control rod has been developed, which provided a plurality of through-holes in the vicinity of the sheath fitting position, in order to flatten burn-up, of fuel rods in positions confronting a control rod. Thereby to facilitate the manufacture of the control rods and prevent fuel rod failures. Constitution: A plurality of through-holes are formed in the vicinity of the sheath fitting position of a central support rod to which a sheath for the control rod is fitted. These through-holes are arranged in the axial direction of the central support rod. Accordingly, burn-up of fuel rods confronting the control rods can be reduced by through-holes and fuel rod failures can be prevented. (Yoshino, Y.)

  14. Asthma control - Practical suggestions for practicing doctors in family ...

    African Journals Online (AJOL)

    reveals that most patients still had symptoms of asthma, consisting of a cough and a ... that these older studies of asthma control may not reflect the present control .... corticosteroids (ICSs) regularly resulted in falling asthma mortality, upholds ...

  15. UTV Expansion Pack: Special-Purpose Rank-Revealing Algorithms

    DEFF Research Database (Denmark)

    Fierro, Ricardo D.; Hansen, Per Christian

    2005-01-01

    This collection of Matlab 7.0 software supplements and complements the package UTV Tools from 1999, and includes implementations of special-purpose rank-revealing algorithms developed since the publication of the original package. We provide algorithms for computing and modifying symmetric rank-r...... values of a sparse or structured matrix. These new algorithms have applications in signal processing, optimization and LSI information retrieval.......This collection of Matlab 7.0 software supplements and complements the package UTV Tools from 1999, and includes implementations of special-purpose rank-revealing algorithms developed since the publication of the original package. We provide algorithms for computing and modifying symmetric rank......-revealing VSV decompositions, we expand the algorithms for the ULLV decomposition of a matrix pair to handle interference-type problems with a rank-deficient covariance matrix, and we provide a robust and reliable Lanczos algorithm which - despite its simplicity - is able to capture all the dominant singular...

  16. Camelid genomes reveal evolution and adaptation to desert environments.

    Science.gov (United States)

    Wu, Huiguang; Guang, Xuanmin; Al-Fageeh, Mohamed B; Cao, Junwei; Pan, Shengkai; Zhou, Huanmin; Zhang, Li; Abutarboush, Mohammed H; Xing, Yanping; Xie, Zhiyuan; Alshanqeeti, Ali S; Zhang, Yanru; Yao, Qiulin; Al-Shomrani, Badr M; Zhang, Dong; Li, Jiang; Manee, Manee M; Yang, Zili; Yang, Linfeng; Liu, Yiyi; Zhang, Jilin; Altammami, Musaad A; Wang, Shenyuan; Yu, Lili; Zhang, Wenbin; Liu, Sanyang; Ba, La; Liu, Chunxia; Yang, Xukui; Meng, Fanhua; Wang, Shaowei; Li, Lu; Li, Erli; Li, Xueqiong; Wu, Kaifeng; Zhang, Shu; Wang, Junyi; Yin, Ye; Yang, Huanming; Al-Swailem, Abdulaziz M; Wang, Jun

    2014-10-21

    Bactrian camel (Camelus bactrianus), dromedary (Camelus dromedarius) and alpaca (Vicugna pacos) are economically important livestock. Although the Bactrian camel and dromedary are large, typically arid-desert-adapted mammals, alpacas are adapted to plateaus. Here we present high-quality genome sequences of these three species. Our analysis reveals the demographic history of these species since the Tortonian Stage of the Miocene and uncovers a striking correlation between large fluctuations in population size and geological time boundaries. Comparative genomic analysis reveals complex features related to desert adaptations, including fat and water metabolism, stress responses to heat, aridity, intense ultraviolet radiation and choking dust. Transcriptomic analysis of Bactrian camels further reveals unique osmoregulation, osmoprotection and compensatory mechanisms for water reservation underpinned by high blood glucose levels. We hypothesize that these physiological mechanisms represent kidney evolutionary adaptations to the desert environment. This study advances our understanding of camelid evolution and the adaptation of camels to arid-desert environments.

  17. Burned-out seminoma revealed by solitary rib bone metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Nishisho, Toshihiko; Miyagi, Ryo; Sairyo, Koichi [Tokushima University Graduate School, Department of Orthopedics, Institute of Biomedical Sciences, Tokushima-city, Tokushima (Japan); Sakaki, Mika [Saitama Medical University International Medical Center, Department of Pathology, Hidaka-city, Saitama (Japan); Takao, Shoichiro [Tokushima University Graduate School, Department of Radiology, Institute of Biomedical Sciences, Tokushima-city, Tokushima (Japan)

    2017-10-15

    Burned-out tumor is a rare phenomenon in which a testicular tumor regresses in the primary lesion and progresses in a metastatic lesion. We report the case of a 30-year-old male with burned-out seminoma revealed by open biopsy of solitary 10th rib bone metastasis. He underwent inguinal orchiectomy, which revealed hyalinization, indicating a spontaneously regressed testicular tumor. Chemotherapy for seminoma was administered in three cycles of bleomycin + etoposide + cisplatin therapy. The chemotherapy was effective, and wide resection of the rib was subsequently performed. No postoperative chemotherapy was performed, and there has been no evidence of recurrence for 3 years postoperatively. (orig.)

  18. [Postnatal diagnosis of gastric volvulus revealing congenital diaphragmatic hernia].

    Science.gov (United States)

    Aprahamian, A; Nouyrigat, V; Grévent, D; Hervieux, E; Chéron, G

    2017-05-01

    Postnatally diagnosed congenital diaphragmatic hernias (CDH) are rare and have a better prognosis than those diagnosed prenatally. Postnatal symptoms can be respiratory, digestive, or mixed. Gastric volvulus can reveal CDH. Symptoms are pain, abdominal distension, and/or vomiting. Upper gastrointestinal barium X-ray radiography provides the diagnosis. Prognosis is related to early surgical management in complicated forms with intestinal occlusion or sub-occlusion. We report on an infant who presented with vomiting, which revealed gastric volvulus associated with a CDH. Progression was favorable after surgical treatment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Feedback control strategies for the Liu chaotic system

    International Nuclear Information System (INIS)

    Zhu Congxu; Chen Zhigang

    2008-01-01

    This Letter proposed three strategies of the dislocated feedback control, enhancing feedback control and speed feedback control of the Liu chaotic system to its unstable equilibrium points. It is found that the coefficients of enhancing feedback control and speed feedback control are smaller than those of ordinary feedback control, so, the complexity and cost of the system control are reduced. Theoretical analysis and numerical simulation are given, revealing the effectiveness of these strategies

  20. Integrated control of Rapeseed pests

    International Nuclear Information System (INIS)

    Khattak, S.U.; Hamed, M.

    1990-06-01

    Rapeseed crop is attacked by different insects amongst which cabbage butterfly in Pakistan. Integrated control was conducted and results are mentioned in this report. The mortality in the remaining insecticides varied from 55-83% which was significantly higher than control. The higher dosages of gamma radiation ranged between 60-225 krad and results revealed that the mortality response increased with the post-irradiation time. Mortality was also significantly higher at 80-120 krad as compared to control. These results concluded that mortality was dose dependent. (A.B.)

  1. Describing control

    International Nuclear Information System (INIS)

    Fouet, J.M.; Starynkevitch, B.

    1987-01-01

    Incremental development and maintenance of large systems imply that control be clearly separated from knowledge. Finding efficient control for a given class of knowledge is itself a matter of expertise, to which knowledge-based methods may and should be applied. We present here two attempts at building root systems that may later be tuned by knowledge engineers, using the semantics of each particular application. These systems are given heuristics in a declarative manner, which they use to control the application of heuristics. Eventually, some heuristics may be used to compile others (or themselves) into efficient pieces of programmed code

  2. Analysing Access Control Specifications

    DEFF Research Database (Denmark)

    Probst, Christian W.; Hansen, René Rydhof

    2009-01-01

    When prosecuting crimes, the main question to answer is often who had a motive and the possibility to commit the crime. When investigating cyber crimes, the question of possibility is often hard to answer, as in a networked system almost any location can be accessed from almost anywhere. The most...... common tool to answer this question, analysis of log files, faces the problem that the amount of logged data may be overwhelming. This problems gets even worse in the case of insider attacks, where the attacker’s actions usually will be logged as permissible, standard actions—if they are logged at all....... Recent events have revealed intimate knowledge of surveillance and control systems on the side of the attacker, making it often impossible to deduce the identity of an inside attacker from logged data. In this work we present an approach that analyses the access control configuration to identify the set...

  3. Space Movie Reveals Shocking Secrets Of The Crab Pulsa

    Science.gov (United States)

    2002-09-01

    Just when it seemed like the summer movie season had ended, two of NASA's Great Observatories have produced their own action movie. Multiple observations made over several months with NASA's Chandra X-ray Observatory and the Hubble Space Telescope captured the spectacle of matter and antimatter propelled to near the speed of light by the Crab pulsar, a rapidly rotating neutron star the size of Manhattan. "Through this movie, the Crab Nebula has come to life," said Jeff Hester of Arizona State University in Tempe, lead author of a paper in the September 20th issue of The Astrophysical Journal Letters. "We can see how this awesome cosmic generator actually works." The Crab was first observed by Chinese astronomers in 1054 A.D. and has since become one of the most studied objects in the sky. By combining the power of both Chandra and Hubble, the movie reveals features never seen in still images. By understanding the Crab, astronomers hope to unlock the secrets of how similar objects across the universe are powered. Crab Nebula Composite Image Crab Nebula Composite Image Bright wisps can be seen moving outward at half the speed of light to form an expanding ring that is visible in both X-ray and optical images. These wisps appear to originate from a shock wave that shows up as an inner X-ray ring. This ring consists of about two dozen knots that form, brighten and fade, jitter around, and occasionally undergo outbursts that give rise to expanding clouds of particles, but remain in roughly the same location. "These data leave little doubt that the inner X-ray ring is the location of the shock wave that turns the high-speed wind from the pulsar into extremely energetic particles," said Koji Mori of Penn State University in University Park, a coauthor of the paper. Another dramatic feature of the movie is a turbulent jet that lies perpendicular to the inner and outer rings. Violent internal motions are obvious, as is a slow motion outward into the surrounding nebula of

  4. Drug Control

    Science.gov (United States)

    Leviton, Harvey S.

    1975-01-01

    This article attempts to assemble pertinent information about the drug problem, particularily marihuana. It also focuses on the need for an educational program for drug control with the public schools as the main arena. (Author/HMV)

  5. Institutional Controls

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset consists of institutional control data from multiple Superfund sites in U.S. EPA Region 8. These data were acquired from multiple sources at different...

  6. ID-check: Online concealed information test reveals true identity

    NARCIS (Netherlands)

    Verschuere, B.; Kleinberg, B.

    2016-01-01

    The Internet has already changed people's lives considerably and is likely to drastically change forensic research. We developed a web-based test to reveal concealed autobiographical information. Initial studies identified a number of conditions that affect diagnostic efficiency. By combining these

  7. Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

    DEFF Research Database (Denmark)

    Gerlinger, Marco; Rowan, Andrew J.; Horswell, Stuart

    2012-01-01

    .RESULTS: Phylogenetic reconstruction revealed branched evolutionary tumor growth, with 63 to 69% of all somatic mutations not detectable across every tumor region. Intratumor heterogeneity was observed for a mutation within an autoinhibitory domain of the mammalian target of rapamycin (mTOR) kinase, correlating with S6...

  8. Revealing gene action for production characteristics by inbreeding ...

    African Journals Online (AJOL)

    Revealing gene action for production characteristics by inbreeding, based on a long-term selection ... The gene action involved in the expression of production characters was investigated, using the effect of the theoretical inbreeding ..... and predicted selection responses for growth, fat and lean traits in mice. J. Anim. Sci.

  9. An acute adrenal insufficiency revealing pituitary metastases of lung ...

    African Journals Online (AJOL)

    A 69-year-old men presented with vomiting, low blood pressure and hypoglycemia. Hormonal exploration confirmed a hypopituitarism. Appropriate therapy was initiated urgently. The hypothalamic-pituitary MRI showed a pituitary hypertrophy, a nodular thickening of the pituitary stalk. The chest X Rays revealed pulmonary ...

  10. The microbiome of Brazilian mangrove sediments as revealed by metagenomics

    NARCIS (Netherlands)

    Andreote, Fernando Dini; Jiménez Avella, Diego; Chaves, Diego; Dias, Armando Cavalcante Franco; Luvizotto, Danice Mazzer; Dini-Andreote, Francisco; Fasanella, Cristiane Cipola; Lopez, Maryeimy Varon; Baena, Sandra; Taketani, Rodrigo Gouvêa; de Melo, Itamar Soares

    2012-01-01

    Here we embark in a deep metagenomic survey that revealed the taxonomic and potential metabolic pathways aspects of mangrove sediment microbiology. The extraction of DNA from sediment samples and the direct application of pyrosequencing resulted in approximately 215 Mb of data from four distinct

  11. Species Richness and Diversity Reveal that Human-Modified ...

    African Journals Online (AJOL)

    Family diversity and richness showed no significant differences across the sites. The spider species consisted of primarily three functional groups: ground wanderers, web builders and plant wanderers, and showed no within-group differences in abundance between sites. Similarity index between the study sites revealed a ...

  12. Landmark Study Reveals Antarctic Glacier's Long History of Retreat

    OpenAIRE

    Kuska, Dale M.

    2016-01-01

    Faculty Showcase Archive Article Approved for public release; distribution is unlimited. A major study, released in late November in the journal “Nature,” reveals the history of retreat of the massive Pine Island Glacier (PIG) in western Antarctica, widely considered one of the largest contributors to global sea-level rise.

  13. Extensive translational regulation during seed germination revealed by polysomal profiling

    NARCIS (Netherlands)

    Bai, Bing; Peviani, Alessia; Horst, van der Sjors; Gamm, Magdalena; Snel, Berend; Bentsink, Leónie; Hanson, Johannes

    2017-01-01

    This work investigates the extent of translational regulation during seed germination. The polysome occupancy of each gene is determined by genome-wide profiling of total mRNA and polysome-associated mRNA. This reveals extensive translational regulation during Arabidopsis thaliana seed

  14. Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis

    DEFF Research Database (Denmark)

    Miller, Martin Lee; Brunak, Søren; Olsen, JV

    2010-01-01

    and phosphorylation sites were grouped according to their cell cycle kinetics and compared to publicly available messenger RNA microarray data. Most detected phosphorylation sites and more than 20% of all quantified proteins showed substantial regulation, mainly in mitotic cells. Kinase-motif analysis revealed global...

  15. Chemical milling solution reveals stress corrosion cracks in titanium alloy

    Science.gov (United States)

    Braski, D. N.

    1967-01-01

    Solution of hydrogen flouride, hydrogen peroxide, and water reveals hot salt stress corrosion cracks in various titanium alloys. After the surface is rinsed in water, dried, and swabbed with the solution, it can be observed by the naked eye or at low magnification.

  16. Structure defects in malachite revealed by positron annihilation

    International Nuclear Information System (INIS)

    Geffroy, B.; Diallo, I.; Paulin, R.

    1984-01-01

    Positron lifetime is measured between 77 and 400 K in two malachite samples with different mineralogical structures. The complex spectrum found in zoned malachite reveals a microporosity which remains stable in this range of temperature. Besides, above 200 K, equilibrium defects appear. Their formation energy is estimated to be Esub(f) = 0.27 +- 0.02 eV [fr

  17. Structure defects in malachite revealed by positron annihilation

    Energy Technology Data Exchange (ETDEWEB)

    Geffroy, B; Diallo, I; Paulin, R [Institut National des Sciences et Techniques Nucleaires, CEN/Saclay, 91 - Gif-sur-Yvette (France)

    1984-01-01

    Positron lifetime is measured between 77 and 400 K in two malachite samples with different mineralogical structures. The complex spectrum found in zoned malachite reveals a microporosity which remains stable in this range of temperature. Besides, above 200 K, equilibrium defects appear. Their formation energy is estimated to be Esub(f) = 0.27 +- 0.02 eV.

  18. Seasonal succession in zooplankton feeding traits reveals trophic trait coupling

    DEFF Research Database (Denmark)

    Kenitz, Kasia; Visser, Andre; Mariani, Patrizio

    2017-01-01

    non-motile cells flourishing in spring and motile community dominating during summer. The zooplankton community is dominated by active feeding-current feeders with peak biomass in the late spring declining during summer. The model reveals how zooplankton grazing reinforces protist plankton seasonal...

  19. Integrated genomics of Mucorales reveals novel therapeutic targets

    Science.gov (United States)

    Mucormycosis is a life-threatening infection caused by Mucorales fungi. We sequenced 30 fungal genomes and performed transcriptomics with three representative Rhizopus and Mucor strains with human airway epithelial cells during fungal invasion to reveal key host and fungal determinants contributing ...

  20. Adaptation to High Ethanol Reveals Complex Evolutionary Pathways.

    Directory of Open Access Journals (Sweden)

    Karin Voordeckers

    2015-11-01

    Full Text Available Tolerance to high levels of ethanol is an ecologically and industrially relevant phenotype of microbes, but the molecular mechanisms underlying this complex trait remain largely unknown. Here, we use long-term experimental evolution of isogenic yeast populations of different initial ploidy to study adaptation to increasing levels of ethanol. Whole-genome sequencing of more than 30 evolved populations and over 100 adapted clones isolated throughout this two-year evolution experiment revealed how a complex interplay of de novo single nucleotide mutations, copy number variation, ploidy changes, mutator phenotypes, and clonal interference led to a significant increase in ethanol tolerance. Although the specific mutations differ between different evolved lineages, application of a novel computational pipeline, PheNetic, revealed that many mutations target functional modules involved in stress response, cell cycle regulation, DNA repair and respiration. Measuring the fitness effects of selected mutations introduced in non-evolved ethanol-sensitive cells revealed several adaptive mutations that had previously not been implicated in ethanol tolerance, including mutations in PRT1, VPS70 and MEX67. Interestingly, variation in VPS70 was recently identified as a QTL for ethanol tolerance in an industrial bio-ethanol strain. Taken together, our results show how, in contrast to adaptation to some other stresses, adaptation to a continuous complex and severe stress involves interplay of different evolutionary mechanisms. In addition, our study reveals functional modules involved in ethanol resistance and identifies several mutations that could help to improve the ethanol tolerance of industrial yeasts.

  1. Genetic and biochemical evidences reveal novel insights into the ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Biosciences; Volume 41; Issue 4. Genetic and biochemical evidences reveal novel insights into the mechanism underlying Saccharomyces cerevisiae Sae2-mediated abrogation of DNA replication stress. INDRAJEET GHODKE K MUNIYAPPA. ARTICLE Volume 41 Issue 4 December 2016 pp ...

  2. Mitochondrial and nuclear DNA reveals a complete lineage sorti ng ...

    African Journals Online (AJOL)

    Glossogobius callidus exhibits broad salinity tolerance and is distributed in both estuarine and freshwater environments in southern Africa. Previous studies revealed substantial morphological and molecular variation among populations, suggesting they constitute a species complex. The present study utilised phylogenetic ...

  3. Control rooms

    International Nuclear Information System (INIS)

    Preuss, W.

    1990-01-01

    The current state of knowledge about screen systems for application in traffic (e.g., flight control), process control, and production is presented. The 29 lectures, 5 of which relate to aviation, deal with the optimization of the man-machine interface with respect to unusual operating situations and adequate presentation and action methods on the basis of taks and event analyses integrating the users. (DG) [de

  4. Controlling Hypertension

    Centers for Disease Control (CDC) Podcasts

    Hypertension, or high blood pressure, affects one third of U.S. adults and is a leading cause of heart disease and stroke. A recent study found an increase in self-reported high blood pressure among U.S. adults, and an increase in the use of medications to control high blood pressure. In this podcast, Dr. Fleetwood Loustalot discusses the importance of controlling high blood pressure.

  5. Pathway-based outlier method reveals heterogeneous genomic structure of autism in blood transcriptome.

    Science.gov (United States)

    Campbell, Malcolm G; Kohane, Isaac S; Kong, Sek Won

    2013-09-24

    Decades of research strongly suggest that the genetic etiology of autism spectrum disorders (ASDs) is heterogeneous. However, most published studies focus on group differences between cases and controls. In contrast, we hypothesized that the heterogeneity of the disorder could be characterized by identifying pathways for which individuals are outliers rather than pathways representative of shared group differences of the ASD diagnosis. Two previously published blood gene expression data sets--the Translational Genetics Research Institute (TGen) dataset (70 cases and 60 unrelated controls) and the Simons Simplex Consortium (Simons) dataset (221 probands and 191 unaffected family members)--were analyzed. All individuals of each dataset were projected to biological pathways, and each sample's Mahalanobis distance from a pooled centroid was calculated to compare the number of case and control outliers for each pathway. Analysis of a set of blood gene expression profiles from 70 ASD and 60 unrelated controls revealed three pathways whose outliers were significantly overrepresented in the ASD cases: neuron development including axonogenesis and neurite development (29% of ASD, 3% of control), nitric oxide signaling (29%, 3%), and skeletal development (27%, 3%). Overall, 50% of cases and 8% of controls were outliers in one of these three pathways, which could not be identified using group comparison or gene-level outlier methods. In an independently collected data set consisting of 221 ASD and 191 unaffected family members, outliers in the neurogenesis pathway were heavily biased towards cases (20.8% of ASD, 12.0% of control). Interestingly, neurogenesis outliers were more common among unaffected family members (Simons) than unrelated controls (TGen), but the statistical significance of this effect was marginal (Chi squared P < 0.09). Unlike group difference approaches, our analysis identified the samples within the case and control groups that manifested each expression

  6. Three-cohort targeted gene screening reveals a non-synonymous TRKA polymorphism associated with schizophrenia

    DEFF Research Database (Denmark)

    van Schijndel, Jessica E; van Loo, Karen M J; van Zweeden, Martine

    2009-01-01

    selected non-synonymous single-nucleotide polymorphisms (SNPs) in three independent Caucasian schizophrenia case-control cohorts (USA, Denmark and Norway). A meta-analysis revealed ten non-synonymous SNPs that were nominally associated with schizophrenia, nine of which have not been previously linked...... attractive candidate for further study concerns SNP rs6336 (q=0.12) that causes the substitution of an evolutionarily highly conserved amino acid residue in the kinase domain of the neurodevelopmentally important receptor TRKA. Thus, TRKA signaling may represent a novel susceptibility pathway...

  7. Genome sequencing reveals metabolic and cellular interdependence in an amoeba-kinetoplastid symbiosis

    Czech Academy of Sciences Publication Activity Database

    Tanifuji, G.; Cenci, U.; Moog, D.; Dean, S.; Nakayama, T.; David, Vojtěch; Fiala, Ivan; Curtis, B.A.; Sibbald, S. J.; Onodera, N. T.; Colp, M.; Flegontov, Pavel; Johnson-MacKinnon, J.; McPhee, M.; Inagaki, Y.; Hashimoto, T.; Kelly, S.; Gull, K.; Lukeš, Julius; Archibald, J.M.

    2017-01-01

    Roč. 7, SEP 15 (2017), č. článku 11688. ISSN 2045-2322 R&D Projects: GA ČR(CZ) GA14-23986S; GA MŠk LL1601 Institutional support: RVO:60077344 Keywords : trypanosoma-brucei reveals * hidden markov model * neoparamoeba-pemaquidensis * gill disease * phylogenetic analyses * ichthyobodo-necator * gene prediction * host control * evolution * proteomics Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 4.259, year: 2016

  8. GABAB Receptor Constituents Revealed by Tandem Affinity Purification from Transgenic Mice

    DEFF Research Database (Denmark)

    Bartoi, Tudor; Rigbolt, Kristoffer T G; Du, Dan

    2010-01-01

    lines that allow a straightforward biochemical isolation of GABA(B) receptors. The transgenic mice express GABA(B1) isoforms that contain sequences for a two-step affinity purification, in addition to their endogenous subunit repertoire. Comparative analyses of purified samples from the transgenic mice...... and wild-type control animals revealed two novel components of the GABA(B1) complex. One of the identified proteins, potassium channel tetramerization domain-containing protein 12, associates with heterodimeric GABA(B) receptors via the GABA(B2) subunit. In transfected hippocampal neurons, potassium...

  9. Human iPSC Glial Mouse Chimeras Reveal Glial Contributions to Schizophrenia

    DEFF Research Database (Denmark)

    Windrem, Martha S.; Osipovitch, Mikhail; Liu, Zhengshan

    2017-01-01

    with childhood-onset SCZ. After neonatal implantation into myelin-deficient shiverer mice, SCZ GPCs showed premature migration into the cortex, leading to reduced white matter expansion and hypomyelination relative to controls. The SCZ glial chimeras also showed delayed astrocytic differentiation and abnormal...... astrocytic morphologies. When established in myelin wild-type hosts, SCZ glial mice showed reduced prepulse inhibition and abnormal behavior, including excessive anxiety, antisocial traits, and disturbed sleep. RNA-seq of cultured SCZ human glial progenitor cells (hGPCs) revealed disrupted glial...

  10. Baseline Evaluations to Support Control Room Modernization at Nuclear Power Plants

    Energy Technology Data Exchange (ETDEWEB)

    Boring, Ronald L.; Joe, Jeffrey C.

    2015-02-01

    For any major control room modernization activity at a commercial nuclear power plant (NPP) in the U.S., a utility should carefully follow the four phases prescribed by the U.S. Nuclear Regulatory Commission in NUREG-0711, Human Factors Engineering Program Review Model. These four phases include Planning and Analysis, Design, Verification and Validation, and Implementation and Operation. While NUREG-0711 is a useful guideline, it is written primarily from the perspective of regulatory review, and it therefore does not provide a nuanced account of many of the steps the utility might undertake as part of control room modernization. The guideline is largely summative—intended to catalog final products—rather than formative—intended to guide the overall modernization process. In this paper, we highlight two crucial formative sub-elements of the Planning and Analysis phase specific to control room modernization that are not covered in NUREG-0711. These two sub-elements are the usability and ergonomics baseline evaluations. A baseline evaluation entails evaluating the system as-built and currently in use. The usability baseline evaluation provides key insights into operator performance using the control system currently in place. The ergonomics baseline evaluation identifies possible deficiencies in the physical configuration of the control system. Both baseline evaluations feed into the design of the replacement system and subsequent summative benchmarking activities that help ensure that control room modernization represents a successful evolution of the control system.

  11. Baseline Evaluations to Support Control Room Modernization at Nuclear Power Plants

    International Nuclear Information System (INIS)

    Boring, Ronald L.; Joe, Jeffrey C.

    2015-01-01

    For any major control room modernization activity at a commercial nuclear power plant (NPP) in the U.S., a utility should carefully follow the four phases prescribed by the U.S. Nuclear Regulatory Commission in NUREG-0711, Human Factors Engineering Program Review Model. These four phases include Planning and Analysis, Design, Verification and Validation, and Implementation and Operation. While NUREG-0711 is a useful guideline, it is written primarily from the perspective of regulatory review, and it therefore does not provide a nuanced account of many of the steps the utility might undertake as part of control room modernization. The guideline is largely summative–intended to catalog final products–rather than formative–intended to guide the overall modernization process. In this paper, we highlight two crucial formative sub-elements of the Planning and Analysis phase specific to control room modernization that are not covered in NUREG-0711. These two sub-elements are the usability and ergonomics baseline evaluations. A baseline evaluation entails evaluating the system as-built and currently in use. The usability baseline evaluation provides key insights into operator performance using the control system currently in place. The ergonomics baseline evaluation identifies possible deficiencies in the physical configuration of the control system. Both baseline evaluations feed into the design of the replacement system and subsequent summative benchmarking activities that help ensure that control room modernization represents a successful evolution of the control system.

  12. Quantum control for initiation and detection of explosives

    International Nuclear Information System (INIS)

    Greenfield, Margo T.; McGrane, Shawn D.; Scharff, R. Jason; Moore, David S.

    2010-01-01

    We employ quantum control methods towards detection and quantum controlled initiation (QCI) of energetic materials. Ultrafast pulse shaping of broadband Infrared (∼750 nm to 850 run) and ultraviolet (266 nm, 400 nm) light is utilized for control. The underlying principals behind optimal control can be utilized to both detect and initiate explosives. In each case, time dependent phase shaped electric fields drive the chemical systems towards a desired state. For optimal dynamic detection of explosives (ODD-Ex) a phase specific broadband infrared pulse is created which increases not only the sensitivity of detection but also the selectivity of an explosive's spectral signatures in a background of interferents. QCI on the other hand, seeks to initiate explosives by employing shaped ultraviolet light. QCI is ideal for use with explosive detonators as it removes the possibility of unintentional initiation from an electrical source while adding an additional safety feature, initiation only with the proper pulse shape. Quantum control experiments require: (1) the ability to phase and amplitude shape the laser pulse and (2) the ability to effectively search for the pulse shape which controls the reaction. In these adaptive experiments we utilize both global and local optimization search routines such as genetic algorithm, differential evolution, and downhill simplex. Pulse shaping the broadband IR light, produced by focusing 800 nm light through a pressurized tube of Argon, is straightforward as commercial pulse shapers are available at and around 800 nm. Pulse shaping in the UV requires a home built shaper. Our system is an acoustic optical modulator (AOM) pulse shaper in which consists of a fused silica AOM crystal placed in the Fourier plane of a 4-f zero dispersion compressor.

  13. Control rods

    International Nuclear Information System (INIS)

    Koga, Isao; Masuoka, Ryuzo.

    1979-01-01

    Purpose: To prevent fuel element failures during power conditioning by removing liquid absorbents in poison tubes of control rods in a fast power up step and extracting control rods to slightly increase power in a medium power up step. Constitution: A plurality of poison tubes are disposed in a coaxial or plate-like arrangement and divided into a region capable of compensating the reactivity from the initial state at low temperature to 40% power operation and a region capable of compensating the reactivity in the power up above 40% power operation. Soluble poisons are used as absorbers in the poison tubes corresponding to above 40% power operation and they are adapted to be removed independently from the driving of control rods. The poison tubes filled with the soluble absorbers are responsible for the changes in the reactivity from the initial state at low temperature to the medium power region and the reactivity control is conducted by the elimination of liquid absorbers from the poison tubes. In the succeeding slight power up region above the medium power, power up is proceeding by extracting the control rods having remaining poison tubes filled with solid or liquid absorbers. (Seki, T.)

  14. Controlling percolation with limited resources

    Science.gov (United States)

    Schröder, Malte; Araújo, Nuno A. M.; Sornette, Didier; Nagler, Jan

    2017-12-01

    Connectivity, or the lack thereof, is crucial for the function of many man-made systems, from financial and economic networks over epidemic spreading in social networks to technical infrastructure. Often, connections are deliberately established or removed to induce, maintain, or destroy global connectivity. Thus, there has been a great interest in understanding how to control percolation, the transition to large-scale connectivity. Previous work, however, studied control strategies assuming unlimited resources. Here, we depart from this unrealistic assumption and consider the effect of limited resources on the effectiveness of control. We show that, even for scarce resources, percolation can be controlled with an efficient intervention strategy. We derive such an efficient strategy and study its implications, revealing a discontinuous transition as an unintended side effect of optimal control.

  15. Timing and motor control in drumming

    DEFF Research Database (Denmark)

    Dahl, Sofia; Grossbach, Michael; Altenmüller, Eckart

    the stick movement becomes increasingly difficult, sometimes resulting in irregularities in timing and/or striking force. Timing irregularities can also be a revealing sign of motor control problems, such as focal dystonia (Jabusch, Vauth & Altenmüller, 2004). The "breakdown" in motor control can therefore...

  16. Cosmic "Dig" Reveals Vestiges of the Milky Way's Building Blocks

    Science.gov (United States)

    2009-11-01

    Peering through the thick dust clouds of our galaxy's "bulge" (the myriads of stars surrounding its centre), and revealing an amazing amount of detail, a team of astronomers has unveiled an unusual mix of stars in the stellar grouping known as Terzan 5. Never observed anywhere in the bulge before, this peculiar "cocktail" of stars suggests that Terzan 5 is in fact one of the bulge's primordial building blocks, most likely the relic of a proto-galaxy that merged with the Milky Way during its very early days. "The history of the Milky Way is encoded in its oldest fragments, globular clusters and other systems of stars that have witnessed the entire evolution of our galaxy," says Francesco Ferraro from the University of Bologna, lead author of a paper appearing in this week's issue of the journal Nature. "Our study opens a new window on yet another piece of our galactic past." Like archaeologists, who dig through the dust piling up on top of the remains of past civilisations and unearth crucial pieces of the history of mankind, astronomers have been gazing through the thick layers of interstellar dust obscuring the bulge of the Milky Way and have unveiled an extraordinary cosmic relic. The target of the study is the star cluster Terzan 5. The new observations show that this object, unlike all but a few exceptional globular clusters, does not harbour stars which are all born at the same time - what astronomers call a "single population" of stars. Instead, the multitude of glowing stars in Terzan 5 formed in at least two different epochs, the earliest probably some 12 billion years ago and then again 6 billion years ago. "Only one globular cluster with such a complex history of star formation has been observed in the halo of the Milky Way: Omega Centauri," says team member Emanuele Dalessandro. "This is the first time we see this in the bulge." The galactic bulge is the most inaccessible region of our galaxy for astronomical observations: only infrared light can

  17. Losing control

    DEFF Research Database (Denmark)

    Leppink, Eric; Odlaug, Brian Lawrence; Lust, Katherine

    2014-01-01

    picking disorder). CONCLUSIONS: Assaultive behavior appears fairly common among college students and is associated with symptoms of depression and impulse control disorders. Significant distress and diminished behavioral control suggest that assaultive behaviors may often be associated with significant......OBJECTIVE: Assaultive behaviors are common among young people and have been associated with a range of other unhealthy, impulsive behaviors such as substance use and problem gambling. This study sought to determine the predictive ability of single assaultive incidents for impulse control disorders......, an association that has yet to be examined, especially in young adults. METHODS: The authors conducted a university-wide email survey in the spring of 2011 on 6000 university students. The survey examined assaultive behavior and associated mental health variables (using a clinically validated screening...

  18. NMR-Based Metabonomic Investigation of Heat Stress in Myotubes Reveals a Time-Dependent Change in the Metabolites

    DEFF Research Database (Denmark)

    Straadt, Ida K; Young, Jette F; Bross, Peter

    2010-01-01

    NMR-based metabonomics was applied to elucidate the time-dependent stress responses in mouse myotubes after heat exposure of either 42 or 45 degrees C for 1 h. Principal component analysis (PCA) revealed that the gradual time-dependent changes in metabolites contributing to the clustering...... and separation of the control samples from the different time points after heat stress primarily are in the metabolites glucose, leucine, lysine, phenylalanine, creatine, glutamine, and acetate. In addition, PC scores revealed a maximum change in metabolite composition 4 h after the stress exposure; thereafter......, samples returned toward control samples, however, without reaching the control samples even 10 h after stress. The results also indicate that the myotubes efficiently regulate the pH level by release of lactate to the culture medium at a heat stress level of 42 degrees C, which is a temperature level...

  19. Intracranial Hemorrhage Revealing Pseudohypoparathyroidism as a Cause of Fahr Syndrome

    Directory of Open Access Journals (Sweden)

    Abhijit Swami

    2011-01-01

    Full Text Available Pseudohypoparathyroidism is an infrequently encountered disease. It is one of the causes of Fahr syndrome which also is a rare clinical entity caused by multiple diseases. A 4-year-old man hospitalized for sudden onset left hemiparesis and hypertension was diagnosed to have right thalamic and midbrain hemorrhage on plain CT scan of the head which also revealed co-existent extensive intracranial calcifications involving the basal ganglia and cerebellum bilaterally. General physical examination revealed features of Albright hereditary osteodystrophy, goitre, hypertension, left hemiparesis, and signs of cerebellar dysfunction. Laboratory findings suggested hypocalcemia, hyperphosphatemia along with high TSH, low FT4, low FT3, and high anti-TPO antibody. Though bilateral intracranial calcifications are usually encountered as an incidental radiological finding in the CT scan of brain, in this case, the patient admitted for thalamic and midbrain hemorrhage was on investigation for associated intracranial calcification, and goitre was also found to have coexisting pseudohypoparathyroidism and autoimmune hypothyroidism.

  20. Tax Policy Trends: Republicans Reveal Proposed Tax Overhaul

    Directory of Open Access Journals (Sweden)

    Philip Bazel

    2017-10-01

    Full Text Available REPUBLICANS REVEAL PROPOSED TAX OVERHAUL The White House and Congressional Republicans have revealed their much-anticipated proposal for reform of the U.S. personal and corporate tax systems. The proposal titled, “UNIFIED FRAMEWORK FOR FIXING OUR BROKEN TAX CODE” outlines a number of central policy changes, which will significantly alter the U.S. corporate tax system. The proposal includes a top federal marginal rate reduction for the sole proprietorships, partnerships and S corporation—small business equivalents— from 39.6% to 25% (state income tax rates would no longer be deductible. Large corporations would also see a meaningful federal rate reduction given the proposed drop in the federal corporate income tax rate from 35% to 20%. Additionally, the proposal includes a generous temporary measure intended to stimulate investment, full capital expensing for machinery with a partial limitation of interest deductions.

  1. Obscure pulmonary masses: bronchial impaction revealed by CT

    International Nuclear Information System (INIS)

    Pugatch, R.D.; Gale, M.E.

    1983-01-01

    Dilated bronchi impacted with mucus or tumor are recognized on standard chest radiographs because they are surrounded by aerated pulmonary parenchyma. When imaged in different projections, these lesions produce a variety of appearances that are generally familiar. This report characterizes less familiar computed tomographic (CT) findings in eight patients with pathologic bronchial distension of congenital, neoplastic, or infectious etiologies and correlates them with chest films. In seven patients, CT readily revealed dilated bronchi and/or regional lung hypodensity. In four of these cases, CT led to the initial suspicion of dilated bronchi. CT should be used early in the evaluation of atypical pulmonary mass lesions or to confirm suspected bronchial impaction because of the high probability it will reveal diagnostic features

  2. What proverb understanding reveals about how people think.

    Science.gov (United States)

    Gibbs, R W; Beitel, D

    1995-07-01

    The ability to understand proverbial sayings, such as a rolling stone gathers no moss, has been of great interest to researchers in many areas of psychology. Most psychologists assume that understanding the figurative meanings of proverbs requires various kinds of higher order cognitive abilities. The authors review the findings on proverb interpretation to examine the question of what proverb use and understanding reveals about the ways normal and dysfunctional individuals think. The widely held idea that failure to provide a figurative interpretation of a proverb necessarily reflects a deficit in specialized abstract thinking is rejected. Moreover, the ability to correctly explain what a proverb means does not necessarily imply that an individual can think abstractly. Various empirical evidence, nonetheless, suggests that the ability to understand many proverbs reveals the presence of metaphorical schemes that are ubiquitous in everyday thought.

  3. Acting without seeing: eye movements reveal visual processing without awareness.

    Science.gov (United States)

    Spering, Miriam; Carrasco, Marisa

    2015-04-01

    Visual perception and eye movements are considered to be tightly linked. Diverse fields, ranging from developmental psychology to computer science, utilize eye tracking to measure visual perception. However, this prevailing view has been challenged by recent behavioral studies. Here, we review converging evidence revealing dissociations between the contents of perceptual awareness and different types of eye movement. Such dissociations reveal situations in which eye movements are sensitive to particular visual features that fail to modulate perceptual reports. We also discuss neurophysiological, neuroimaging, and clinical studies supporting the role of subcortical pathways for visual processing without awareness. Our review links awareness to perceptual-eye movement dissociations and furthers our understanding of the brain pathways underlying vision and movement with and without awareness. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Coordinating controls

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1986-07-15

    While physics Laboratories are having to absorb cuts in resources, the machines they rely on are becoming more and more complex, requiring increasingly sophisticated systems. Rather than being a resourceful engineer or physicist able to timber together solutions in his 'backyard', the modern controls specialist has become a professional in his own right. Because of possible conflicts between increasing sophistication on one hand and scarcer resources on the other, there was felt a need for more contacts among controls specialists to exchange experiences, coordinate development and discuss 'family problems', away from meetings where the main interest is on experimental physics.

  5. Helicopter Controllability

    Science.gov (United States)

    1989-09-01

    106 3. Program CC Systems Technology, Inc. (STI) of Hawthorne, CA., develops and markets PC control system analysis and design software including...is marketed in Palo Alto, Ca., by Applied i and can be used for both linear and non- linear control system analysis. Using TUTSIM involves developing...gravity centroid ( ucg ) can be calculated as 112 n m pi - 2 zi acg n i (7-5) where pi = poles zi = zeroes n = number of poles m = number of zeroes If K

  6. Coordinating controls

    International Nuclear Information System (INIS)

    Anon.

    1986-01-01

    While physics Laboratories are having to absorb cuts in resources, the machines they rely on are becoming more and more complex, requiring increasingly sophisticated systems. Rather than being a resourceful engineer or physicist able to timber together solutions in his 'backyard', the modern controls specialist has become a professional in his own right. Because of possible conflicts between increasing sophistication on one hand and scarcer resources on the other, there was felt a need for more contacts among controls specialists to exchange experiences, coordinate development and discuss 'family problems', away from meetings where the main interest is on experimental physics

  7. Digital tissue and what it may reveal about the brain.

    Science.gov (United States)

    Morgan, Josh L; Lichtman, Jeff W

    2017-10-30

    Imaging as a means of scientific data storage has evolved rapidly over the past century from hand drawings, to photography, to digital images. Only recently can sufficiently large datasets be acquired, stored, and processed such that tissue digitization can actually reveal more than direct observation of tissue. One field where this transformation is occurring is connectomics: the mapping of neural connections in large volumes of digitized brain tissue.

  8. Focus Groups to Reveal Parents' Needs for Prenatal Education

    OpenAIRE

    Dumas, Louise

    2002-01-01

    Focus group interviews are a useful qualitative research technique to obtain data from small groups about their opinions, attitudes, and/or feelings on a given subject. This particular technique has been used in Western Quebec in order to reveal the opinions, needs, and feelings of health professionals and future parents concerning prenatal education. As part of the region's priorities for 2002, all future parents in this part of the province were to be offered prenatal, government-paid, comm...

  9. Parascapular mass revealing primary tuberculosis of the posterior arch

    Science.gov (United States)

    Arbault, Anais; Ornetti, Paul; Chevallier, Olivier; Avril, Julien; Pottecher, Pierre

    2016-01-01

    We report the case of a parascapular abscess revealing primary tuberculosis of the posterior arch in a 31-year-old man. Sectional imaging is essential in order to detect the different lesions of this atypical spinal tuberculosis as osteolysis of the posterior arch extendible to vertebral body, osteocondensation, epidural extension which is common in this location, and high specificity of a zygapophysial, costo-vertebral or transverse arthritis. PMID:27709081

  10. [Colonic duplication revealed by intestinal obstruction due to fecal impaction].

    Science.gov (United States)

    Azahouani, A; Hida, M; Benhaddou, H

    2015-12-01

    Colonic duplications are very rare in children. With rectal duplications, they are the rarest locations of alimentary tract duplications, most often diagnosed in the first years of life. We report an unusual case of colic duplication with fecal impaction in a 9-month-old boy revealed by intestinal obstruction. We discuss the main diagnostic and therapeutic aspects of this malformation. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  11. 'Big bang' of B-cell development revealed.

    Science.gov (United States)

    Murre, Cornelis

    2018-01-15

    Earlier studies have identified transcription factors that specify B-cell fate, but the underlying mechanisms remain to be revealed. Two new studies by Miyai and colleagues (pp. 112-126) and Li and colleagues (pp. 96-111) in this issue of Genes & Development provide new and unprecedented insights into the genetic and epigenetic mechanisms that establish B-cell identity. © 2018 Murre; Published by Cold Spring Harbor Laboratory Press.

  12. Multivoxel Patterns Reveal Functionally Differentiated Networks Underlying Auditory Feedback Processing of Speech

    DEFF Research Database (Denmark)

    Zheng, Zane Z.; Vicente-Grabovetsky, Alejandro; MacDonald, Ewen N.

    2013-01-01

    The everyday act of speaking involves the complex processes of speech motor control. An important component of control is monitoring, detection, and processing of errors when auditory feedback does not correspond to the intended motor gesture. Here we show, using fMRI and converging operations...... within a multivoxel pattern analysis framework, that this sensorimotor process is supported by functionally differentiated brain networks. During scanning, a real-time speech-tracking system was used to deliver two acoustically different types of distorted auditory feedback or unaltered feedback while...... human participants were vocalizing monosyllabic words, and to present the same auditory stimuli while participants were passively listening. Whole-brain analysis of neural-pattern similarity revealed three functional networks that were differentially sensitive to distorted auditory feedback during...

  13. Arterial spin labelling reveals prolonged arterial arrival time in idiopathic Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Sarah Al-Bachari

    2014-01-01

    A significant (p = 0.005 increase in whole brain averaged baseline AAT was observed in IPD participants (mean ± SD age 1532 ± 138 ms compared to controls (mean ± SD age 1335 ± 165 ms. Voxel-wise analysis revealed this to be widespread across the brain. However, there were no statistically significant differences in white matter lesion score, CBF, or CVR between patients and controls. Regional CBF, but not AAT, in the IPD group was found to correlate positively with Montreal cognitive assessment (MoCA scores. These findings provide further evidence of alterations in NVS in IPD.

  14. Brands and Inhibition: A Go/No-Go Task Reveals the Power of Brand Influence.

    Science.gov (United States)

    Peatfield, Nicholas; Caulfield, Joanne; Parkinson, John; Intriligator, James

    2015-01-01

    Whether selecting a candy in a shop or picking a digital camera online, there are usually many options from which consumers may choose. With such abundance, consumers must use a variety of cognitive, emotional, and heuristic means to filter out and inhibit some of their responses. Here we use brand logos within a Go/No-Go task to probe inhibitory control during the presentation of familiar and unfamiliar logos. The results showed no differences in response times or in commission errors (CE) between familiar and unfamiliar logos. However, participants demonstrated a generally more cautious attitude of responding to the familiar brands: they were significantly slower and less accurate at responding to these brands in the Go trials. These findings suggest that inhibitory control can be exercised quite effectively for familiar brands, but that when such inhibition fails, the potent appetitive nature of brands is revealed.

  15. Transient light-induced intracellular oxidation revealed by redox biosensor

    Energy Technology Data Exchange (ETDEWEB)

    Kolossov, Vladimir L., E-mail: viadimer@illinois.edu [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); Beaudoin, Jessica N. [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); Department of Animal Sciences, University of Illinois at Urbana-Champaign, 1207 W. Gregory Drive, Urbana, IL 61801 (United States); Hanafin, William P. [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); DiLiberto, Stephen J. [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); Department of Animal Sciences, University of Illinois at Urbana-Champaign, 1207 W. Gregory Drive, Urbana, IL 61801 (United States); Kenis, Paul J.A. [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 600 S. Mathews Avenue, Urbana, IL 61801 (United States); Rex Gaskins, H. [Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Drive, Urbana, IL 61801 (United States); Department of Animal Sciences, University of Illinois at Urbana-Champaign, 1207 W. Gregory Drive, Urbana, IL 61801 (United States); Department of Pathobiology, University of Illinois at Urbana-Champaign, 2001 S. Lincoln Avenue, Urbana, IL 61801 (United States); Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 905 S. Goodwin Avenue, Urbana, IL 61801 (United States)

    2013-10-04

    Highlights: •Time-resolved live cell imaging revealed light-induced oxidation. •Only the roGFP probe fused with glutaredoxin reveals photooxidation. •The transient oxidation is rapidly reduced by the cytosolic antioxidant system. •Intracellular photooxidation is media-dependent. •Oxidation is triggered exclusively by exposure to short wavelength excitation. -- Abstract: We have implemented a ratiometric, genetically encoded redox-sensitive green fluorescent protein fused to human glutaredoxin (Grx1-roGFP2) to monitor real time intracellular glutathione redox potentials of mammalian cells. This probe enabled detection of media-dependent oxidation of the cytosol triggered by short wavelength excitation. The transient nature of light-induced oxidation was revealed by time-lapse live cell imaging when time intervals of less than 30 s were implemented. In contrast, transient ROS generation was not observed with the parental roGFP2 probe without Grx1, which exhibits slower thiol-disulfide exchange. These data demonstrate that the enhanced sensitivity of the Grx1-roGFP2 fusion protein enables the detection of short-lived ROS in living cells. The superior sensitivity of Grx1-roGFP2, however, also enhances responsiveness to environmental cues introducing a greater likelihood of false positive results during image acquisition.

  16. Transient light-induced intracellular oxidation revealed by redox biosensor

    International Nuclear Information System (INIS)

    Kolossov, Vladimir L.; Beaudoin, Jessica N.; Hanafin, William P.; DiLiberto, Stephen J.; Kenis, Paul J.A.; Rex Gaskins, H.

    2013-01-01

    Highlights: •Time-resolved live cell imaging revealed light-induced oxidation. •Only the roGFP probe fused with glutaredoxin reveals photooxidation. •The transient oxidation is rapidly reduced by the cytosolic antioxidant system. •Intracellular photooxidation is media-dependent. •Oxidation is triggered exclusively by exposure to short wavelength excitation. -- Abstract: We have implemented a ratiometric, genetically encoded redox-sensitive green fluorescent protein fused to human glutaredoxin (Grx1-roGFP2) to monitor real time intracellular glutathione redox potentials of mammalian cells. This probe enabled detection of media-dependent oxidation of the cytosol triggered by short wavelength excitation. The transient nature of light-induced oxidation was revealed by time-lapse live cell imaging when time intervals of less than 30 s were implemented. In contrast, transient ROS generation was not observed with the parental roGFP2 probe without Grx1, which exhibits slower thiol-disulfide exchange. These data demonstrate that the enhanced sensitivity of the Grx1-roGFP2 fusion protein enables the detection of short-lived ROS in living cells. The superior sensitivity of Grx1-roGFP2, however, also enhances responsiveness to environmental cues introducing a greater likelihood of false positive results during image acquisition

  17. Cryogenic EBSD reveals structure of directionally solidified ice–polymer composite

    International Nuclear Information System (INIS)

    Donius, Amalie E.; Obbard, Rachel W.; Burger, Joan N.; Hunger, Philipp M.; Baker, Ian; Doherty, Roger D.; Wegst, Ulrike G.K.

    2014-01-01

    Despite considerable research efforts on directionally solidified or freeze-cast materials in recent years, little fundamental knowledge has been gained that links model with experiment. In this contribution, the cryogenic characterization of directionally solidified polymer solutions illustrates, how powerful cryo-scanning electron microscopy combined with electron backscatter diffraction is for the structural characterization of ice–polymer composite materials. Under controlled sublimation, the freeze-cast polymer scaffold structure is revealed and imaged with secondary electrons. Electron backscatter diffraction fabric analysis shows that the ice crystals, which template the polymer scaffold and create the lamellar structure, have a-axes oriented parallel to the direction of solidification and the c-axes perpendicular to it. These results indicate the great potential of both cryo-scanning electron microscopy and cryo-electron backscatter diffraction in gaining fundamental knowledge of structure–property–processing correlations. - Highlights: • Cryo-SEM of freeze-cast polymer solution reveals an ice-templated structure. • Cryo-EBSD reveals the ice crystal a-axis to parallel the solidification direction. • The honeycomb-like polymer phase favors columnar ridges only on one side. • Combining cryo-SEM with EBSD links solidification theory with experiment

  18. Cryogenic EBSD reveals structure of directionally solidified ice–polymer composite

    Energy Technology Data Exchange (ETDEWEB)

    Donius, Amalie E., E-mail: amalie.donius@gmail.com [Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755 (United States); Department of Materials Science and Engineering, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104 (United States); Obbard, Rachel W., E-mail: Rachel.W.Obbard@dartmouth.edu [Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755 (United States); Burger, Joan N., E-mail: ridge.of.the.ancients@gmail.com [Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755 (United States); Department of Materials Science and Engineering, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104 (United States); Hunger, Philipp M., E-mail: philipp.m.hunger@gmail.com [Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755 (United States); Department of Materials Science and Engineering, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104 (United States); Baker, Ian, E-mail: Ian.Baker@dartmouth.edu [Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755 (United States); Doherty, Roger D., E-mail: dohertrd@drexel.edu [Department of Materials Science and Engineering, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104 (United States); Wegst, Ulrike G.K., E-mail: ulrike.wegst@dartmouth.edu [Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755 (United States)

    2014-07-01

    Despite considerable research efforts on directionally solidified or freeze-cast materials in recent years, little fundamental knowledge has been gained that links model with experiment. In this contribution, the cryogenic characterization of directionally solidified polymer solutions illustrates, how powerful cryo-scanning electron microscopy combined with electron backscatter diffraction is for the structural characterization of ice–polymer composite materials. Under controlled sublimation, the freeze-cast polymer scaffold structure is revealed and imaged with secondary electrons. Electron backscatter diffraction fabric analysis shows that the ice crystals, which template the polymer scaffold and create the lamellar structure, have a-axes oriented parallel to the direction of solidification and the c-axes perpendicular to it. These results indicate the great potential of both cryo-scanning electron microscopy and cryo-electron backscatter diffraction in gaining fundamental knowledge of structure–property–processing correlations. - Highlights: • Cryo-SEM of freeze-cast polymer solution reveals an ice-templated structure. • Cryo-EBSD reveals the ice crystal a-axis to parallel the solidification direction. • The honeycomb-like polymer phase favors columnar ridges only on one side. • Combining cryo-SEM with EBSD links solidification theory with experiment.

  19. Dissecting a role for melanopsin in behavioural light aversion reveals a response independent of conventional photoreception.

    Directory of Open Access Journals (Sweden)

    Ma'ayan Semo

    Full Text Available Melanopsin photoreception plays a vital role in irradiance detection for non-image forming responses to light. However, little is known about the involvement of melanopsin in emotional processing of luminance. When confronted with a gradient in light, organisms exhibit spatial movements relative to this stimulus. In rodents, behavioural light aversion (BLA is a well-documented but poorly understood phenomenon during which animals attribute salience to light and remove themselves from it. Here, using genetically modified mice and an open field behavioural paradigm, we investigate the role of melanopsin in BLA. While wildtype (WT, melanopsin knockout (Opn4(-/- and rd/rd cl (melanopsin only (MO mice all exhibit BLA, our novel methodology reveals that isolated melanopsin photoreception produces a slow, potentiating response to light. In order to control for the involvement of pupillary constriction in BLA we eliminated this variable with topical atropine application. This manipulation enhanced BLA in WT and MO mice, but most remarkably, revealed light aversion in triple knockout (TKO mice, lacking three elements deemed essential for conventional photoreception (Opn4(-/- Gnat1(-/- Cnga3(-/-. Using a number of complementary strategies, we determined this response to be generated at the level of the retina. Our findings have significant implications for the understanding of how melanopsin signalling may modulate aversive responses to light in mice and humans. In addition, we also reveal a clear potential for light perception in TKO mice.

  20. Signalling pathways involved in adult heart formation revealed by gene expression profiling in Drosophila.

    Directory of Open Access Journals (Sweden)

    Bruno Zeitouni

    2007-10-01

    Full Text Available Drosophila provides a powerful system for defining the complex genetic programs that drive organogenesis. Under control of the steroid hormone ecdysone, the adult heart in Drosophila forms during metamorphosis by a remodelling of the larval cardiac organ. Here, we evaluated the extent to which transcriptional signatures revealed by genomic approaches can provide new insights into the molecular pathways that underlie heart organogenesis. Whole-genome expression profiling at eight successive time-points covering adult heart formation revealed a highly dynamic temporal map of gene expression through 13 transcript clusters with distinct expression kinetics. A functional atlas of the transcriptome profile strikingly points to the genomic transcriptional response of the ecdysone cascade, and a sharp regulation of key components belonging to a few evolutionarily conserved signalling pathways. A reverse genetic analysis provided evidence that these specific signalling pathways are involved in discrete steps of adult heart formation. In particular, the Wnt signalling pathway is shown to participate in inflow tract and cardiomyocyte differentiation, while activation of the PDGF-VEGF pathway is required for cardiac valve formation. Thus, a detailed temporal map of gene expression can reveal signalling pathways responsible for specific developmental programs and provides here substantial grasp into heart formation.

  1. Topology control

    NARCIS (Netherlands)

    Buchin, K.; Buchin, M.; Wagner, D.; Wattenhofer, R.

    2007-01-01

    Information between two nodes in a network is sent based on the network topology, the structure of links connecting pairs of nodes of a network. The task of topology control is to choose a connecting subset from all possible links such that the overall network performance is good. For instance, a

  2. Control mental

    OpenAIRE

    Bueno i Torrens, David, 1965-

    2013-01-01

    La revista especialitzada NeuroReport ha publicat un article que m'ha aportat nous elements de reflexió sobre els mecanismes neurals de control mental que, de forma innata, realitzem les persones com a part de la nostra vida social.

  3. Control rod

    International Nuclear Information System (INIS)

    Igarashi, Takao; Yoshimoto, Yuichiro; Sugawara, Satoshi; Fukumoto, Takashi; Endo, Zen-ichiro; Saito, Shozo; Shinpo, Katsutoshi; Nishimura, Akira; Ozawa, Michihiro

    1988-01-01

    Purpose: To provide a sufficient shutdown margin upon reactor shutdown, prevent sheath deformation without decreasing neutron absorbents and prevent impact shocks exerted to structural materials. Constitution: The control rod of the present invention comprises a neutron absorption region, a sheath deformation means attached to the side wall and means for restricting and supporting axial movement of the neutron absorbent rod. Then, the amount of absorptive nuclei chained absorbents in the lower region is reduced than that in the upper region. In this way, effective neutron absorbing performance can be obtained relative to the neutron importance distribution during reactor shutdown. In addition, since the operationability is improved by reducing the weight of the control rod and the absorptive nuclei chained neutron abosrbers are used, mechanical nuclear life of the control rod can be increased. Thus, it is possible to prevent the outward deformation of the sheath, as well as prevent collision between the neutron absorber rod and the structural material on the side of inserting the control rod generated upon reactor scram by a simple structure. (Kamimura, M.)

  4. Motions in Nearby Galaxy Cluster Reveal Presence of Hidden Superstructure

    Science.gov (United States)

    2004-09-01

    A nearby galaxy cluster is facing an intergalactic headwind as it is pulled by an underlying superstructure of dark matter, according to new evidence from NASA's Chandra X-ray Observatory. Astronomers think that most of the matter in the universe is concentrated in long large filaments of dark matter and that galaxy clusters are formed where these filaments intersect. A Chandra survey of the Fornax galaxy cluster revealed a vast, swept-back cloud of hot gas near the center of the cluster. This geometry indicates that the hot gas cloud, which is several hundred thousand light years in length, is moving rapidly through a larger, less dense cloud of gas. The motion of the core gas cloud, together with optical observations of a group of galaxies racing inward on a collision course with it, suggests that an unseen, large structure is collapsing and drawing everything toward a common center of gravity. X-ray Image of Fornax with labels X-ray Image of Fornax with labels "At a relatively nearby distance of about 60 million light years, the Fornax cluster represents a crucial laboratory for studying the interplay of galaxies, hot gas and dark matter as the cluster evolves." said Caleb Scharf of Columbia University in New York, NY, lead author of a paper describing the Chandra survey that was presented at an American Astronomical Society meeting in New Orleans, LA. "What we are seeing could be associated directly with the intergalactic gas surrounding a very large scale structure that stretches over millions of light years." The infalling galaxy group, whose motion was detected by Michael Drinkwater of the University of Melbourne in Australia, and colleagues, is about 3 million light years from the cluster core, so a collision with the core will not occur for a few billion years. Insight as to how this collision will look is provided by the elliptical galaxy NGC 1404 that is plunging into the core of the cluster for the first time. As discussed by Scharf and another group

  5. Mitochondrial DNA analysis reveals a low nucleotide diversity of ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-06-17

    Jun 17, 2009 ... gene sequences of C. japonica in China to assess nucleotide sequence diversity (GenBank ... provide a scientific basis for the regional control of forestry .... population (AB015869) was downloaded from GenBank database.

  6. A genetic analysis of segregation distortion revealed by molecular ...

    Indian Academy of Sciences (India)

    Journal of Genetics, Vol. 90, No. ... Segregation analysis was based on 64 molecular markers, including 26 .... FHB of RIL populations was controlled by quantitative trait ... The authors acknowledge financial support by the National Basic.

  7. COPD - control drugs

    Science.gov (United States)

    Chronic obstructive pulmonary disease - control drugs; Bronchodilators - COPD - control drugs; Beta agonist inhaler - COPD - control drugs; Anticholinergic inhaler - COPD - control drugs; Long-acting inhaler - COPD - control drugs; ...

  8. Revealing the functions of the transketolase enzyme isoforms in Rhodopseudomonas palustris using a systems biology approach.

    Directory of Open Access Journals (Sweden)

    Chia-Wei Hu

    Full Text Available BACKGROUND: Rhodopseudomonas palustris (R. palustris is a purple non-sulfur anoxygenic phototrophic bacterium that belongs to the class of proteobacteria. It is capable of absorbing atmospheric carbon dioxide and converting it to biomass via the process of photosynthesis and the Calvin-Benson-Bassham (CBB cycle. Transketolase is a key enzyme involved in the CBB cycle. Here, we reveal the functions of transketolase isoforms I and II in R. palustris using a systems biology approach. METHODOLOGY/PRINCIPAL FINDINGS: By measuring growth ability, we found that transketolase could enhance the autotrophic growth and biomass production of R. palustris. Microarray and real-time quantitative PCR revealed that transketolase isoforms I and II were involved in different carbon metabolic pathways. In addition, immunogold staining demonstrated that the two transketolase isoforms had different spatial localizations: transketolase I was primarily associated with the intracytoplasmic membrane (ICM but transketolase II was mostly distributed in the cytoplasm. Comparative proteomic analysis and network construction of transketolase over-expression and negative control (NC strains revealed that protein folding, transcriptional regulation, amino acid transport and CBB cycle-associated carbon metabolism were enriched in the transketolase I over-expressed strain. In contrast, ATP synthesis, carbohydrate transport, glycolysis-associated carbon metabolism and CBB cycle-associated carbon metabolism were enriched in the transketolase II over-expressed strain. Furthermore, ATP synthesis assays showed a significant increase in ATP synthesis in the transketolase II over-expressed strain. A PEPCK activity assay showed that PEPCK activity was higher in transketolase over-expressed strains than in the negative control strain. CONCLUSIONS/SIGNIFICANCE: Taken together, our results indicate that the two isoforms of transketolase in R. palustris could affect photoautotrophic growth

  9. Genome-wide analysis reveals the vacuolar pH-stat of Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Christopher L Brett

    Full Text Available Protons, the smallest and most ubiquitous of ions, are central to physiological processes. Transmembrane proton gradients drive ATP synthesis, metabolite transport, receptor recycling and vesicle trafficking, while compartmental pH controls enzyme function. Despite this fundamental importance, the mechanisms underlying pH homeostasis are not entirely accounted for in any organelle or organism. We undertook a genome-wide survey of vacuole pH (pH(v in 4,606 single-gene deletion mutants of Saccharomyces cerevisiae under control, acid and alkali stress conditions to reveal the vacuolar pH-stat. Median pH(v (5.27±0.13 was resistant to acid stress (5.28±0.14 but shifted significantly in response to alkali stress (5.83±0.13. Of 107 mutants that displayed aberrant pH(v under more than one external pH condition, functional categories of transporters, membrane biogenesis and trafficking machinery were significantly enriched. Phospholipid flippases, encoded by the family of P4-type ATPases, emerged as pH regulators, as did the yeast ortholog of Niemann Pick Type C protein, implicated in sterol trafficking. An independent genetic screen revealed that correction of pH(v dysregulation in a neo1(ts mutant restored viability whereas cholesterol accumulation in human NPC1(-/- fibroblasts diminished upon treatment with a proton ionophore. Furthermore, while it is established that lumenal pH affects trafficking, this study revealed a reciprocal link with many mutants defective in anterograde pathways being hyperacidic and retrograde pathway mutants with alkaline vacuoles. In these and other examples, pH perturbations emerge as a hitherto unrecognized phenotype that may contribute to the cellular basis of disease and offer potential therapeutic intervention through pH modulation.

  10. Environmental controls

    International Nuclear Information System (INIS)

    Brown, S.

    1996-01-01

    Members of the public are exposed to environmental radiations from a variety of sources. In terms of average dose received the major component is from natural sources of radiation for which there is little or no scope to reduce exposure. Where such opportunities do exist, in those homes with high radon concentrations, the householders tend to ignore the risks despite the availability of comparatively straightforward and inexpensive remediation measures. By comparison there is significant public concern about radioactive waste management and the disposal and discharge of radioactivity to the environment despite strict environmental controls. This paper describes the controls and the wider policy context for radioactive waste management following a major review of policy last year. (author)

  11. Controllable dose

    International Nuclear Information System (INIS)

    Alvarez R, J.T.; Anaya M, R.A.

    2004-01-01

    With the purpose of eliminating the controversy about the lineal hypothesis without threshold which found the systems of dose limitation of the recommendations of ICRP 26 and 60, at the end of last decade R. Clarke president of the ICRP proposed the concept of Controllable Dose: as the dose or dose sum that an individual receives from a particular source which can be reasonably controllable by means of any means; said concept proposes a change in the philosophy of the radiological protection of its concern by social approaches to an individual focus. In this work a panorama of the foundations is presented, convenient and inconveniences that this proposal has loosened in the international community of the radiological protection, with the purpose of to familiarize to our Mexican community in radiological protection with these new concepts. (Author)

  12. quality control

    International Nuclear Information System (INIS)

    Skujina, A.; Purina, S.; Riekstina, D.

    1999-01-01

    The optimal objects: soils, spruce needles and bracken ferns were found for the environmental monitoring in the regions of possible radioactive contamination - near SalaspiIs nuclear reactor and Ignalina nuclear power plant. The determination of Sr-90 was based on the radiochemical separation of Sr-90 (=Y-90) by HDEHP extraction and counting the Cerenkov radiation. The quality control of the results was carried out. (authors)

  13. Vehicle Controller

    Science.gov (United States)

    1985-01-01

    UNISTICK is an airplane-like joystick being developed by Johnson Engineering under NASA and VA sponsorship. It allows a driver to control a vehicle with one hand, and is based upon technology developed for the Apollo Lunar Landings of the 1970's. It allows severely handicapped drivers to operate an automobile or van easily. The system is expected to be in production by March 1986.

  14. Revealed Comparative Advantage of Services in Cariforum Countries

    Directory of Open Access Journals (Sweden)

    Marie Freckleton

    2014-09-01

    Full Text Available A pesar de la importancia de las exportaciones de servicios a los países del CARIFORUM no hay muchos estudios sobre de la competitividad de las exportaciones. Este artículo examina la ventaja comparativa revelada de las exportaciones de servicios de los países del CARIFORUM. El análisis muestra que la mayoría de los países del CARIFORUM han puesto de manifiesto las ventajas comparativas en el turismo, pero también hay casos de ventaja comparativa revelada en otros servicios como transporte, seguros y servicios empresariales, servicios personales, culturales y recreativos. Los resultados sugieren que existe un potencial de CARIFORUM para diversificar las exportaciones de servicios con el fin de pro-mover el crecimiento económico y reducir la vulnerabilidad. Sin embargo, en la medida en que los países del CARIFORUM pueden tomar ventaja de las oportunidades existentes de acceso al Mercado de los servicios depende de su capacidad de mejorar la capacidad de oferta de servicios y promover la competitividad de los servicios. English: Despite the importance of services ex-ports to CARIFORUM countries there is limited research on the competitiveness of such exports. This article examines the revealed comparative advantage of services exports in CARIFORUM countries. The analysis shows that most CARIFORUM countries have revealed comparative advantage in tourism but there are also cases of revealed comparative advantage in other services including transport, insurance, business services and personal, cultural and recreational services. The results suggest that there is potential for CARIFORUM to diversify exports of services in order to promote economic growth and reduce vulnerability. However, the extent to which CARIFORUM countries can take advantage of existing market access opportunities for services depends on their ability to improve the capacity to supply services and to promote the competitiveness of services.

  15. Genes but not genomes reveal bacterial domestication of Lactococcus lactis.

    Directory of Open Access Journals (Sweden)

    Delphine Passerini

    Full Text Available BACKGROUND: The population structure and diversity of Lactococcus lactis subsp. lactis, a major industrial bacterium involved in milk fermentation, was determined at both gene and genome level. Seventy-six lactococcal isolates of various origins were studied by different genotyping methods and thirty-six strains displaying unique macrorestriction fingerprints were analyzed by a new multilocus sequence typing (MLST scheme. This gene-based analysis was compared to genomic characteristics determined by pulsed-field gel electrophoresis (PFGE. METHODOLOGY/PRINCIPAL FINDINGS: The MLST analysis revealed that L. lactis subsp. lactis is essentially clonal with infrequent intra- and intergenic recombination; also, despite its taxonomical classification as a subspecies, it displays a genetic diversity as substantial as that within several other bacterial species. Genome-based analysis revealed a genome size variability of 20%, a value typical of bacteria inhabiting different ecological niches, and that suggests a large pan-genome for this subspecies. However, the genomic characteristics (macrorestriction pattern, genome or chromosome size, plasmid content did not correlate to the MLST-based phylogeny, with strains from the same sequence type (ST differing by up to 230 kb in genome size. CONCLUSION/SIGNIFICANCE: The gene-based phylogeny was not fully consistent with the traditional classification into dairy and non-dairy strains but supported a new classification based on ecological separation between "environmental" strains, the main contributors to the genetic diversity within the subspecies, and "domesticated" strains, subject to recent genetic bottlenecks. Comparison between gene- and genome-based analyses revealed little relationship between core and dispensable genome phylogenies, indicating that clonal diversification and phenotypic variability of the "domesticated" strains essentially arose through substantial genomic flux within the dispensable

  16. Control rod

    International Nuclear Information System (INIS)

    Takeda, Toshikazu; Inoue, Kotaro.

    1979-01-01

    Purpose: To flatten the power distribution in the reactor core without impairing neutron economy by disposing pins containing elements of lower atomic number in the central region of a shroud and loading pins containing depleted uranium in the periphery region thereof. Constitution: The shroud has a layer of pins containing depleted uranium in the peripheral region and a layer of pins containing elements of lower atomic number such as beryllium in the central region. Heat removal from those pins containing depleted uranium and elements of lower atomic number (neutron moderator) is effected by sodium flow outside of the cladding material. The control rod operation is conducted by inserting or extracting the central portion (pins containing elements of lower atomic number such as beryllium) inside of the stainless pipe. Upon extraction of the control rod, the moderator in the central region is removed whereby high speed neutrons are no more deccelerated and the absorption rate to the depleted uranium is decreased. This can flatten the power distribution in the reactore core with the disposition of a plurality of control rods at a better neutron economy as compared with the use of neutron absorber such as boron. (Seki, T.)

  17. Control rod

    International Nuclear Information System (INIS)

    Fukumoto, Takashi; Hirakawa, Hiromasa; Kawashima, Norio; Goto, Yasuyuki.

    1994-01-01

    Neutron absorbers are contained in a tubular member comprising, integrally a tubular portion and four corners disposed at the outer circumference of the tubular portion at every 90deg, to provide a neutron absorbing tube. A plurality of neutron absorbing tubes are arranged in parallel in the lateral direction, and adjacent corners are joined, into a blade to constitute a control rod. Such a control rod has a great structural strength, simple in the structure and relatively light in weight and can contain a great amount of neutron absorbers. Upon formation of the control rod by arranging the blades in a cross-like shape, at least a portion thereof is constituted with short neutron absorbing tubes shorter than the entire length of the blade, and gaps are formed at positions in adjacent in the axial direction. With such a constitution, there is no worry that a wing end of the blade collides against or be abraded with a fuel channel box or a fuel support. Even if fuel channels are vibrated upon scram of the reactor, such as occurrence of earthquakes, it can be inserted to the reactor easily. (N.H.)

  18. Controlled fragmentation

    International Nuclear Information System (INIS)

    Arnold, Werner

    2002-01-01

    Contrary to natural fragmentation, controlled fragmentation offers the possibility to adapt fragment parameters like size and mass to the performance requirements in a very flexible way. Known mechanisms like grooves inside the casing, weaken the structure. This is, however, excluded for applications with high accelerations during launch or piercing requirements for example on a semi armor piercing penetrator. Another method to achieve controlled fragmentation with an additional grid layer is presented with which the required grooves are produced 'just in time' inside the casing during detonation of the high explosive. The process of generating the grooves aided by the grid layer was studied using the hydrocode HULL with respect to varying grid designs and material combinations. Subsequent to this, a large range of these theoretically investigated combinations was contemplated in substantial experimental tests. With an optimised grid design and a suitable material selection, the controlled fragment admits a very flexible adaptation to the set requirements. Additional advantages like the increase of perforation performance or incendiary amplification can be realized with the grid layer

  19. Malar Bone Metastasis Revealing a Papillary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Ihsen Slim

    2012-01-01

    Full Text Available Papillary thyroid carcinoma is the most common form of differentiated thyroid carcinoma. It is generally confined to the neck with or without spread to regional lymph nodes. Metastatic thyroid carcinomas are uncommon and mainly include lung and bone. Metastases involving oral and maxillofacial region are extremely rare. We described a case of malar metastasis revealing a follicular variant of papillary thyroid carcinoma, presenting with pain and swelling of the left cheek in a 67-years-old female patient with an unspecified histological left lobo-isthmectomy medical history. To our knowledge, this is the first recorded instance of a malar metastasis from a follicular variant of papillary thyroid carcinoma.

  20. [Neonatal adrenal hemorrhage revealed by jaundice: a case report].

    Science.gov (United States)

    Oulmaati, A; Hays, S; Mory-Thomas, N; Bretones, P; Bensaid, M; Jordan, I; Bonfils, M; Godbert, I; Picaud, J-C

    2012-04-01

    The clinical presentation of adrenal hemorrhage varies, depending on the extent of hemorrhage as well as the amount of adrenal cortex involved by the hemorrhage. We report here a case of neonatal adrenal hemorrhage revealed by late onset of neonatal jaundice. This adrenal hemorrhage most probably resulted from shoulder dystocia. The aim of this work was to focus on the fact that jaundice can be caused by adrenal hemorrhage and to emphasize the crucial importance of abdominal ultrasound in cases of persistent jaundice. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  1. A Solitary Fibrous Tumor of the Pleura Revealed by Hiccups

    Directory of Open Access Journals (Sweden)

    A. Chafik

    2011-01-01

    Full Text Available Solitary fibrous tumors of the pleura are rare and benign primary localized tumors; they possess a malignant potential and thus should be excised. We report a case of a 43-year-old woman, who had suffered for 5 years from right basithoracic pain associated with progressive dyspnea and persistent hiccups during the last 6 months. We have not found any similar case in the literature. Further testing after excision by thoracotomy revealed a solitary fibrous pleural tumor. A brief discussion of the clinical presentation and incidence of these tumors is included.

  2. [Suicide -- an essay trying to reveal the theme].

    Science.gov (United States)

    Sampaio, M A; Boemer, M R

    2000-12-01

    This essay proposes to reveal facets of the suicide through the discourse of different authors treating this theme as well as through contacts that I was able to have in my nursing training, through my academic trajectory. This trajectory includes an incursion by phenomenological ideas, mainly by the ideas of Heidegger and his existential analysis of the man as being-there. In this way, the understanding of a person who decides to finalize his/her existence, can be, by the existential analysis perspective, a way to reconstruct and redimension his/her existential perspectives.

  3. Windows PowerShell desired state configuration revealed

    CERN Document Server

    Chaganti, Ravikanth

    2014-01-01

    Desired State Configuration (DSC) is a powerful new configuration management platform that makes it easier than ever to perform cross-platform configuration management of your infrastructure, whether on-premise or in the cloud. DSC provides the management platform and Application Programming Interface (API) that can be used with any programming language. Windows PowerShell Desired State Configuration Revealed will take you through this new technology from start to finish and demonstrates the DSC interfaces through Windows PowerShell. DSC allows you to manage target devices by simply declarin

  4. Platinum(IV) complex LA-12 induces cell cycle phase specific apoptosis in colon carcinoma cell line HCT-116

    Czech Academy of Sciences Publication Activity Database

    Vondálová Blanářová, Olga; Jelínková, Iva; Jendželovský, R.; Souček, Karel; Hofmanová, Jiřina; Sova, P.; Kozubík, Alois

    2009-01-01

    Roč. 276, č. 1 (2009), s. 256-257 ISSN 1742-464X. [34th FEBS Congress. 04.07.2009-09.07.2009, Prague] R&D Projects: GA AV ČR(CZ) 1QS500040507; GA ČR(CZ) GA301/07/1557 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : platinum drugs * cell cycle apoptosis Subject RIV: BO - Biophysics

  5. Relationship between antigravity control and postural control in young children.

    Science.gov (United States)

    Sellers, J S

    1988-04-01

    The purposes of this study were 1) to determine the relationship between antigravity control (supine flexion and prone extension) and postural control (static and dynamic balance), 2) to determine the quality of antigravity and postural control, and 3) to determine whether sex and ethnic group differences correlate with differences in antigravity control and postural control in young children. I tested 107 black, Hispanic, and Caucasian children in a Head Start program, with a mean age of 61 months. The study results showed significant relationships between antigravity control and postural control. Subjects' supine flexion performance was significantly related to the quantity and quality of their static and dynamic balance performance, whereas prone extension performance was related only to the quality of dynamic balance performance. Quality scale measurements (r = .90) indicated that the children in this study had not yet developed full antigravity or postural control. The study results revealed differences between sexes in the quality of static balance and prone extension performance and ethnic differences in static balance, dynamic balance, and prone extension performance.

  6. FINANCIAL CONTROL AS A CATEGORY

    Directory of Open Access Journals (Sweden)

    Andrey Yu. Volkov

    2014-01-01

    Full Text Available The article reveals the basics of “financial control” as a category. The main attention is concentrated on the “control” itself (asa term, multiplicity of interpretation of“financial control” term and its juristic-practical matching. The duality of financial control category is detected. The identity of terms “financial control” and “state financial control” is justified. The article also offers ways of development of financial control juristical regulation.

  7. Tremendous Mass Concentration in Strange Galaxy Revealed by VLBA

    Science.gov (United States)

    1995-01-01

    A dense whirling mass orbiting what almost certainly is a black hole of truly Brobdingnagian proportions has been discovered at the heart of an active galaxy some 21 million light years from Earth. The astronomical observations were made by an international team of Japanese and American astronomers using a continent-wide radio telescope funded by the National Science Foundation. The work is reported in the January 12th issue of Nature. The tremendous concentration of mass, equivalent to 40 million suns, in the center of the galaxy NGC4258 in the constellation Canes Venatici, was revealed by the apparent rotation of a molecular disk that surrounds it. The observations showed that the disk of dense material is orbiting within the galaxy's nucleus at velocities -- up to 650 miles per second -- that require the gravitational pull of such a massive object. The high angular resolution and sensitivity of the Very Long Baseline Array of the National Radio Astronomy Observatory allowed precise measurements of the differential rotation of the material in the disk, which provides the most direct and definitive evidence to date for the presence of a supermassive black hole in the center of another galaxy. Black holes, so dense that nothing -- not even light -- can escape their gravitational fields, have long been thought to be present in the centers of active galaxies, where they would act as central engines driving a variety of exotic and energetic phenomena that are seen on much larger scales, such as jets and powerful X ray emission. NGC 4258, a spiral some 90,000 light-years across, is known to have jets of gas that are twisted into the shape of a helix emerging from the nucleus at speeds of 400 miles per second. Makoto Miyoshi of Japan's Mizusawa Astrogeodymanics Observatory; James Moran, James Herrnstein and Lincoln Greenhill of the Harvard-Smithsonian Center for Astrophysics in Cambridge, MA; Naomasa Nakai of Japan's Nobeyama Radio Observatory; Philip Diamond of the

  8. Megacity precipitationsheds reveal tele-connected water security challenges

    Science.gov (United States)

    Wang-Erlandsson, Lan; Gordon, Line J.

    2018-01-01

    Urbanization is a global process that has taken billions of people from the rural countryside to concentrated urban centers, adding pressure to existing water resources. Many cities are specifically reliant on renewable freshwater regularly refilled by precipitation, rather than fossil groundwater or desalination. A precipitationshed can be considered the “watershed of the sky” and identifies the origin of precipitation falling in a given region. In this paper, we use this concept to determine the sources of precipitation that supply renewable water in the watersheds of the largest cities of the world. We quantify the sources of precipitation for 29 megacities and analyze their differences between dry and wet years. Our results reveal that 19 of 29 megacities depend for more than a third of their water supply on evaporation from land. We also show that for many of the megacities, the terrestrial dependence is higher in dry years. This high dependence on terrestrial evaporation for their precipitation exposes these cities to potential land-use change that could reduce the evaporation that generates precipitation. Combining indicators of water stress, moisture recycling exposure, economic capacity, vegetation-regulated evaporation, land-use change, and dry-season moisture recycling sensitivity reveals four highly vulnerable megacities (Karachi, Shanghai, Wuhan, and Chongqing). A further six megacities were found to have medium vulnerability with regard to their water supply. We conclude that understanding how upwind landscapes affect downwind municipal water resources could be a key component for understanding the complexity of urban water security. PMID:29534109

  9. The new galaxy evolution paradigm revealed by the Herschel surveys

    Science.gov (United States)

    Eales, Stephen; Smith, Dan; Bourne, Nathan; Loveday, Jon; Rowlands, Kate; van der Werf, Paul; Driver, Simon; Dunne, Loretta; Dye, Simon; Furlanetto, Cristina; Ivison, R. J.; Maddox, Steve; Robotham, Aaron; Smith, Matthew W. L.; Taylor, Edward N.; Valiante, Elisabetta; Wright, Angus; Cigan, Philip; De Zotti, Gianfranco; Jarvis, Matt J.; Marchetti, Lucia; Michałowski, Michał J.; Phillipps, Steven; Viaene, Sebastien; Vlahakis, Catherine

    2018-01-01

    The Herschel Space Observatory has revealed a very different galaxyscape from that shown by optical surveys which presents a challenge for galaxy-evolution models. The Herschel surveys reveal (1) that there was rapid galaxy evolution in the very recent past and (2) that galaxies lie on a single Galaxy Sequence (GS) rather than a star-forming 'main sequence' and a separate region of 'passive' or 'red-and-dead' galaxies. The form of the GS is now clearer because far-infrared surveys such as the Herschel ATLAS pick up a population of optically red star-forming galaxies that would have been classified as passive using most optical criteria. The space-density of this population is at least as high as the traditional star-forming population. By stacking spectra of H-ATLAS galaxies over the redshift range 0.001 high stellar masses, high star-formation rates but, even several billion years in the past, old stellar populations - they are thus likely to be relatively recent ancestors of early-type galaxies in the Universe today. The form of the GS is inconsistent with rapid quenching models and neither the analytic bathtub model nor the hydrodynamical EAGLE simulation can reproduce the rapid cosmic evolution. We propose a new gentler model of galaxy evolution that can explain the new Herschel results and other key properties of the galaxy population.

  10. The microbiome of Brazilian mangrove sediments as revealed by metagenomics.

    Directory of Open Access Journals (Sweden)

    Fernando Dini Andreote

    Full Text Available Here we embark in a deep metagenomic survey that revealed the taxonomic and potential metabolic pathways aspects of mangrove sediment microbiology. The extraction of DNA from sediment samples and the direct application of pyrosequencing resulted in approximately 215 Mb of data from four distinct mangrove areas (BrMgv01 to 04 in Brazil. The taxonomic approaches applied revealed the dominance of Deltaproteobacteria and Gammaproteobacteria in the samples. Paired statistical analysis showed higher proportions of specific taxonomic groups in each dataset. The metabolic reconstruction indicated the possible occurrence of processes modulated by the prevailing conditions found in mangrove sediments. In terms of carbon cycling, the sequences indicated the prevalence of genes involved in the metabolism of methane, formaldehyde, and carbon dioxide. With respect to the nitrogen cycle, evidence for sequences associated with dissimilatory reduction of nitrate, nitrogen immobilization, and denitrification was detected. Sequences related to the production of adenylsulfate, sulfite, and H(2S were relevant to the sulphur cycle. These data indicate that the microbial core involved in methane, nitrogen, and sulphur metabolism consists mainly of Burkholderiaceae, Planctomycetaceae, Rhodobacteraceae, and Desulfobacteraceae. Comparison of our data to datasets from soil and sea samples resulted in the allotment of the mangrove sediments between those samples. The results of this study add valuable data about the composition of microbial communities in mangroves and also shed light on possible transformations promoted by microbial organisms in mangrove sediments.

  11. The microbiome of Brazilian mangrove sediments as revealed by metagenomics.

    Science.gov (United States)

    Andreote, Fernando Dini; Jiménez, Diego Javier; Chaves, Diego; Dias, Armando Cavalcante Franco; Luvizotto, Danice Mazzer; Dini-Andreote, Francisco; Fasanella, Cristiane Cipola; Lopez, Maryeimy Varon; Baena, Sandra; Taketani, Rodrigo Gouvêa; de Melo, Itamar Soares

    2012-01-01

    Here we embark in a deep metagenomic survey that revealed the taxonomic and potential metabolic pathways aspects of mangrove sediment microbiology. The extraction of DNA from sediment samples and the direct application of pyrosequencing resulted in approximately 215 Mb of data from four distinct mangrove areas (BrMgv01 to 04) in Brazil. The taxonomic approaches applied revealed the dominance of Deltaproteobacteria and Gammaproteobacteria in the samples. Paired statistical analysis showed higher proportions of specific taxonomic groups in each dataset. The metabolic reconstruction indicated the possible occurrence of processes modulated by the prevailing conditions found in mangrove sediments. In terms of carbon cycling, the sequences indicated the prevalence of genes involved in the metabolism of methane, formaldehyde, and carbon dioxide. With respect to the nitrogen cycle, evidence for sequences associated with dissimilatory reduction of nitrate, nitrogen immobilization, and denitrification was detected. Sequences related to the production of adenylsulfate, sulfite, and H(2)S were relevant to the sulphur cycle. These data indicate that the microbial core involved in methane, nitrogen, and sulphur metabolism consists mainly of Burkholderiaceae, Planctomycetaceae, Rhodobacteraceae, and Desulfobacteraceae. Comparison of our data to datasets from soil and sea samples resulted in the allotment of the mangrove sediments between those samples. The results of this study add valuable data about the composition of microbial communities in mangroves and also shed light on possible transformations promoted by microbial organisms in mangrove sediments.

  12. [Research reveals a market for a veterinary behaviour clinic].

    Science.gov (United States)

    Jonckheer-Sheehy, Valerie; Endenburg, Nienke

    2009-11-01

    An enquiry into the requirement of a university veterinary behaviour clinic in The Netherlands revealed that there is a clear call for such a service. The specific demands and wishes of first line practicing veterinarians and companion animal owners were investigated. The research revealed that veterinarians are regular confronted with behaviour problems in companion animals and that they are willing to refer these cases to the University. They also expressed their need for access to continuing professional development opportunities in the field of veterinary behavioural medicine (which is something that most veterinary behaviour clinics associated with veterinary faculties provide). The demand from companion animal owners was also examined. It can be concluded that a large number of them had animals with behaviour problems and that they were willing to seek veterinary advice on these matters. In response to the above mentioned demands the University of Utrecht will open a veterinary behaviour clinic, providing high quality service for animals, their owners and the referring veterinarians. This service will be based on sound scientific practice and delivered by both veterinarians specialised in this field and recognised animal behaviour therapists.

  13. King Lear Reveals the Tragic Pattern of Shakespeare

    Directory of Open Access Journals (Sweden)

    Salim Eflih Al-Ibia

    2017-04-01

    Full Text Available Rather than focusing on the obvious traditions of evaluating Shakespearean tragic heroes, this paper presents a groundbreaking approach to unfold the pattern William Shakespeare follows as he designed his unique characters. This pattern applies to most, if not all, Shakespearean tragic heroes. I argue that Shakespeare himself reveals a great portion of this pattern on the tongue of Lear as the latter disowns Goneril and Regan promising to have “such revenges on [them] both” in King Lear. Lear’s threats bestow four unique aspects that apply not only to his character but they also apply to Shakespearean tragic heroes. Lear’s speech tells us that he is determined to have an awful type of revenge on his daughters. However, the very same speech tells us that he seems uncertain about the method through which he should carry out this revenge. Lear does not express any type of remorse as he pursues his vengeful plans nor should he aim at amnesty. He also admits his own madness as he closes his revealing speech. This research develops these facts about Lear to unfold the unique pattern Shakespeare follows as he portrayed his major tragic figures. This pattern is examined, described and analyzed in King Lear, Othello, and Hamlet. We will find out that the pattern suggested in this study helps us better understand Shakespeare’s tragedies and enables us to provide better explanations for some controversial scenes in the tragedies discussed.

  14. Unilateral proptosis revealing a fronto-ethmoidal mucocele.

    Science.gov (United States)

    Lajmi, Houda; Hmaied, Wassim; Ben Jalel, Wady; Ben Romdhane, Khaoula; Chelly, Zied; El Fekih, Lamia

    2017-06-01

    Backgroud: The fronto-ethmoidal mucocele is a benign condition leading commonly to limited eye movement or ocular pain but it could also induce visual acuity impairment by compressing the optic nerve Aim: To discuss, through a case report, different ophthalmologic manifestations of the fronto-ethmoidalmucocele. Reported case: A 46-years-old man with no general history consulted for a bilateral ocular redness and itching. He reported, however, a mild protrusion of his left globe evolving for oneyear. The clinical examination revealed a unilateral proptosis in the left eye with a discrete limitation of theadduction. A brain and orbital computer tomography (CT)and a magnetic resonance imaging(MRI)revealed a grade I exophthalmos caused by an oval formation of fluid density in the left anterior and posterior ethmoidal cells in addition to the frontal sinus,driving theeyeball and internal oculomotor muscles back and out.The patient was referred to otorhinolaryngology department for a precocious surgical management. The ophtalmologic manifestations of the disease depend on the location, the size of the formation and involvement of adjacent structures. The loss of vision and the apex syndrome due to the compressionof the ocular globe are the most serious complications.

  15. Membrane Protein Properties Revealed through Data-Rich Electrostatics Calculations.

    Science.gov (United States)

    Marcoline, Frank V; Bethel, Neville; Guerriero, Christopher J; Brodsky, Jeffrey L; Grabe, Michael

    2015-08-04

    The electrostatic properties of membrane proteins often reveal many of their key biophysical characteristics, such as ion channel selectivity and the stability of charged membrane-spanning segments. The Poisson-Boltzmann (PB) equation is the gold standard for calculating protein electrostatics, and the software APBSmem enables the solution of the PB equation in the presence of a membrane. Here, we describe significant advances to APBSmem, including full automation of system setup, per-residue energy decomposition, incorporation of PDB2PQR, calculation of membrane-induced pKa shifts, calculation of non-polar energies, and command-line scripting for large-scale calculations. We highlight these new features with calculations carried out on a number of membrane proteins, including the recently solved structure of the ion channel TRPV1 and a large survey of 1,614 membrane proteins of known structure. This survey provides a comprehensive list of residues with large electrostatic penalties for being embedded in the membrane, potentially revealing interesting functional information. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Economic choices reveal probability distortion in macaque monkeys.

    Science.gov (United States)

    Stauffer, William R; Lak, Armin; Bossaerts, Peter; Schultz, Wolfram

    2015-02-18

    Economic choices are largely determined by two principal elements, reward value (utility) and probability. Although nonlinear utility functions have been acknowledged for centuries, nonlinear probability weighting (probability distortion) was only recently recognized as a ubiquitous aspect of real-world choice behavior. Even when outcome probabilities are known and acknowledged, human decision makers often overweight low probability outcomes and underweight high probability outcomes. Whereas recent studies measured utility functions and their corresponding neural correlates in monkeys, it is not known whether monkeys distort probability in a manner similar to humans. Therefore, we investigated economic choices in macaque monkeys for evidence of probability distortion. We trained two monkeys to predict reward from probabilistic gambles with constant outcome values (0.5 ml or nothing). The probability of winning was conveyed using explicit visual cues (sector stimuli). Choices between the gambles revealed that the monkeys used the explicit probability information to make meaningful decisions. Using these cues, we measured probability distortion from choices between the gambles and safe rewards. Parametric modeling of the choices revealed classic probability weighting functions with inverted-S shape. Therefore, the animals overweighted low probability rewards and underweighted high probability rewards. Empirical investigation of the behavior verified that the choices were best explained by a combination of nonlinear value and nonlinear probability distortion. Together, these results suggest that probability distortion may reflect evolutionarily preserved neuronal processing. Copyright © 2015 Stauffer et al.

  17. Ananke: temporal clustering reveals ecological dynamics of microbial communities

    Directory of Open Access Journals (Sweden)

    Michael W. Hall

    2017-09-01

    Full Text Available Taxonomic markers such as the 16S ribosomal RNA gene are widely used in microbial community analysis. A common first step in marker-gene analysis is grouping genes into clusters to reduce data sets to a more manageable size and potentially mitigate the effects of sequencing error. Instead of clustering based on sequence identity, marker-gene data sets collected over time can be clustered based on temporal correlation to reveal ecologically meaningful associations. We present Ananke, a free and open-source algorithm and software package that complements existing sequence-identity-based clustering approaches by clustering marker-gene data based on time-series profiles and provides interactive visualization of clusters, including highlighting of internal OTU inconsistencies. Ananke is able to cluster distinct temporal patterns from simulations of multiple ecological patterns, such as periodic seasonal dynamics and organism appearances/disappearances. We apply our algorithm to two longitudinal marker gene data sets: faecal communities from the human gut of an individual sampled over one year, and communities from a freshwater lake sampled over eleven years. Within the gut, the segregation of the bacterial community around a food-poisoning event was immediately clear. In the freshwater lake, we found that high sequence identity between marker genes does not guarantee similar temporal dynamics, and Ananke time-series clusters revealed patterns obscured by clustering based on sequence identity or taxonomy. Ananke is free and open-source software available at https://github.com/beiko-lab/ananke.

  18. [Mutism and acute behavioral disorders revealing MELAS syndrome].

    Science.gov (United States)

    Coomans, H; Barroso, B; Bertandeau, E; Bonnan, M; Dakar, A; Demasles, S; Garraud, S; Krim, E; Martin-Négrier, M-L

    2011-11-01

    MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) is a rare genetic mitochondrial disease which can cause cerebral (cerebrovascular accident, migraine, mental deterioration..), sensorial (bilateral symmetrical deafness) and peripheral (muscular involvement, neuropathy) disorders potentially associated with diabetes, renal or cardiac disorders, or growth retardation. Eighty percent of the patients have the 3243 A>G mutation in the leucine RNA transfer gene. Clinical manifestations leading to discovery of the mutation can be extremely varied, affecting patients of different age groups. We report the case of a 49-year-old man who presented acute fits of confusion followed by mutism and praxic disorders. History taking revealed recently diagnosed type 2 diabetes, axonal neuropathy, and bilateral symmetrical deafness requiring hearing aids. The initial MRI showed FLAIR sequences with bi-parietal abnormalities, no signs of recent stroke on the DW/B10000 sequences, and basal ganglia calcifications. Blood tests and morphological findings ruled out a vascular origin. Search for lactic acidosis remained constantly negative in blood samples despite positive cerebrospinal fluid samples (N×3). The 3243 A>G mitochondrial DNA mutation was identified. The neuropsychological evaluation revealed a serious dysexecutive syndrome with a major impact on the patient's self sufficiency. Neurocognitive disorders are not common in MELAS syndrome. Brain MRI results and the presence of extra-neurological signs can be helpful for diagnosis. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  19. Differential metabolism of Mycoplasma species as revealed by their genomes

    Directory of Open Access Journals (Sweden)

    Fabricio B.M. Arraes

    2007-01-01

    Full Text Available The annotation and comparative analyses of the genomes of Mycoplasma synoviae and Mycoplasma hyopneumonie, as well as of other Mollicutes (a group of bacteria devoid of a rigid cell wall, has set the grounds for a global understanding of their metabolism and infection mechanisms. According to the annotation data, M. synoviae and M. hyopneumoniae are able to perform glycolytic metabolism, but do not possess the enzymatic machinery for citrate and glyoxylate cycles, gluconeogenesis and the pentose phosphate pathway. Both can synthesize ATP by lactic fermentation, but only M. synoviae can convert acetaldehyde to acetate. Also, our genome analysis revealed that M. synoviae and M. hyopneumoniae are not expected to synthesize polysaccharides, but they can take up a variety of carbohydrates via the phosphoenolpyruvate-dependent phosphotransferase system (PEP-PTS. Our data showed that these two organisms are unable to synthesize purine and pyrimidine de novo, since they only possess the sequences which encode salvage pathway enzymes. Comparative analyses of M. synoviae and M. hyopneumoniae with other Mollicutes have revealed differential genes in the former two genomes coding for enzymes that participate in carbohydrate, amino acid and nucleotide metabolism and host-pathogen interaction. The identification of these metabolic pathways will provide a better understanding of the biology and pathogenicity of these organisms.

  20. NeuCode Proteomics Reveals Bap1 Regulation of Metabolism

    Directory of Open Access Journals (Sweden)

    Joshua M. Baughman

    2016-07-01

    Full Text Available We introduce neutron-encoded (NeuCode amino acid labeling of mice as a strategy for multiplexed proteomic analysis in vivo. Using NeuCode, we characterize an inducible knockout mouse model of Bap1, a tumor suppressor and deubiquitinase whose in vivo roles outside of cancer are not well established. NeuCode proteomics revealed altered metabolic pathways following Bap1 deletion, including profound elevation of cholesterol biosynthetic machinery coincident with reduced expression of gluconeogenic and lipid homeostasis proteins in liver. Bap1 loss increased pancreatitis biomarkers and reduced expression of mitochondrial proteins. These alterations accompany a metabolic remodeling with hypoglycemia, hypercholesterolemia, hepatic lipid loss, and acinar cell degeneration. Liver-specific Bap1 null mice present with fully penetrant perinatal lethality, severe hypoglycemia, and hepatic lipid deficiency. This work reveals Bap1 as a metabolic regulator in liver and pancreas, and it establishes NeuCode as a reliable proteomic method for deciphering in vivo biology.

  1. Disrupted topological organization of structural networks revealed by probabilistic diffusion tractography in Tourette syndrome children.

    Science.gov (United States)

    Wen, Hongwei; Liu, Yue; Rekik, Islem; Wang, Shengpei; Zhang, Jishui; Zhang, Yue; Peng, Yun; He, Huiguang

    2017-08-01

    Tourette syndrome (TS) is a childhood-onset neurobehavioral disorder. Although previous TS studies revealed structural abnormalities in distinct corticobasal ganglia circuits, the topological alterations of the whole-brain white matter (WM) structural networks remain poorly understood. Here, we used diffusion MRI probabilistic tractography and graph theoretical analysis to investigate the topological organization of WM networks in 44 drug-naive TS children and 41 age- and gender-matched healthy children. The WM networks were constructed by estimating inter-regional connectivity probability and the topological properties were characterized using graph theory. We found that both TS and control groups showed an efficient small-world organization in WM networks. However, compared to controls, TS children exhibited decreased global and local efficiency, increased shortest path length and small worldness, indicating a disrupted balance between local specialization and global integration in structural networks. Although both TS and control groups showed highly similar hub distributions, TS children exhibited significant decreased nodal efficiency, mainly distributed in the default mode, language, visual, and sensorimotor systems. Furthermore, two separate networks showing significantly decreased connectivity in TS group were identified using network-based statistical (NBS) analysis, primarily composed of the parieto-occipital cortex, precuneus, and paracentral lobule. Importantly, we combined support vector machine and multiple kernel learning frameworks to fuse multiple levels of network topological features for classification of individuals, achieving high accuracy of 86.47%. Together, our study revealed the disrupted topological organization of structural networks related to pathophysiology of TS, and the discriminative topological features for classification are potential quantitative neuroimaging biomarkers for clinical TS diagnosis. Hum Brain Mapp 38:3988-4008, 2017

  2. Arterial spin labelling reveals prolonged arterial arrival time in idiopathic Parkinson's disease.

    Science.gov (United States)

    Al-Bachari, Sarah; Parkes, Laura M; Vidyasagar, Rishma; Hanby, Martha F; Tharaken, Vivek; Leroi, Iracema; Emsley, Hedley C A

    2014-01-01

    Idiopathic Parkinson's disease (IPD) is the second most common neurodegenerative disease, yet effective disease modifying treatments are still lacking. Neurodegeneration involves multiple interacting pathological pathways. The extent to which neurovascular mechanisms are involved is not well defined in IPD. We aimed to determine whether novel magnetic resonance imaging (MRI) techniques, including arterial spin labelling (ASL) quantification of cerebral perfusion, can reveal altered neurovascular status (NVS) in IPD. Fourteen participants with IPD (mean ± SD age 65.1 ± 5.9 years) and 14 age and cardiovascular risk factor matched control participants (mean ± SD age 64.6 ± 4.2 years) underwent a 3T MRI scan protocol. ASL images were collected before, during and after a 6 minute hypercapnic challenge. FLAIR images were used to determine white matter lesion score. Quantitative images of cerebral blood flow (CBF) and arterial arrival time (AAT) were calculated from the ASL data both at rest and during hypercapnia. Cerebrovascular reactivity (CVR) images were calculated, depicting the change in CBF and AAT relative to the change in end-tidal CO2. A significant (p = 0.005) increase in whole brain averaged baseline AAT was observed in IPD participants (mean ± SD age 1532 ± 138 ms) compared to controls (mean ± SD age 1335 ± 165 ms). Voxel-wise analysis revealed this to be widespread across the brain. However, there were no statistically significant differences in white matter lesion score, CBF, or CVR between patients and controls. Regional CBF, but not AAT, in the IPD group was found to correlate positively with Montreal cognitive assessment (MoCA) scores. These findings provide further evidence of alterations in NVS in IPD.

  3. Flow Control

    Science.gov (United States)

    2013-04-08

    can be written as â fj (t) =WO tanh( WIx (t)+bI)+bO, (38) where WI , WO are the input and output matrices, respectively, and bI and bO are the input...applications, present on envisioned airborne optical platforms . One of the problems is that all adaptive optical systems rely on mechanically moving some...of successfully controlling the optical aberration due to the flow over the aperture of airborne optical platforms . As outlined above, systems

  4. A Survey of Electronic Serials Managers Reveals Diversity in Practice

    Directory of Open Access Journals (Sweden)

    Laura Costello

    2014-09-01

    Full Text Available A Review of: Branscome, B. A. (2013. Management of electronic serials in academic libraries: The results of an online survey. Serials Review, 39(4, 216-226. http://dx.doi.org/10.1016/j.serrev.2013.10.004 Abstract Objective – To examine industry standards for the management of electronic serials and measure the adoption of electronic serials over print. Design – Survey questionnaire. Setting – Email lists aimed at academic librarians working in serials management. Subjects – 195 self-selected subscribers to serials email lists. Methods – The author created a 20 question survey that consisted primarily of closed-ended questions pertaining to the collection demographics, staff, budget, and tools of serials management groups in academic libraries. The survey was conducted via Survey Monkey and examined using the analytical features of the tool. Participants remained anonymous and the survey questions did not ask them to reveal identifiable information about their libraries. Main Results – Collection demographics questions revealed that 78% of surveyed librarians estimated that print-only collections represented 40% or fewer of their serials holdings. The author observed diversity in the factors that influence print to digital transitions in academic libraries. However 71.5% of participants indicated that publisher technology support like IP authentication was required before adopting digital subscriptions. A lack of standardization also marked serials workflows, department responsibilities, and department titles. The author did not find a correlation between serials budget and the enrollment size of the institution. Participants reported that they used tools from popular serials management vendors like Serials Solutions, Innovative Interfaces, EBSCO, and Ex Libris, but most indicated that they used more than one tool for serials management. Participants specified 52 unique serials management products used in their libraries. Conclusion

  5. Revisiting the Strange Stories: Revealing Mentalizing Impairments in Autism

    Science.gov (United States)

    White, Sarah; Hill, Elisabeth; Happe, Francesca; Frith, Uta

    2009-01-01

    A test of advanced theory of mind (ToM), first introduced by F. Happe (1994), was adapted for children (mental, human, animal, and nature stories plus unlinked sentences). These materials were closely matched for difficulty and were presented to forty-five 7- to 12-year-olds with autism and 27 control children. Children with autism who showed ToM…

  6. Dislocation Interactions in Olivine Revealed by HR-EBSD

    NARCIS (Netherlands)

    Wallis, D.; Hansen, Lars N.; Britton, T. Ben; Wilkinson, Angus J.

    2017-01-01

    Interactions between dislocations potentially provide a control on strain rates produced bydislocation motion during creep of rocks at high temperatures. However, it has been difficult to establishthe dominant types of interactions and their influence on the rheological properties of creeping rocks

  7. Serial functional imaging poststroke reveals visual cortex reorganization.

    Science.gov (United States)

    Brodtmann, Amy; Puce, Aina; Darby, David; Donnan, Geoffrey

    2009-02-01

    Visual cortical reorganization following injury remains poorly understood. The authors performed serial functional magnetic resonance imaging (fMRI) on patients with visual cortex infarction to evaluate early and late striate, ventral, and dorsal extrastriate cortical activation. Patients were studied with fMRI within 10 days and at 6 months. The authors used a high-level visual activation task designed to activate the ventral extrastriate cortex. These data were compared to those of age-appropriate healthy control participants. The results from 24 healthy control individuals (mean age 65.7 +/- SE 3.6 years, range 32-89) were compared to those from 5 stroke patients (mean age 73.8 +/- SE 7 years, range 49-86). Patients had infarcts involving the striate and ventral extrastriate cortex. Patient activation patterns were markedly different to controls. Bilateral striate and ventral extrastriate activation was reduced at both sessions, but dorsal extrastriate activated voxel counts remained comparable to controls. Conversely, mean percent magnetic resonance signal change increased in dorsal sites. These data provide strong evidence of bilateral poststroke functional depression of striate and ventral extrastriate cortices. Possible utilization or surrogacy of the dorsal visual system was demonstrated following stroke. This activity could provide a target for novel visual rehabilitation therapies.

  8. Measles outbreak reveals measles susceptibility among adults in ...

    African Journals Online (AJOL)

    Background. The World Health Organization, African Region, set the goal of achieving measles elimination by 2020. Namibia was one of seven African countries to implement an accelerated measles control strategy beginning in 1996. Following implementation of this strategy, measles incidence decreased; however, ...

  9. Mitochondrial DNA analysis reveals a low nucleotide diversity of ...

    African Journals Online (AJOL)

    Caligula japonica (Lepidoptera: Saturniidae), an endemic species in Eastern Asia, is not only an economically important pest to be controlled, but also a producer of expensive silk. We have demonstrated previously the presence of a higher genetic diversity and a certain degree of genetic differentiation related to ...

  10. Diffusion Tensor Tractography Reveals Disrupted Structural Connectivity during Brain Aging

    Science.gov (United States)

    Lin, Lan; Tian, Miao; Wang, Qi; Wu, Shuicai

    2017-10-01

    Brain aging is one of the most crucial biological processes that entail many physical, biological, chemical, and psychological changes, and also a major risk factor for most common neurodegenerative diseases. To improve the quality of life for the elderly, it is important to understand how the brain is changed during the normal aging process. We compared diffusion tensor imaging (DTI)-based brain networks in a cohort of 75 healthy old subjects by using graph theory metrics to describe the anatomical networks and connectivity patterns, and network-based statistic (NBS) analysis was used to identify pairs of regions with altered structural connectivity. The NBS analysis revealed a significant network comprising nine distinct fiber bundles linking 10 different brain regions showed altered white matter structures in young-old group compare with middle-aged group (p < .05, family-wise error-corrected). Our results might guide future studies and help to gain a better understanding of brain aging.

  11. Principles of Chromosome Architecture Revealed by Hi-C.

    Science.gov (United States)

    Eagen, Kyle P

    2018-06-01

    Chromosomes are folded and compacted in interphase nuclei, but the molecular basis of this folding is poorly understood. Chromosome conformation capture methods, such as Hi-C, combine chemical crosslinking of chromatin with fragmentation, DNA ligation, and high-throughput DNA sequencing to detect neighboring loci genome-wide. Hi-C has revealed the segregation of chromatin into active and inactive compartments and the folding of DNA into self-associating domains and loops. Depletion of CTCF, cohesin, or cohesin-associated proteins was recently shown to affect the majority of domains and loops in a manner that is consistent with a model of DNA folding through extrusion of chromatin loops. Compartmentation was not dependent on CTCF or cohesin. Hi-C contact maps represent the superimposition of CTCF/cohesin-dependent and -independent folding states. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. The hand of birds revealed by early ostrich embryos

    Science.gov (United States)

    Feduccia, Alan; Nowicki, Julie

    2002-08-01

    The problem of resolving the homology of the digits of the avian hand has been framed as a conflict between paleontological and embryological evidence, the former thought to support a hand composed of digits I, II, III, because of similarity of the phalangeal formulae of the earliest known bird Archaeopteryx to that of Mesozoic pentadactyl archosaurs, while embryological evidence has traditionally favored a II, III, IV avian hand. We have identified the critical developmental period for the major features of the avian skeleton in a primitive bird, the ostrich. Analysis of digit anlagen in the avian hand has revealed those for digits/metacarpals I and V, thus confirming previous embryological studies that indirectly suggested that the avian hand comprises digits II, III, IV, and was primitively pentadactyl.

  13. Dinosaurs reveal the geographical signature of an evolutionary radiation.

    Science.gov (United States)

    O'Donovan, Ciara; Meade, Andrew; Venditti, Chris

    2018-03-01

    Dinosaurs dominated terrestrial ecosystems across the globe for over 100 million years and provide a classic example of an evolutionary radiation. However, little is known about how these animals radiated geographically to become globally distributed. Here, we use a biogeographical model to reconstruct the dinosaurs' ancestral locations, revealing the spatial mechanisms that underpinned this 170-million-year-long radiation. We find that dinosaurs spread rapidly initially, followed by a significant continuous and gradual reduction in their speed of movement towards the Cretaceous/Tertiary boundary (66 million years ago). This suggests that the predominant mode of dinosaur speciation changed through time with speciation originally largely driven by geographical isolation-when dinosaurs speciated more, they moved further. This was gradually replaced by increasing levels of sympatric speciation (species taking advantage of ecological opportunities within their existing environment) as terrestrial space became a limiting factor. Our results uncover the geographical signature of an evolutionary radiation.

  14. Bibliometric Analyses Reveal Patterns of Collaboration between ASMS Members

    Science.gov (United States)

    Palmblad, Magnus; van Eck, Nees Jan

    2018-03-01

    We have explored the collaborative network of the current American Society for Mass Spectrometry (ASMS) membership using bibliometric methods. The analysis shows that 4249 members are connected in a single, large, co-authorship graph, including the majority of the most published authors in the field of mass spectrometry. The map reveals topographical differences between university groups and national laboratories, and that the co-authors with the strongest links have long worked together at the same location. We have collected and summarized information on the geographical distribution of members, showing a high coverage of active researchers in North America and Western Europe. Looking at research fields, we could also identify a number of new or `hot' topics among ASMS members. Interactive versions of the maps are available on-line at https://goo.gl/UBNFMQ (collaborative network) and https://goo.gl/WV25vm (research topics). [Figure not available: see fulltext.

  15. [Clinical case of acute renal failure revealing an autoimmune hypothyroidism].

    Science.gov (United States)

    Montasser, Dina Ibrahim; Hassani, Mohamed; Zajjari, Yassir; Bahadi, Abdelali; Alayoud, Ahmed; Hamzi, Amine; Hassani, Kawtar; Moujoud, Omar; Asseraji, Mohamed; Kadiri, Moncif; Aatif, Taoufik; El Kabbaj, Driss; Benyahia, Mohamed; Allam, Mustapha; Akhmouch, Ismail; Oualim, Zouhir

    2010-04-01

    Although the clinic picture is often indicative of muscle manifestations in patients with hypothyroidism, signs and symptoms of this condition are variable from simple elevation of serum muscle enzymes with myalgia, muscle weakness, cramps to rhabdomyolysis with acute renal failure which remains a rare event. Thyroid hormones affect the function of almost every body organ, and thyroid dysfunction produces a wide range of metabolic disturbances. Hypothyroidism is associated with significant effects on the kidney which the pathophysiology seems to be multifactorial, but the exact mechanisms remain poorly understood. Hypothyroidism as a cause of renal impairment is usually overlooked, leading to unnecessary diagnostic procedures. The main objective of our observation is to report a case of acute renal failure revealing an autoimmune hypothyroidism in which thyroid hormone substitution led to a significant improvement in muscular, thyroid and renal disorders. Copyright 2010 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  16. Deciphering CAPTCHAs: what a Turing test reveals about human cognition.

    Directory of Open Access Journals (Sweden)

    Thomas Hannagan

    Full Text Available Turning Turing's logic on its head, we used widespread letter-based Turing Tests found on the internet (CAPTCHAs to shed light on human cognition. We examined the basis of the human ability to solve CAPTCHAs, where machines fail. We asked whether this is due to our use of slow-acting inferential processes that would not be available to machines, or whether fast-acting automatic orthographic processing in humans has superior robustness to shape variations. A masked priming lexical decision experiment revealed efficient processing of CAPTCHA words in conditions that rule out the use of slow inferential processing. This shows that the human superiority in solving CAPTCHAs builds on a high degree of invariance to location and continuous transforms, which is achieved during the very early stages of visual word recognition in skilled readers.

  17. Adipsic diabetes insipidus revealing a bifocal intracranial germinoma.

    Science.gov (United States)

    Kreutz, Julie; Potorac, Iulia; Lutteri, Laurence; Gennigens, Christine; Martin, Didier; Daly, Adrian F; Bonneville, Jean-Francois; Tshibanda, Luaba; Beckers, Albert

    2017-07-01

    Adipsic diabetes insipidus is a rare complication of intracranial tumors in which impaired antidiuretic hormone secretion is associated with the loss of thirst sensation. Here, we present the case of a patient with bifocal intracranial germinoma, diagnosed due to symptoms mainly caused by adipsic diabetes insipidus. This is, to our knowledge, the first case of adipsic diabetes insipidus revealing an intracranial germinoma reported in the literature. We describe the diagnostic procedures and the three-year follow-up of this patient. Management of intracranial germ-cell tumors is made complex by the wide range of histological features. Although germinomas have a generally better prognosis than most nongerminomatous tumors, they can have severe or even life-threatening presentations. Adipsic diabetes insipidus is one such severe presentation and its rarity can make it difficult to recognize and manage. Awareness of this potential entity is therefore important for clinical practice. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Comparative genomics reveals insights into avian genome evolution and adaptation

    Science.gov (United States)

    Zhang, Guojie; Li, Cai; Li, Qiye; Li, Bo; Larkin, Denis M.; Lee, Chul; Storz, Jay F.; Antunes, Agostinho; Greenwold, Matthew J.; Meredith, Robert W.; Ödeen, Anders; Cui, Jie; Zhou, Qi; Xu, Luohao; Pan, Hailin; Wang, Zongji; Jin, Lijun; Zhang, Pei; Hu, Haofu; Yang, Wei; Hu, Jiang; Xiao, Jin; Yang, Zhikai; Liu, Yang; Xie, Qiaolin; Yu, Hao; Lian, Jinmin; Wen, Ping; Zhang, Fang; Li, Hui; Zeng, Yongli; Xiong, Zijun; Liu, Shiping; Zhou, Long; Huang, Zhiyong; An, Na; Wang, Jie; Zheng, Qiumei; Xiong, Yingqi; Wang, Guangbiao; Wang, Bo; Wang, Jingjing; Fan, Yu; da Fonseca, Rute R.; Alfaro-Núñez, Alonzo; Schubert, Mikkel; Orlando, Ludovic; Mourier, Tobias; Howard, Jason T.; Ganapathy, Ganeshkumar; Pfenning, Andreas; Whitney, Osceola; Rivas, Miriam V.; Hara, Erina; Smith, Julia; Farré, Marta; Narayan, Jitendra; Slavov, Gancho; Romanov, Michael N; Borges, Rui; Machado, João Paulo; Khan, Imran; Springer, Mark S.; Gatesy, John; Hoffmann, Federico G.; Opazo, Juan C.; Håstad, Olle; Sawyer, Roger H.; Kim, Heebal; Kim, Kyu-Won; Kim, Hyeon Jeong; Cho, Seoae; Li, Ning; Huang, Yinhua; Bruford, Michael W.; Zhan, Xiangjiang; Dixon, Andrew; Bertelsen, Mads F.; Derryberry, Elizabeth; Warren, Wesley; Wilson, Richard K; Li, Shengbin; Ray, David A.; Green, Richard E.; O’Brien, Stephen J.; Griffin, Darren; Johnson, Warren E.; Haussler, David; Ryder, Oliver A.; Willerslev, Eske; Graves, Gary R.; Alström, Per; Fjeldså, Jon; Mindell, David P.; Edwards, Scott V.; Braun, Edward L.; Rahbek, Carsten; Burt, David W.; Houde, Peter; Zhang, Yong; Yang, Huanming; Wang, Jian; Jarvis, Erich D.; Gilbert, M. Thomas P.; Wang, Jun

    2015-01-01

    Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses reveal that pan-avian genomic diversity covaries with adaptations to different lifestyles and convergent evolution of traits. PMID:25504712

  19. Heat islands over Mumbai as revealed by autorecorded thermograph data

    Science.gov (United States)

    Srivastava, A. K.; Voogt, James; Kshirsagar, S. R.; Srivastava, Kavita

    2016-02-01

    This study examined hourly temperature data of two locations of Mumbai metropolitan city. One data point (Coloba, Mumbai) is in centre of the city and the other one (Santacruz, Mumbai) is at the airport. The study finds that there were many occasions when night-time hourly temperatures over the city centre were considerably higher than that of the airport, even though temperature at the time of sunset at both the places was nearly same. In this study, the occasions, when hourly night-time temperature over city was more than that of the airport by objectively defined threshold value (3.0 ∘C in this study) for most of the hours in the night, were termed as heat island events. Analysis of the study reveals that these events are mostly confined to November-February months. The study also found that frequency of such events has doubled in recent two decades in comparison to the earlier two decades.

  20. High-frequency microrheology reveals cytoskeleton dynamics in living cells

    Science.gov (United States)

    Rigato, Annafrancesca; Miyagi, Atsushi; Scheuring, Simon; Rico, Felix

    2017-08-01

    Living cells are viscoelastic materials, dominated by an elastic response on timescales longer than a millisecond. On shorter timescales, the dynamics of individual cytoskeleton filaments are expected to emerge, but active microrheology measurements on cells accessing this regime are scarce. Here, we develop high-frequency microrheology experiments to probe the viscoelastic response of living cells from 1 Hz to 100 kHz. We report the viscoelasticity of different cell types under cytoskeletal drug treatments. On previously inaccessible short timescales, cells exhibit rich viscoelastic responses that depend on the state of the cytoskeleton. Benign and malignant cancer cells revealed remarkably different scaling laws at high frequencies, providing a unique mechanical fingerprint. Microrheology over a wide dynamic range--up to the frequency characterizing the molecular components--provides a mechanistic understanding of cell mechanics.

  1. Biosensor reveals multiple sources for mitochondrial NAD⁺.

    Science.gov (United States)

    Cambronne, Xiaolu A; Stewart, Melissa L; Kim, DongHo; Jones-Brunette, Amber M; Morgan, Rory K; Farrens, David L; Cohen, Michael S; Goodman, Richard H

    2016-06-17

    Nicotinamide adenine dinucleotide (NAD(+)) is an essential substrate for sirtuins and poly(adenosine diphosphate-ribose) polymerases (PARPs), which are NAD(+)-consuming enzymes localized in the nucleus, cytosol, and mitochondria. Fluctuations in NAD(+) concentrations within these subcellular compartments are thought to regulate the activity of NAD(+)-consuming enzymes; however, the challenge in measuring compartmentalized NAD(+) in cells has precluded direct evidence for this type of regulation. We describe the development of a genetically encoded fluorescent biosensor for directly monitoring free NAD(+) concentrations in subcellular compartments. We found that the concentrations of free NAD(+) in the nucleus, cytoplasm, and mitochondria approximate the Michaelis constants for sirtuins and PARPs in their respective compartments. Systematic depletion of enzymes that catalyze the final step of NAD(+) biosynthesis revealed cell-specific mechanisms for maintaining mitochondrial NAD(+) concentrations. Copyright © 2016, American Association for the Advancement of Science.

  2. Between Concealing and Revealing Intersexed Bodies: Parental Strategies.

    Science.gov (United States)

    Danon, Limor Meoded; Krämer, Anike

    2017-08-01

    Parents of intersex children are perceived in many studies as hopeless, highly dependent on the medical system, and as gate keepers of normative gendered bodies. In this article, we challenge these perceptions and argue that parents of intersex children are problematically positioned between their children's needs for care and well-being and the socialmedical forces that aim to "normalize" them. Their in-between position leads them to establish different parental strategies within and outside of traditional sex/gender norms. We focus on three intertwined parental strategy frameworks: bodily dialogue, sex/gender framing, and concealing/revealing practices, and describe how, in each of these strategic frameworks, the parents maneuver, act in accordance with or against, react to, and challenge the medical system, social interactions, and the sex/gender paradigm. This is a comparative study based on narrative interviews with 22 parents of intersex children in Germany and Israel.

  3. Metabolomics reveals metabolic biomarkers of Crohn's disease

    Energy Technology Data Exchange (ETDEWEB)

    Jansson, J.K.; Willing, B.; Lucio, M.; Fekete, A.; Dicksved, J.; Halfvarson, J.; Tysk, C.; Schmitt-Kopplin, P.

    2009-06-01

    The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass Spectrometry (ICR-FT/MS) was used to discern the masses of thousands of metabolites in fecal samples collected from 17 identical twin pairs, including healthy individuals and those with CD. Pathways with differentiating metabolites included those involved in the metabolism and or synthesis of amino acids, fatty acids, bile acids and arachidonic acid. Several metabolites were positively or negatively correlated to the disease phenotype and to specific microbes previously characterized in the same samples. Our data reveal novel differentiating metabolites for CD that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention.

  4. Revealing low-energy part of the beta spectra

    International Nuclear Information System (INIS)

    Selvi, S.; Celiktas, C.

    2002-01-01

    An effective method is proposed to separate electronic noise from the beta-particle spectra revealing lower energy part of the spectra. The available methods for reducing the noise problem cut the noise along with the low-energy part of the beta spectra by using a discriminator. Our setup eliminates this undesirable effect by shifting the noise toward the lowest energy scale leaving the low-energy part of spectra undisturbed. We achieved this noise-pulse-separation by treating the noise as a pulse so that we can exploit the application of the pulse-shape analyzer equipment used for pulse shape identification of particles and rejection of defective pulses. To the best of our knowledge this method of the noise separation is a novel approach

  5. Tyrannosauroid integument reveals conflicting patterns of gigantism and feather evolution.

    Science.gov (United States)

    Bell, Phil R; Campione, Nicolás E; Persons, W Scott; Currie, Philip J; Larson, Peter L; Tanke, Darren H; Bakker, Robert T

    2017-06-01

    Recent evidence for feathers in theropods has led to speculations that the largest tyrannosaurids, including Tyrannosaurus rex , were extensively feathered. We describe fossil integument from Tyrannosaurus and other tyrannosaurids ( Albertosaurus, Daspletosaurus, Gorgosaurus and Tarbosaurus ), confirming that these large-bodied forms possessed scaly, reptilian-like skin. Body size evolution in tyrannosauroids reveals two independent occurrences of gigantism; specifically, the large sizes in Yutyrannus and tyrannosaurids were independently derived. These new findings demonstrate that extensive feather coverings observed in some early tyrannosauroids were lost by the Albian, basal to Tyrannosauridae. This loss is unrelated to palaeoclimate but possibly tied to the evolution of gigantism, although other mechanisms exist. © 2017 The Author(s).

  6. Upper Palaeolithic Siberian genome reveals dual ancestry of Native Americans

    DEFF Research Database (Denmark)

    Raghavan, Maanasa; Skoglund, Pontus; Graf, Kelly E.

    2014-01-01

    ,000-year-old individual (MA-1), from Mal'ta in south-central Siberia, to an average depth of 1×. To our knowledge this is the oldest anatomically modern human genome reported to date. The MA-1 mitochondrial genome belongs to haplogroup U, which has also been found at high frequency among Upper Palaeolithic......The origins of the First Americans remain contentious. Although Native Americans seem to be genetically most closely related to east Asians, there is no consensus with regard to which specific Old World populations they are closest to. Here we sequence the draft genome of an approximately 24...... that the region was continuously occupied by humans throughout the Last Glacial Maximum. Our findings reveal that western Eurasian genetic signatures in modern-day Native Americans derive not only from post-Columbian admixture, as commonly thought, but also from a mixed ancestry of the First Americans....

  7. Core-level photoemission revealing the Mott transition

    International Nuclear Information System (INIS)

    Kim, Hyeong-Do; Noh, Han-Jin; Kim, K.H.; Oh, S.-J.

    2005-01-01

    Ru 3d core-level X-ray photoemission spectra of various ruthenates are examined. They show in general two-peak structures, which can be assigned as the screened and unscreened peaks. The screened peak is absent in a Mott insulator, but develops into a main peak as the correlation strength becomes weak. This spectral behavior is well explained by the dynamical mean-field theory calculation for the single-band Hubbard model with the on-site core-hole potential using the exact diagonalization method. The new mechanism of the core-level photoemission satellite can be utilized to reveal the Mott transition phenomenon in various strongly correlated electron systems

  8. Revealing Tripartite Quantum Discord with Tripartite Information Diagram

    Directory of Open Access Journals (Sweden)

    Wei-Ting Lee

    2017-11-01

    Full Text Available A new measure based on the tripartite information diagram is proposed for identifying quantum discord in tripartite systems. The proposed measure generalizes the mutual information underlying discord from bipartite to tripartite systems, and utilizes both one-particle and two-particle projective measurements to reveal the characteristics of the tripartite quantum discord. The feasibility of the proposed measure is demonstrated by evaluating the tripartite quantum discord for systems with states close to Greenberger–Horne–Zeilinger, W, and biseparable states. In addition, the connections between tripartite quantum discord and two other quantum correlations—namely genuine tripartite entanglement and genuine tripartite Einstein–Podolsky–Rosen steering—are briefly discussed. The present study considers the case of quantum discord in tripartite systems. However, the proposed framework can be readily extended to general N-partite systems.

  9. Single Turnover at Molecular Polymerization Catalysts Reveals Spatiotemporally Resolved Reactions.

    Science.gov (United States)

    Easter, Quinn T; Blum, Suzanne A

    2017-10-23

    Multiple active individual molecular ruthenium catalysts have been pinpointed within growing polynorbornene, thereby revealing information on the reaction dynamics and location that is unavailable through traditional ensemble experiments. This is the first single-turnover imaging of a molecular catalyst by fluorescence microscopy and allows detection of individual monomer reactions at an industrially important molecular ruthenium ring-opening metathesis polymerization (ROMP) catalyst under synthetically relevant conditions (e.g. unmodified industrial catalyst, ambient pressure, condensed phase, ca. 0.03 m monomer). These results further establish the key fundamentals of this imaging technique for characterizing the reactivity and location of active molecular catalysts even when they are the minor components. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. ID-Check: Online Concealed Information Test Reveals True Identity.

    Science.gov (United States)

    Verschuere, Bruno; Kleinberg, Bennett

    2016-01-01

    The Internet has already changed people's lives considerably and is likely to drastically change forensic research. We developed a web-based test to reveal concealed autobiographical information. Initial studies identified a number of conditions that affect diagnostic efficiency. By combining these moderators, this study investigated the full potential of the online ID-check. Participants (n = 101) tried to hide their identity and claimed a false identity in a reaction time-based Concealed Information Test. Half of the participants were presented with personal details (e.g., first name, last name, birthday), whereas the others only saw irrelevant details. Results showed that participants' true identity could be detected with high accuracy (AUC = 0.98; overall accuracy: 86-94%). Online memory detection can reliably and validly detect whether someone is hiding their true identity. This suggests that online memory detection might become a valuable tool for forensic applications. © 2015 American Academy of Forensic Sciences.

  11. The ecological origins of snakes as revealed by skull evolution.

    Science.gov (United States)

    Da Silva, Filipe O; Fabre, Anne-Claire; Savriama, Yoland; Ollonen, Joni; Mahlow, Kristin; Herrel, Anthony; Müller, Johannes; Di-Poï, Nicolas

    2018-01-25

    The ecological origin of snakes remains amongst the most controversial topics in evolution, with three competing hypotheses: fossorial; marine; or terrestrial. Here we use a geometric morphometric approach integrating ecological, phylogenetic, paleontological, and developmental data for building models of skull shape and size evolution and developmental rate changes in squamates. Our large-scale data reveal that whereas the most recent common ancestor of crown snakes had a small skull with a shape undeniably adapted for fossoriality, all snakes plus their sister group derive from a surface-terrestrial form with non-fossorial behavior, thus redirecting the debate toward an underexplored evolutionary scenario. Our comprehensive heterochrony analyses further indicate that snakes later evolved novel craniofacial specializations through global acceleration of skull development. These results highlight the importance of the interplay between natural selection and developmental processes in snake origin and diversification, leading first to invasion of a new habitat and then to subsequent ecological radiations.

  12. Inheritance Patterns in Citation Networks Reveal Scientific Memes

    Directory of Open Access Journals (Sweden)

    Tobias Kuhn

    2014-11-01

    Full Text Available Memes are the cultural equivalent of genes that spread across human culture by means of imitation. What makes a meme and what distinguishes it from other forms of information, however, is still poorly understood. Our analysis of memes in the scientific literature reveals that they are governed by a surprisingly simple relationship between frequency of occurrence and the degree to which they propagate along the citation graph. We propose a simple formalization of this pattern and validate it with data from close to 50 million publication records from the Web of Science, PubMed Central, and the American Physical Society. Evaluations relying on human annotators, citation network randomizations, and comparisons with several alternative approaches confirm that our formula is accurate and effective, without a dependence on linguistic or ontological knowledge and without the application of arbitrary thresholds or filters.

  13. Inheritance Patterns in Citation Networks Reveal Scientific Memes

    Science.gov (United States)

    Kuhn, Tobias; Perc, Matjaž; Helbing, Dirk

    2014-10-01

    Memes are the cultural equivalent of genes that spread across human culture by means of imitation. What makes a meme and what distinguishes it from other forms of information, however, is still poorly understood. Our analysis of memes in the scientific literature reveals that they are governed by a surprisingly simple relationship between frequency of occurrence and the degree to which they propagate along the citation graph. We propose a simple formalization of this pattern and validate it with data from close to 50 million publication records from the Web of Science, PubMed Central, and the American Physical Society. Evaluations relying on human annotators, citation network randomizations, and comparisons with several alternative approaches confirm that our formula is accurate and effective, without a dependence on linguistic or ontological knowledge and without the application of arbitrary thresholds or filters.

  14. Conformational changes in DNA gyrase revealed by limited proteolysis

    DEFF Research Database (Denmark)

    Kampranis, S C; Maxwell, A

    1998-01-01

    We have used limited proteolysis to identify conformational changes in DNA gyrase. Gyrase exhibits a proteolytic fingerprint dominated by two fragments, one of approximately 62 kDa, deriving from the A protein, and another of approximately 25 kDa from the B protein. Quinolone binding to the enzyme......-DNA intermediate by calcium ions does not reveal any protection, suggesting that the quinolone-induced conformational change is different from an "open-gate" state of the enzyme. A quinolone-resistant mutant of gyrase fails to give the characteristic quinolone-associated proteolytic signature. The ATP...... does not prevent dimerization since incubation of the enzyme-DNA complex with both ADPNP and quinolones gives rise to a complex whose proteolytic pattern retains the characteristic signature of dimerization but has lost the quinolone-induced protection. As a result, the quinolone-gyrase complex can...

  15. Transcriptomic variation in a coral reveals pathways of clonal organisation

    DEFF Research Database (Denmark)

    K Bay, Line; Nielsen, Henrik Bjørn; Jarmer, Hanne Østergaard

    2009-01-01

    A microarray study was undertaken to examine the potential for clonal gene expression variation in a branching reef building coral, Acropora millepora. The role of small-scale gradients in light and water flow was examined by comparing gene expression levels between branch elevation (tip and base......) and position (centre and edge) of replicate coral colonies (n=3). Analyses of variance revealed that almost 60% of variation in gene expression was present between colonies and 34 genes were considered differentially expressed between colonies (minimum P=6.5 x 10(-4)). These genes are associated with energy...... of corymbose-like branching coral colonies such as A. millepora. Four genes were differentially expressed between the tip and base of branches (P=3.239 x 10(-4)) and were associated with lysosome lipase activity and fluorescence, suggesting that branch tips may encounter higher pathogen loads or levels...

  16. CW EPR parameters reveal cytochrome P450 ligand binding modes.

    Science.gov (United States)

    Lockart, Molly M; Rodriguez, Carlo A; Atkins, William M; Bowman, Michael K

    2018-06-01

    Cytochrome P450 (CYP) monoxygenses utilize heme cofactors to catalyze oxidation reactions. They play a critical role in metabolism of many classes of drugs, are an attractive target for drug development, and mediate several prominent drug interactions. Many substrates and inhibitors alter the spin state of the ferric heme by displacing the heme's axial water ligand in the resting enzyme to yield a five-coordinate iron complex, or they replace the axial water to yield a nitrogen-ligated six-coordinate iron complex, which are traditionally assigned by UV-vis spectroscopy. However, crystal structures and recent pulsed electron paramagnetic resonance (EPR) studies find a few cases where molecules hydrogen bond to the axial water. The water-bridged drug-H 2 O-heme has UV-vis spectra similar to nitrogen-ligated, six-coordinate complexes, but are closer to "reverse type I" complexes described in older liteature. Here, pulsed and continuous wave (CW) EPR demonstrate that water-bridged complexes are remarkably common among a range of nitrogenous drugs or drug fragments that bind to CYP3A4 or CYP2C9. Principal component analysis reveals a distinct clustering of CW EPR spectral parameters for water-bridged complexes. CW EPR reveals heterogeneous mixtures of ligated states, including multiple directly-coordinated complexes and water-bridged complexes. These results suggest that water-bridged complexes are under-represented in CYP structural databases and can have energies similar to other ligation modes. The data indicates that water-bridged binding modes can be identified and distinguished from directly-coordinated binding by CW EPR. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Cyp1a reporter zebrafish reveals target tissues for dioxin

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kun-Hee [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Park, Hye-Jeong [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); Kim, Jin Hee [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Kim, Suhyun [Graduate School of Medicine, Korea University, Ansan (Korea, Republic of); Williams, Darren R. [New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju (Korea, Republic of); Kim, Myeong-Kyu [Department of Neurology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Jung, Young Do [Department of Biochemistry, Chonnam National University Medical School, Gwangju (Korea, Republic of); Teraoka, Hiroki [School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu (Japan); Park, Hae-Chul [Graduate School of Medicine, Korea University, Ansan (Korea, Republic of); Choy, Hyon E., E-mail: hyonchoy@chonnam.ac.kr [Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Shin, Boo Ahn, E-mail: bashin@chonnam.ac.kr [Department of Microbiology, Chonnam National University Medical School, Gwangju (Korea, Republic of); Choi, Seok-Yong, E-mail: zebrafish@chonnam.ac.kr [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); School of Biological Sciences and Technology, Chonnam National University, Gwangju (Korea, Republic of)

    2013-06-15

    Highlights: •2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic anthropogenic substance ever identified. •Transgenic cyp1a reporter zebrafish reveals target tissues for TCDD. •The retinal bipolar cells, otic vesicle, lateral line, pancreas, cloaca and pectoral fin bud are novel targets in zebrafish for TCDD. •Our findings will further understanding of human health risks by TCDD. -- Abstract: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the unintentional byproduct of various industrial processes, is classified as human carcinogen and could disrupt reproductive, developmental and endocrine systems. Induction of cyp1a1 is used as an indicator of TCDD exposure. We sought to determine tissues that are vulnerable to TCDD toxicity using a transgenic zebrafish (Danio rerio) model. We inserted a nuclear enhanced green fluorescent protein gene (EGFP) into the start codon of a zebrafish cyp1a gene in a fosmid clone using DNA recombineering. The resulting recombineered fosmid was then used to generate cyp1a reporter zebrafish, embryos of which were exposed to TCDD. Expression pattern of EGFP in the reporter zebrafish mirrored that of endogenous cyp1a mRNA. In addition, exposure of the embryos to TCDD at as low as 10 pM for 72 h, which does not elicit morphological abnormalities of embryos, markedly increased GFP expression. Furthermore, the reporter embryos responded to other AhR ligands as well. Exposure of the embryos to TCDD revealed previously reported (the cardiovascular system, liver, pancreas, kidney, swim bladder and skin) and unreported target tissues (retinal bipolar cells, otic vesicle, lateral line, cloaca and pectoral fin bud) for TCDD. Transgenic cyp1a reporter zebrafish we have developed can further understanding of ecotoxicological relevance and human health risks by TCDD. In addition, they could be used to identify agonists of AhR and antidotes to TCDD toxicity.

  18. Eye movement monitoring reveals differential influences of emotion on memory

    Directory of Open Access Journals (Sweden)

    Lily Riggs

    2010-11-01

    Full Text Available Research shows that memory for emotional aspects of an event may be enhanced at the cost of impaired memory for surrounding peripheral details. However, this has only been assessed directly via verbal reports which reveal the outcome of a long stream of processing but cannot shed light on how/when emotion may affect the retrieval process. In the present experiment, eye movement monitoring was used as an indirect measure of memory as it can reveal aspects of online memory processing. For example, do emotions modulate the nature of memory representations or the speed with which such memories can be accessed? Participants viewed central negative and neutral scenes surrounded by three neutral objects and after a brief delay, memory was assessed indirectly via eye movement monitoring and then directly via verbal reports. Consistent with the previous literature, emotion enhanced central and impaired peripheral memory as indexed by eye movement scanning and verbal reports. This suggests that eye movement scanning may contribute and/or is related to conscious access of memory. However, the central/peripheral tradeoff effect was not observed in an early measure of eye movement behavior, i.e. participants were faster to orient to a critical region of change in the periphery irrespective of whether it was previously studied in a negative or neutral context. These findings demonstrate emotion’s differential influences on different aspects of retrieval. In particular, emotion appears to affect the detail within, and/or the evaluation of, stored memory representations, but it may not affect the initial access to those representations.

  19. A Network Based Methodology to Reveal Patterns in Knowledge Transfer

    Directory of Open Access Journals (Sweden)

    Orlando López-Cruz

    2015-12-01

    Full Text Available This paper motivates, presents and demonstrates in use a methodology based in complex network analysis to support research aimed at identification of sources in the process of knowledge transfer at the interorganizational level. The importance of this methodology is that it states a unified model to reveal knowledge sharing patterns and to compare results from multiple researches on data from different periods of time and different sectors of the economy. This methodology does not address the underlying statistical processes. To do this, national statistics departments (NSD provide documents and tools at their websites. But this proposal provides a guide to model information inferences gathered from data processing revealing links between sources and recipients of knowledge being transferred and that the recipient detects as main source to new knowledge creation. Some national statistics departments set as objective for these surveys the characterization of innovation dynamics in firms and to analyze the use of public support instruments. From this characterization scholars conduct different researches. Measures of dimensions of the network composed by manufacturing firms and other organizations conform the base to inquiry the structure that emerges from taking ideas from other organizations to incept innovations. These two sets of data are actors of a two- mode-network. The link between two actors (network nodes, one acting as the source of the idea. The second one acting as the destination comes from organizations or events organized by organizations that “provide” ideas to other group of firms. The resulting demonstrated design satisfies the objective of being a methodological model to identify sources in knowledge transfer of knowledge effectively used in innovation.

  20. Vibrio cholerae classical biotype strains reveal distinct signatures in Mexico.

    Science.gov (United States)

    Alam, Munirul; Islam, M Tarequl; Rashed, Shah Manzur; Johura, Fatema-tuz; Bhuiyan, Nurul A; Delgado, Gabriela; Morales, Rosario; Mendez, Jose Luis; Navarro, Armando; Watanabe, Haruo; Hasan, Nur-A; Colwell, Rita R; Cravioto, Alejandro

    2012-07-01

    Vibrio cholerae O1 classical (CL) biotype caused the fifth and sixth pandemics, and probably the earlier cholera pandemics, before the El Tor (ET) biotype initiated the seventh pandemic in Asia in the 1970s by completely displacing the CL biotype. Although the CL biotype was thought to be extinct in Asia and although it had never been reported from Latin America, V. cholerae CL and ET biotypes, including a hybrid ET, were found associated with areas of cholera endemicity in Mexico between 1991 and 1997. In this study, CL biotype strains isolated from areas of cholera endemicity in Mexico between 1983 and 1997 were characterized in terms of major phenotypic and genetic traits and compared with CL biotype strains isolated in Bangladesh between 1962 and 1989. According to sero- and biotyping data, all V. cholerae strains tested had the major phenotypic and genotypic characteristics specific for the CL biotype. Antibiograms revealed the majority of the Bangladeshi strains to be resistant to trimethoprim-sulfamethoxazole, furazolidone, ampicillin, and gentamicin, while the Mexican strains were sensitive to all of these drugs, as well as to ciprofloxacin, erythromycin, and tetracycline. Pulsed-field gel electrophoresis (PFGE) of NotI-digested genomic DNA revealed characteristic banding patterns for all of the CL biotype strains although the Mexican strains differed from the Bangladeshi strains in 1 to 2 DNA bands. The difference was subtle but consistent, as confirmed by the subclustering patterns in the PFGE-based dendrogram, and can serve as a regional signature, suggesting the pre-1991 existence and evolution of the CL biotype strains in the Americas, independent from Asia.

  1. Comparative Genomics Reveals High Genomic Diversity in the Genus Photobacterium.

    Science.gov (United States)

    Machado, Henrique; Gram, Lone

    2017-01-01

    Vibrionaceae is a large marine bacterial family, which can constitute up to 50% of the prokaryotic population in marine waters. Photobacterium is the second largest genus in the family and we used comparative genomics on 35 strains representing 16 of the 28 species described so far, to understand the genomic diversity present in the Photobacterium genus. Such understanding is important for ecophysiology studies of the genus. We used whole genome sequences to evaluate phylogenetic relationships using several analyses (16S rRNA, MLSA, fur , amino-acid usage, ANI), which allowed us to identify two misidentified strains. Genome analyses also revealed occurrence of higher and lower GC content clades, correlating with phylogenetic clusters. Pan- and core-genome analysis revealed the conservation of 25% of the genome throughout the genus, with a large and open pan-genome. The major source of genomic diversity could be traced to the smaller chromosome and plasmids. Several of the physiological traits studied in the genus did not correlate with phylogenetic data. Since horizontal gene transfer (HGT) is often suggested as a source of genetic diversity and a potential driver of genomic evolution in bacterial species, we looked into evidence of such in Photobacterium genomes. Genomic islands were the source of genomic differences between strains of the same species. Also, we found transposase genes and CRISPR arrays that suggest multiple encounters with foreign DNA. Presence of genomic exchange traits was widespread and abundant in the genus, suggesting a role in genomic evolution. The high genetic variability and indications of genetic exchange make it difficult to elucidate genome evolutionary paths and raise the awareness of the roles of foreign DNA in the genomic evolution of environmental organisms.

  2. Four not six: Revealing culturally common facial expressions of emotion.

    Science.gov (United States)

    Jack, Rachael E; Sun, Wei; Delis, Ioannis; Garrod, Oliver G B; Schyns, Philippe G

    2016-06-01

    As a highly social species, humans generate complex facial expressions to communicate a diverse range of emotions. Since Darwin's work, identifying among these complex patterns which are common across cultures and which are culture-specific has remained a central question in psychology, anthropology, philosophy, and more recently machine vision and social robotics. Classic approaches to addressing this question typically tested the cross-cultural recognition of theoretically motivated facial expressions representing 6 emotions, and reported universality. Yet, variable recognition accuracy across cultures suggests a narrower cross-cultural communication supported by sets of simpler expressive patterns embedded in more complex facial expressions. We explore this hypothesis by modeling the facial expressions of over 60 emotions across 2 cultures, and segregating out the latent expressive patterns. Using a multidisciplinary approach, we first map the conceptual organization of a broad spectrum of emotion words by building semantic networks in 2 cultures. For each emotion word in each culture, we then model and validate its corresponding dynamic facial expression, producing over 60 culturally valid facial expression models. We then apply to the pooled models a multivariate data reduction technique, revealing 4 latent and culturally common facial expression patterns that each communicates specific combinations of valence, arousal, and dominance. We then reveal the face movements that accentuate each latent expressive pattern to create complex facial expressions. Our data questions the widely held view that 6 facial expression patterns are universal, instead suggesting 4 latent expressive patterns with direct implications for emotion communication, social psychology, cognitive neuroscience, and social robotics. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  3. Compartmentation of glycogen metabolism revealed from 13C isotopologue distributions

    Directory of Open Access Journals (Sweden)

    Marin de Mas Igor

    2011-10-01

    Full Text Available Abstract Background Stable isotope tracers are used to assess metabolic flux profiles in living cells. The existing methods of measurement average out the isotopic isomer distribution in metabolites throughout the cell, whereas the knowledge of compartmental organization of analyzed pathways is crucial for the evaluation of true fluxes. That is why we accepted a challenge to create a software tool that allows deciphering the compartmentation of metabolites based on the analysis of average isotopic isomer distribution. Results The software Isodyn, which simulates the dynamics of isotopic isomer distribution in central metabolic pathways, was supplemented by algorithms facilitating the transition between various analyzed metabolic schemes, and by the tools for model discrimination. It simulated 13C isotope distributions in glucose, lactate, glutamate and glycogen, measured by mass spectrometry after incubation of hepatocytes in the presence of only labeled glucose or glucose and lactate together (with label either in glucose or lactate. The simulations assumed either a single intracellular hexose phosphate pool, or also channeling of hexose phosphates resulting in a different isotopic composition of glycogen. Model discrimination test was applied to check the consistency of both models with experimental data. Metabolic flux profiles, evaluated with the accepted model that assumes channeling, revealed the range of changes in metabolic fluxes in liver cells. Conclusions The analysis of compartmentation of metabolic networks based on the measured 13C distribution was included in Isodyn as a routine procedure. The advantage of this implementation is that, being a part of evaluation of metabolic fluxes, it does not require additional experiments to study metabolic compartmentation. The analysis of experimental data revealed that the distribution of measured 13C-labeled glucose metabolites is inconsistent with the idea of perfect mixing of hexose

  4. Architecture of cognitive flexibility revealed by lesion mapping

    Science.gov (United States)

    Barbey, Aron K.; Colom, Roberto; Grafman, Jordan

    2013-01-01

    Neuroscience has made remarkable progress in understanding the architecture of human intelligence, identifying a distributed network of brain structures that support goal-directed, intelligent behavior. However, the neural foundations of cognitive flexibility and adaptive aspects of intellectual function remain to be well characterized. Here, we report a human lesion study (n = 149) that investigates the neural bases of key competencies of cognitive flexibility (i.e., mental flexibility and the fluent generation of new ideas) and systematically examine their contributions to a broad spectrum of cognitive and social processes, including psychometric intelligence (Wechsler Adult Intelligence Scale), emotional intelligence (Mayer, Salovey, Caruso Emotional Intelligence Test), and personality (Neuroticism–Extraversion–Openness Personality Inventory). Latent variable modeling was applied to obtain error-free indices of each factor, followed by voxel-based lesion-symptom mapping to elucidate their neural substrates. Regression analyses revealed that latent scores for psychometric intelligence reliably predict latent scores for cognitive flexibility (adjusted R2 = 0.94). Lesion mapping results further indicated that these convergent processes depend on a shared network of frontal, temporal, and parietal regions, including white matter association tracts, which bind these areas into an integrated system. A targeted analysis of the unique variance explained by cognitive flexibility further revealed selective damage within the right superior temporal gyrus, a region known to support insight and the recognition of novel semantic relations. The observed findings motivate an integrative framework for understanding the neural foundations of adaptive behavior, suggesting that core elements of cognitive flexibility emerge from a distributed network of brain regions that support specific competencies for human intelligence. PMID:23721727

  5. Impaired Phosphate Tolerance Revealed With an Acute Oral Challenge.

    Science.gov (United States)

    Turner, Mandy E; White, Christine A; Hopman, Wilma M; Ward, Emilie C; Jeronimo, Paul S; Adams, Michael A; Holden, Rachel M

    2018-01-01

    Elevated serum phosphate is consistently linked with cardiovascular disease (CVD) events and mortality in the setting of normal and impaired kidney function. However, serum phosphate does not often exceed the upper limit of normal until glomerular filtration rate (GFR) falls below 30 mL/min/m 2 . It was hypothesized that the response to an oral, bioavailable phosphate load will unmask impaired phosphate tolerance, a maladaptation not revealed by baseline serum phosphate concentrations. In this study, rats with varying kidney function as well as normo-phosphatemic human subjects, with inulin-measured GFR (13.2 to 128.3mL/min), received an oral phosphate load. Hormonal and urinary responses were evaluated over 2 hours. Results revealed that the more rapid elevation of serum phosphate was associated with subjects and rats with higher levels of kidney function, greater responsiveness to acute changes in parathyroid hormone (PTH), and significantly more urinary phosphate at 2 hours. In humans, increases in urinary phosphate to creatinine ratio did not correlate with baseline serum phosphate concentrations but did correlate strongly to early increase of serum phosphate. The blunted rise in serum phosphate in rats with CKD was not the result of altered absorption. This result suggests acute tissue deposition may be altered in the setting of kidney function impairment. Early recognition of impaired phosphate tolerance could translate to important interventions, such as dietary phosphate restriction or phosphate binders, being initiated at much higher levels of kidney function than is current practice. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

  6. Control rod

    International Nuclear Information System (INIS)

    Igarashi, Takao; Sugawara, Satoshi; Yoshimoto, Yuichiro; Saito, Shozo; Fukumoto, Takashi.

    1987-01-01

    Purpose: To reduce the weight and thereby obtain satisfactory operationability of control rods by combining absorbing nuclear chain type neutron absorbers and conventional type neutron absorbers in the axial direction of blades. Constitution: Neutron absorber rods and long life type neutron absorber rods are disposed in a tie rod and a sheath. The neutron absorber rod comprises a poison tube made of stainless steels and packed with B 4 C powder. The long life type neutron absorber rod is prepared by packing B-10 enriched boron carbide powder into a hafnium metal rod, hafnium pipe, europium and stainless made poison tube. Since the long life type absorber rod uses HF as the absorbing nuclear chain type neutron absorber, it absorbs neutrons to form new neutron absorbers to increase the nuclear life. (Yoshino, Y.)

  7. Control Valve

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Wayne R.

    2018-03-20

    A control valve includes a first conduit having a first inlet and a first outlet and defining a first passage; a second conduit having a second inlet and a second outlet and defining a second passage, the second conduit extending into the first passage such that the second inlet is located within the first passage; and a valve plate disposed pivotably within the first passage, the valve plate defining a valve plate surface. Pivoting of the valve plate within the first passage varies flow from the first inlet to the first outlet and the valve plate is pivotal between a first position and a second position such that in the first position the valve plate substantially prevents fluid communication between the first passage and the second passage and such that in the second position the valve plate permits fluid communication between the first passage and the second passage.

  8. Control Prenatal

    Directory of Open Access Journals (Sweden)

    P. Susana Aguilera, DRA.

    2014-11-01

    Full Text Available Los principales objetivos del control prenatal son identificar aquellos pacientes de mayor riesgo, con el fin de realizar intervenciones en forma oportuna que permitan prevenir dichos riesgos y así lograr un buen resultado perinatal. Esto se realiza a través de la historia médica y reproductiva de la mujer, el examen físico, la realización de algunos exámenes de laboratorio y exámenes de ultrasonido. Además es importante promover estilos de vida saludables, la suplementación de ácido fólico, una consejería nutricional y educación al respecto.

  9. Novel Polyurethane Matrix Systems Reveal a Particular Sustained Release Behavior Studied by Imaging and Computational Modeling.

    Science.gov (United States)

    Campiñez, María Dolores; Caraballo, Isidoro; Puchkov, Maxim; Kuentz, Martin

    2017-07-01

    The aim of the present work was to better understand the drug-release mechanism from sustained release matrices prepared with two new polyurethanes, using a novel in silico formulation tool based on 3-dimensional cellular automata. For this purpose, two polymers and theophylline as model drug were used to prepare binary matrix tablets. Each formulation was simulated in silico, and its release behavior was compared to the experimental drug release profiles. Furthermore, the polymer distributions in the tablets were imaged by scanning electron microscopy (SEM) and the changes produced by the tortuosity were quantified and verified using experimental data. The obtained results showed that the polymers exhibited a surprisingly high ability for controlling drug release at low excipient concentrations (only 10% w/w of excipient controlled the release of drug during almost 8 h). The mesoscopic in silico model helped to reveal how the novel biopolymers were controlling drug release. The mechanism was found to be a special geometrical arrangement of the excipient particles, creating an almost continuous barrier surrounding the drug in a very effective way, comparable to lipid or waxy excipients but with the advantages of a much higher compactability, stability, and absence of excipient polymorphism.

  10. Directional biases reveal utilization of arm's biomechanical properties for optimization of motor behavior.

    Science.gov (United States)

    Goble, Jacob A; Zhang, Yanxin; Shimansky, Yury; Sharma, Siddharth; Dounskaia, Natalia V

    2007-09-01

    Strategies used by the CNS to optimize arm movements in terms of speed, accuracy, and resistance to fatigue remain largely unknown. A hypothesis is studied that the CNS exploits biomechanical properties of multijoint limbs to increase efficiency of movement control. To test this notion, a novel free-stroke drawing task was used that instructs subjects to make straight strokes in as many different directions as possible in the horizontal plane through rotations of the elbow and shoulder joints. Despite explicit instructions to distribute strokes uniformly, subjects showed biases to move in specific directions. These biases were associated with a tendency to perform movements that included active motion at one joint and largely passive motion at the other joint, revealing a tendency to minimize intervention of muscle torque for regulation of the effect of interaction torque. Other biomechanical factors, such as inertial resistance and kinematic manipulability, were unable to adequately account for these significant biases. Also, minimizations of jerk, muscle torque change, and sum of squared muscle torque were analyzed; however, these cost functions failed to explain the observed directional biases. Collectively, these results suggest that knowledge of biomechanical cost functions regarding interaction torque (IT) regulation is available to the control system. This knowledge may be used to evaluate potential movements and to select movement of "low cost." The preference to reduce active regulation of interaction torque suggests that, in addition to muscle energy, the criterion for movement cost may include neural activity required for movement control.

  11. Rapid Presentation of Emotional Expressions Reveals New Emotional Impairments in Tourette’s Syndrome

    Directory of Open Access Journals (Sweden)

    Martial eMermillod

    2013-04-01

    Full Text Available Objective:Based on a variety of empirical evidence obtained within the theoretical framework of embodiment theory, we considered it likely that motor disorders in Tourette’s syndrome (TS would have emotional consequences for TS patients. However, previous research using emotional facial categorization tasks suggests that these consequences are limited to TS patients with obsessive-compulsive behaviors(OCB.Method:These studies used long stimulus presentations which allowed the participants to categorize the different emotional facial expressions (EFEs on the basis of a perceptual analysis that might potentially hide a lack of emotional feeling for certain emotions. In order to reduce this perceptual bias, we used a rapid visual presentation procedure.Results:Using this new experimental method, we revealed different and surprising impairments on several EFEs in TS patients compared to matched healthy control participants. Moreover, a spatial frequency analysis of the visual signal processed by the patients suggests that these impairments may be located at a cortical level.Conclusions:The current study indicates that the rapid visual presentation paradigm makes it possible to identify various potential emotional disorders that were not revealed by the standard visual presentation procedures previously reported in the literature. Moreover, the spatial frequency analysis performed in our study suggests that emotional deficit in TS might lie at the level of temporal cortical areas dedicated to the processing of HSF visual information.

  12. Comparison of S. cerevisiae F-BAR domain structures reveals a conserved inositol phosphate binding site

    Science.gov (United States)

    Moravcevic, Katarina; Alvarado, Diego; Schmitz, Karl R.; Kenniston, Jon A.; Mendrola, Jeannine M.; Ferguson, Kathryn M.; Lemmon, Mark A.

    2015-01-01

    SUMMARY F-BAR domains control membrane interactions in endocytosis, cytokinesis, and cell signaling. Although generally thought to bind curved membranes containing negatively charged phospholipids, numerous functional studies argue that differences in lipid-binding selectivities of F-BAR domains are functionally important. Here, we compare membrane-binding properties of the S. cerevisiae F-BAR domains in vitro and in vivo. Whereas some F-BAR domains (such as Bzz1p and Hof1p F-BARs) bind equally well to all phospholipids, the F-BAR domain from the RhoGAP Rgd1p preferentially binds phosphoinositides. We determined X-ray crystal structures of F-BAR domains from Hof1p and Rgd1p, the latter bound to an inositol phosphate. The structures explain phospholipid-binding selectivity differences, and reveal an F-BAR phosphoinositide binding site that is fully conserved in a mammalian RhoGAP called Gmip, and is partly retained in certain other F-BAR domains. Our findings reveal previously unappreciated determinants of F-BAR domain lipid-binding specificity, and provide a basis for its prediction from sequence. PMID:25620000

  13. Transcriptome Sequencing Revealed Significant Alteration of Cortical Promoter Usage and Splicing in Schizophrenia

    Science.gov (United States)

    Wu, Jing Qin; Wang, Xi; Beveridge, Natalie J.; Tooney, Paul A.; Scott, Rodney J.; Carr, Vaughan J.; Cairns, Murray J.

    2012-01-01

    Background While hybridization based analysis of the cortical transcriptome has provided important insight into the neuropathology of schizophrenia, it represents a restricted view of disease-associated gene activity based on predetermined probes. By contrast, sequencing technology can provide un-biased analysis of transcription at nucleotide resolution. Here we use this approach to investigate schizophrenia-associated cortical gene expression. Methodology/Principal Findings The data was generated from 76 bp reads of RNA-Seq, aligned to the reference genome and assembled into transcripts for quantification of exons, splice variants and alternative promoters in postmortem superior temporal gyrus (STG/BA22) from 9 male subjects with schizophrenia and 9 matched non-psychiatric controls. Differentially expressed genes were then subjected to further sequence and functional group analysis. The output, amounting to more than 38 Gb of sequence, revealed significant alteration of gene expression including many previously shown to be associated with schizophrenia. Gene ontology enrichment analysis followed by functional map construction identified three functional clusters highly relevant to schizophrenia including neurotransmission related functions, synaptic vesicle trafficking, and neural development. Significantly, more than 2000 genes displayed schizophrenia-associated alternative promoter usage and more than 1000 genes showed differential splicing (FDRschizophrenia-associated transcriptional diversity within the STG, and revealed variants with important implications for the complex pathophysiology of schizophrenia. PMID:22558445

  14. Physiological and Proteomics Analyses Reveal Low-Phosphorus Stress Affected the Regulation of Photosynthesis in Soybean.

    Science.gov (United States)

    Chu, Shanshan; Li, Hongyan; Zhang, Xiangqian; Yu, Kaiye; Chao, Maoni; Han, Suoyi; Zhang, Dan

    2018-06-06

    Previous studies have revealed a significant genetic relationship between phosphorus (P)-efficiency and photosynthesis-related traits in soybean. In this study, we used proteome profiling in combination with expression analysis, biochemical investigations, and leaf ultrastructural analysis to identify the underlying physiological and molecular responses. The expression analysis and ultrastructural analysis showed that the photosynthesis key genes were decreased at transcript levels and the leaf mesophyll and chloroplast were severely damaged after low-P stress. Approximately 55 protein spots showed changes under low-P condition by mass spectrometry, of which 17 were involved in various photosynthetic processes. Further analysis revealed the depression of photosynthesis caused by low-P stress mainly involves the regulation of leaf structure, adenosine triphosphate (ATP) synthesis, absorption and transportation of CO₂, photosynthetic electron transport, production of assimilatory power, and levels of enzymes related to the Calvin cycle. In summary, our findings indicated that the existence of a stringent relationship between P supply and the genomic control of photosynthesis in soybean. As an important strategy to protect soybean photosynthesis, P could maintain the stability of cell structure, up-regulate the enzymes’ activities, recover the process of photosystem II (PSII), and induce the expression of low-P responsive genes and proteins.

  15. Comparative Circadian Metabolomics Reveal Differential Effects of Nutritional Challenge in the Serum and Liver.

    Science.gov (United States)

    Abbondante, Serena; Eckel-Mahan, Kristin L; Ceglia, Nicholas J; Baldi, Pierre; Sassone-Corsi, Paolo

    2016-02-05

    Diagnosis and therapeutic interventions in pathological conditions rely upon clinical monitoring of key metabolites in the serum. Recent studies show that a wide range of metabolic pathways are controlled by circadian rhythms whose oscillation is affected by nutritional challenges, underscoring the importance of assessing a temporal window for clinical testing and thereby questioning the accuracy of the reading of critical pathological markers in circulation. We have been interested in studying the communication between peripheral tissues under metabolic homeostasis perturbation. Here we present a comparative circadian metabolomic analysis on serum and liver in mice under high fat diet. Our data reveal that the nutritional challenge induces a loss of serum metabolite rhythmicity compared with liver, indicating a circadian misalignment between the tissues analyzed. Importantly, our results show that the levels of serum metabolites do not reflect the circadian liver metabolic signature or the effect of nutritional challenge. This notion reveals the possibility that misleading reads of metabolites in circulation may result in misdiagnosis and improper treatments. Our findings also demonstrate a tissue-specific and time-dependent disruption of metabolic homeostasis in response to altered nutrition. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Voxel-based MRI intensitometry reveals extent of cerebral white matter pathology in amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Viktor Hartung

    Full Text Available Amyotrophic lateral sclerosis (ALS is characterized by progressive loss of upper and lower motor neurons. Advanced MRI techniques such as diffusion tensor imaging have shown great potential in capturing a common white matter pathology. However the sensitivity is variable and diffusion tensor imaging is not yet applicable to the routine clinical environment. Voxel-based morphometry (VBM has revealed grey matter changes in ALS, but the bias-reducing algorithms inherent to traditional VBM are not optimized for the assessment of the white matter changes. We have developed a novel approach to white matter analysis, namely voxel-based intensitometry (VBI. High resolution T1-weighted MRI was acquired at 1.5 Tesla in 30 ALS patients and 37 age-matched healthy controls. VBI analysis at the group level revealed widespread white matter intensity increases in the corticospinal tracts, corpus callosum, sub-central, frontal and occipital white matter tracts and cerebellum. VBI results correlated with disease severity (ALSFRS-R and patterns of cerebral involvement differed between bulbar- and limb-onset. VBI would be easily translatable to the routine clinical environment, and once optimized for individual analysis offers significant biomarker potential in ALS.

  17. Altered brain structural networks in attention deficit/hyperactivity disorder children revealed by cortical thickness.

    Science.gov (United States)

    Liu, Tian; Chen, Yanni; Li, Chenxi; Li, Youjun; Wang, Jue

    2017-07-04

    This study investigated the cortical thickness and topological features of human brain anatomical networks related to attention deficit/hyperactivity disorder. Data were collected from 40 attention deficit/hyperactivity disorder children and 40 normal control children. Interregional correlation matrices were established by calculating the correlations of cortical thickness between all pairs of cortical regions (68 regions) of the whole brain. Further thresholds were applied to create binary matrices to construct a series of undirected and unweighted graphs, and global, local, and nodal efficiencies were computed as a function of the network cost. These experimental results revealed abnormal cortical thickness and correlations in attention deficit/hyperactivity disorder, and showed that the brain structural networks of attention deficit/hyperactivity disorder subjects had inefficient small-world topological features. Furthermore, their topological properties were altered abnormally. In particular, decreased global efficiency combined with increased local efficiency in attention deficit/hyperactivity disorder children led to a disorder-related shift of the network topological structure toward regular networks. In addition, nodal efficiency, cortical thickness, and correlation analyses revealed that several brain regions were altered in attention deficit/hyperactivity disorder patients. These findings are in accordance with a hypothesis of dysfunctional integration and segregation of the brain in patients with attention deficit/hyperactivity disorder and provide further evidence of brain dysfunction in attention deficit/hyperactivity disorder patients by observing cortical thickness on magnetic resonance imaging.

  18. Evolutionary Meta-Analysis of Association Studies Reveals Ancient Constraints Affecting Disease Marker Discovery

    Science.gov (United States)

    Dudley, Joel T.; Chen, Rong; Sanderford, Maxwell; Butte, Atul J.; Kumar, Sudhir

    2012-01-01

    Genome-wide disease association studies contrast genetic variation between disease cohorts and healthy populations to discover single nucleotide polymorphisms (SNPs) and other genetic markers revealing underlying genetic architectures of human diseases. Despite scores of efforts over the past decade, many reproducible genetic variants that explain substantial proportions of the heritable risk of common human diseases remain undiscovered. We have conducted a multispecies genomic analysis of 5,831 putative human risk variants for more than 230 disease phenotypes reported in 2,021 studies. We find that the current approaches show a propensity for discovering disease-associated SNPs (dSNPs) at conserved genomic positions because the effect size (odds ratio) and allelic P value of genetic association of an SNP relates strongly to the evolutionary conservation of their genomic position. We propose a new measure for ranking SNPs that integrates evolutionary conservation scores and the P value (E-rank). Using published data from a large case-control study, we demonstrate that E-rank method prioritizes SNPs with a greater likelihood of bona fide and reproducible genetic disease associations, many of which may explain greater proportions of genetic variance. Therefore, long-term evolutionary histories of genomic positions offer key practical utility in reassessing data from existing disease association studies, and in the design and analysis of future studies aimed at revealing the genetic basis of common human diseases. PMID:22389448

  19. Live cell imaging reveals marked variability in myoblast proliferation and fate

    Science.gov (United States)

    2013-01-01

    Background During the process of muscle regeneration, activated stem cells termed satellite cells proliferate, and then differentiate to form new myofibers that restore the injured area. Yet not all satellite cells contribute to muscle repair. Some continue to proliferate, others die, and others become quiescent and are available for regeneration following subsequent injury. The mechanisms that regulate the adoption of different cell fates in a muscle cell precursor population remain unclear. Methods We have used live cell imaging and lineage tracing to study cell fate in the C2 myoblast line. Results Analyzing the behavior of individual myoblasts revealed marked variability in both cell cycle duration and viability, but similarities between cells derived from the same parental lineage. As a consequence, lineage sizes and outcomes differed dramatically, and individual lineages made uneven contributions toward the terminally differentiated population. Thus, the cohort of myoblasts undergoing differentiation at the end of an experiment differed dramatically from the lineages present at the beginning. Treatment with IGF-I increased myoblast number by maintaining viability and by stimulating a fraction of cells to complete one additional cell cycle in differentiation medium, and as a consequence reduced the variability of the terminal population compared with controls. Conclusion Our results reveal that heterogeneity of responses to external cues is an intrinsic property of cultured myoblasts that may be explained in part by parental lineage, and demonstrate the power of live cell imaging for understanding how muscle differentiation is regulated. PMID:23638706

  20. Quantitative proteomics of the tonoplast reveals a role for glycolytic enzymes in salt tolerance.

    Science.gov (United States)

    Barkla, Bronwyn J; Vera-Estrella, Rosario; Hernández-Coronado, Marcela; Pantoja, Omar

    2009-12-01

    To examine the role of the tonoplast in plant salt tolerance and identify proteins involved in the regulation of transporters for vacuolar Na(+) sequestration, we exploited a targeted quantitative proteomics approach. Two-dimensional differential in-gel electrophoresis analysis of free flow zonal electrophoresis separated tonoplast fractions from control, and salt-treated Mesembryanthemum crystallinum plants revealed the membrane association of glycolytic enzymes aldolase and enolase, along with subunits of the vacuolar H(+)-ATPase V-ATPase. Protein blot analysis confirmed coordinated salt regulation of these proteins, and chaotrope treatment indicated a strong tonoplast association. Reciprocal coimmunoprecipitation studies revealed that the glycolytic enzymes interacted with the V-ATPase subunit B VHA-B, and aldolase was shown to stimulate V-ATPase activity in vitro by increasing the affinity for ATP. To investigate a physiological role for this association, the Arabidopsis thaliana cytoplasmic enolase mutant, los2, was characterized. These plants were salt sensitive, and there was a specific reduction in enolase abundance in the tonoplast from salt-treated plants. Moreover, tonoplast isolated from mutant plants showed an impaired ability for aldolase stimulation of V-ATPase hydrolytic activity. The association of glycolytic proteins with the tonoplast may not only channel ATP to the V-ATPase, but also directly upregulate H(+)-pump activity.

  1. Recent adaptive events in human brain revealed by meta-analysis of positively selected genes.

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    Yue Huang

    Full Text Available BACKGROUND AND OBJECTIVES: Analysis of positively-selected genes can help us understand how human evolved, especially the evolution of highly developed cognitive functions. However, previous works have reached conflicting conclusions regarding whether human neuronal genes are over-represented among genes under positive selection. METHODS AND RESULTS: We divided positively-selected genes into four groups according to the identification approaches, compiling a comprehensive list from 27 previous studies. We showed that genes that are highly expressed in the central nervous system are enriched in recent positive selection events in human history identified by intra-species genomic scan, especially in brain regions related to cognitive functions. This pattern holds when different datasets, parameters and analysis pipelines were used. Functional category enrichment analysis supported these findings, showing that synapse-related functions are enriched in genes under recent positive selection. In contrast, immune-related functions, for instance, are enriched in genes under ancient positive selection revealed by inter-species coding region comparison. We further demonstrated that most of these patterns still hold even after controlling for genomic characteristics that might bias genome-wide identification of positively-selected genes including gene length, gene density, GC composition, and intensity of negative selection. CONCLUSION: Our rigorous analysis resolved previous conflicting conclusions and revealed recent adaptation of human brain functions.

  2. An Integrated Cell Purification and Genomics Strategy Reveals Multiple Regulators of Pancreas Development

    Science.gov (United States)

    Benitez, Cecil M.; Qu, Kun; Sugiyama, Takuya; Pauerstein, Philip T.; Liu, Yinghua; Tsai, Jennifer; Gu, Xueying; Ghodasara, Amar; Arda, H. Efsun; Zhang, Jiajing; Dekker, Joseph D.; Tucker, Haley O.; Chang, Howard Y.; Kim, Seung K.

    2014-01-01

    The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus. PMID:25330008

  3. An integrated cell purification and genomics strategy reveals multiple regulators of pancreas development.

    Directory of Open Access Journals (Sweden)

    Cecil M Benitez

    2014-10-01

    Full Text Available The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus.

  4. Astronomers Reveal Extinct Extra-Terrestrial Fusion Reactor

    Science.gov (United States)

    2004-06-01

    An international team of astronomers, studying the left-over remnants of stars like our own Sun, have found a remarkable object where the nuclear reactor that once powered it has only just shut down. This star, the hottest known white dwarf, H1504+65, seems to have been stripped of its entire outer regions during its death throes leaving behind the core that formed its power plant. Scientists from the United Kingdom, Germany and the USA focused two of NASA's space telescopes, the Chandra X-ray Observatory and the Far Ultraviolet Spectroscopic Explorer (FUSE), onto H1504+65 to probe its composition and measure its temperature. The data revealed that the stellar surface is extremely hot, 200,000 degrees, and is virtually free of hydrogen and helium, something never before observed in any star. Instead, the surface is composed mainly of carbon and oxygen, the 'ashes' of the fusion of helium in a nuclear reactor. An important question we must answer is why has this unique star lost the hydrogen and helium, which usually hide the stellar interior from our view? Professor Martin Barstow (University of Leicester) said. 'Studying the nature of the ashes of dead stars give us important clues as to how stars like the Sun live their lives and eventually die. The nuclear waste of carbon and oxygen produced in the process are essential elements for life and are eventually recycled into interstellar space to form new stars, planets and, possibly, living beings.' Professor Klaus Werner (University of Tübingen) said. 'We realized that this star has, on astronomical time scales, only very recently shut down nuclear fusion (about a hundred years ago). We clearly see the bare, now extinct reactor that once powered a bright giant star.' Dr Jeffrey Kruk (Johns Hopkins University) said: 'Astronomers have long predicted that many stars would have carbon-oxygen cores near the end of their lives, but I never expected we would actually be able to see one. This is a wonderful opportunity to

  5. Toward an implicit measure of emotions: ratings of abstract images reveal distinct emotional states.

    Science.gov (United States)

    Bartoszek, Gregory; Cervone, Daniel

    2017-11-01

    Although implicit tests of positive and negative affect exist, implicit measures of distinct emotional states are scarce. Three experiments examined whether a novel implicit emotion-assessment task, the rating of emotion expressed in abstract images, would reveal distinct emotional states. In Experiment 1, participants exposed to a sadness-inducing story inferred more sadness, and less happiness, in abstract images. In Experiment 2, an anger-provoking interaction increased anger ratings. In Experiment 3, compared to neutral images, spider images increased fear ratings in spider-fearful participants but not in controls. In each experiment, the implicit task indicated elevated levels of the target emotion and did not indicate elevated levels of non-target negative emotions; the task thus differentiated among emotional states of the same valence. Correlations also supported the convergent and discriminant validity of the implicit task. Supporting the possibility that heuristic processes underlie the ratings, group differences were stronger among those who responded relatively quickly.

  6. Revealing −1 Programmed Ribosomal Frameshifting Mechanisms by Single-Molecule Techniques and Computational Methods

    Directory of Open Access Journals (Sweden)

    Kai-Chun Chang

    2012-01-01

    Full Text Available Programmed ribosomal frameshifting (PRF serves as an intrinsic translational regulation mechanism employed by some viruses to control the ratio between structural and enzymatic proteins. Most viral mRNAs which use PRF adapt an H-type pseudoknot to stimulate −1 PRF. The relationship between the thermodynamic stability and the frameshifting efficiency of pseudoknots has not been fully understood. Recently, single-molecule force spectroscopy has revealed that the frequency of −1 PRF correlates with the unwinding forces required for disrupting pseudoknots, and that some of the unwinding work dissipates irreversibly due to the torsional restraint of pseudoknots. Complementary to single-molecule techniques, computational modeling provides insights into global motions of the ribosome, whose structural transitions during frameshifting have not yet been elucidated in atomic detail. Taken together, recent advances in biophysical tools may help to develop antiviral therapies that target the ubiquitous −1 PRF mechanism among viruses.

  7. Microstructure of atmospheric particles revealed by TXM and a new mode of influenza virus transmission

    Energy Technology Data Exchange (ETDEWEB)

    Bao, L.M., E-mail: baoliangman@sinap.ac.cn [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Zhang, G.L., E-mail: zhangguilin@sinap.ac.cn [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Lei, Q.T.; Li, Y.; Li, X.L. [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Hwu, Y.K. [Institute of Physics, Academia Sinica, Taipei 11529, Taiwan (China); Yi, J.M. [Advanced Photon Source, Argonne National Laboratory, Argonne 60439 (United States)

    2015-09-15

    For control of influenza, firstly it is important to find the real virus transmission media. Atmospheric aerosol particles are presumably one of the media. In this study, three typical atmospheric inhaled particles in Shanghai were studied by the synchrotron based transmission X-ray microscopes (TXM). Three dimensional microstructure of the particles reveals that there are many pores contained in, particularly the coal combustion fly particles which may be possible virus carrier. The particles can transport over long distance and cause long-range infections due to its light weight. We suggest a mode which is droplet combining with aerosol mode. By this mode the transmission of global and pandemic influenzas and infection between inland avian far from population and poultry or human living in cities along coast may be explained.

  8. Educational games for brain health: revealing their unexplored potential through a neurocognitive approach

    Directory of Open Access Journals (Sweden)

    Patrick eFissler

    2015-07-01

    Full Text Available Educational games link the motivational nature of games with learning of knowledge and skills. Here, we go beyond effects on these learning outcomes. We review two lines of evidence which indicate the currently unexplored potential of educational games to promote brain health: First, gaming with specific neurocognitive demands (e.g., executive control, and second, educational learning experiences (e.g., studying foreign languages improve brain health markers. These markers include cognitive ability, brain function, and brain structure. As educational games allow the combination of specific neurocognitive demands with educational learning experiences, they seem to be optimally suited for promoting brain health. We propose a neurocognitive approach to reveal this unexplored potential of educational games in future research.

  9. HPLC-MS-Based Metabonomics Reveals Disordered Lipid Metabolism in Patients with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Xinjie Zhao

    2011-12-01

    Full Text Available Ultra-high performance liquid chromatography/ quadrupole time of flight mass spectrometry-based metabonomics platform was employed to profile the plasma metabolites of patients with metabolic syndrome and the healthy controls. Data analysis revealed lots of differential metabolites between the two groups, and most of them were identified as lipids. Several fatty acids and lysophosphatidylcholines were of higher plasma levels in the patient group, indicating the occurrence of insulin resistance and inflammation. The identified ether phospholipids were decreased in the patient group, reflecting the oxidative stress and some metabolic disorders. These identified metabolites can also be used to aid diagnosis of patients with metabolic syndrome. These results showed that metabonomics was a promising and powerful method to study metabolic syndrome.

  10. Olig2 and Hes regulatory dynamics during motor neuron differentiation revealed by single cell transcriptomics.

    Directory of Open Access Journals (Sweden)

    Andreas Sagner

    2018-02-01

    Full Text Available During tissue development, multipotent progenitors differentiate into specific cell types in characteristic spatial and temporal patterns. We addressed the mechanism linking progenitor identity and differentiation rate in the neural tube, where motor neuron (MN progenitors differentiate more rapidly than other progenitors. Using single cell transcriptomics, we defined the transcriptional changes associated with the transition of neural progenitors into MNs. Reconstruction of gene expression dynamics from these data indicate a pivotal role for the MN determinant Olig2 just prior to MN differentiation. Olig2 represses expression of the Notch signaling pathway effectors Hes1 and Hes5. Olig2 repression of Hes5 appears to be direct, via a conserved regulatory element within the Hes5 locus that restricts expression from MN progenitors. These findings reveal a tight coupling between the regulatory networks that control patterning and neuronal differentiation and demonstrate how Olig2 acts as the developmental pacemaker coordinating the spatial and temporal pattern of MN generation.

  11. Plutella australiana (Lepidoptera, Plutellidae), an overlooked diamondback moth revealed by DNA barcodes

    Science.gov (United States)

    Landry, Jean-François; Hebert, Paul DN

    2013-01-01

    Abstract The genus Plutella was thought to be represented in Australia by a single introduced species, Plutella xylostella (Linnaeus), the diamondback moth. Its status as a major pest of cruciferous crops, and the difficulty in developing control strategies has motivated broad-ranging studies on its biology. Prior genetic work has generally supported the conclusion that populations of this migratory species are connected by substantial gene flow. However, the present study reveals the presence of two genetically divergent lineages of this taxonin Australia. One shows close genetic and morphological similarity with the nearly cosmopolitan Plutella xylostella. The second lineage possesses a similar external morphology, but marked sequence divergence in the barcode region of the cytochrome c oxidase I gene, coupled with clear differences in genitalia. As a consequence, members of this lineage are described as a new species, Plutella australiana Landry & Hebert, which is broadly distributed in the eastern half of Australia. PMID:24167421

  12. Automatic sleep classification using a data-driven topic model reveals latent sleep states

    DEFF Research Database (Denmark)

    Koch, Henriette; Christensen, Julie Anja Engelhard; Frandsen, Rune

    2014-01-01

    Latent Dirichlet Allocation. Model application was tested on control subjects and patients with periodic leg movements (PLM) representing a non-neurodegenerative group, and patients with idiopathic REM sleep behavior disorder (iRBD) and Parkinson's Disease (PD) representing a neurodegenerative group......Background: The golden standard for sleep classification uses manual scoring of polysomnography despite points of criticism such as oversimplification, low inter-rater reliability and the standard being designed on young and healthy subjects. New method: To meet the criticism and reveal the latent...... sleep states, this study developed a general and automatic sleep classifier using a data-driven approach. Spectral EEG and EOG measures and eye correlation in 1 s windows were calculated and each sleep epoch was expressed as a mixture of probabilities of latent sleep states by using the topic model...

  13. Inter-ring rotations of AAA ATPase p97 revealed by electron cryomicroscopy.

    Science.gov (United States)

    Yeung, Heidi O; Förster, Andreas; Bebeacua, Cecilia; Niwa, Hajime; Ewens, Caroline; McKeown, Ciarán; Zhang, Xiaodong; Freemont, Paul S

    2014-03-05

    The type II AAA+ protein p97 is involved in numerous cellular activities, including endoplasmic reticulum-associated degradation, transcription activation, membrane fusion and cell-cycle control. These activities are at least in part regulated by the ubiquitin system, in which p97 is thought to target ubiquitylated protein substrates within macromolecular complexes and assist in their extraction or disassembly. Although ATPase activity is essential for p97 function, little is known about how ATP binding or hydrolysis is coupled with p97 conformational changes and substrate remodelling. Here, we have used single-particle electron cryomicroscopy (cryo-EM) to study the effect of nucleotides on p97 conformation. We have identified conformational heterogeneity within the cryo-EM datasets from which we have resolved two major p97 conformations. A comparison of conformations reveals inter-ring rotations upon nucleotide binding and hydrolysis that may be linked to the remodelling of target protein complexes.

  14. Plutella australiana (Lepidoptera, Plutellidae), an overlooked diamondback moth revealed by DNA barcodes.

    Science.gov (United States)

    Landry, Jean-François; Hebert, Paul Dn

    2013-01-01

    The genus Plutella was thought to be represented in Australia by a single introduced species, Plutella xylostella (Linnaeus), the diamondback moth. Its status as a major pest of cruciferous crops, and the difficulty in developing control strategies has motivated broad-ranging studies on its biology. Prior genetic work has generally supported the conclusion that populations of this migratory species are connected by substantial gene flow. However, the present study reveals the presence of two genetically divergent lineages of this taxonin Australia. One shows close genetic and morphological similarity with the nearly cosmopolitan Plutella xylostella. The second lineage possesses a similar external morphology, but marked sequence divergence in the barcode region of the cytochrome c oxidase I gene, coupled with clear differences in genitalia. As a consequence, members of this lineage are described as a new species, Plutella australiana Landry & Hebert, which is broadly distributed in the eastern half of Australia.

  15. Biofilm growth program and architecture revealed by single-cell live imaging

    Science.gov (United States)

    Yan, Jing; Sabass, Benedikt; Stone, Howard; Wingreen, Ned; Bassler, Bonnie

    Biofilms are surface-associated bacterial communities. Little is known about biofilm structure at the level of individual cells. We image living, growing Vibrio cholerae biofilms from founder cells to ten thousand cells at single-cell resolution, and discover the forces underpinning the architectural evolution of the biofilm. Mutagenesis, matrix labeling, and simulations demonstrate that surface-adhesion-mediated compression causes V. cholerae biofilms to transition from a two-dimensional branched morphology to a dense, ordered three-dimensional cluster. We discover that directional proliferation of rod-shaped bacteria plays a dominant role in shaping the biofilm architecture, and this growth pattern is controlled by a single gene. Competition analyses reveal the advantages of the dense growth mode in providing the biofilm with superior mechanical properties. We will further present continuum theory to model the three-dimensional growth of biofilms at the solid-liquid interface as well as solid-air interface.

  16. Spaceflight Alters Bacterial Gene Expression and Virulence and Reveals Role for Global Regulator Hfq

    Science.gov (United States)

    Wilson, J. W.; Ott, C. M.; zuBentrup, K. Honer; Ramamurthy R.; Quick, L.; Porwollik, S.; Cheng, P.; McClellan, M.; Tsaprailis, G.; Radabaugh, T.; hide

    2007-01-01

    A comprehensive analysis of both the molecular genetic and phenotypic responses of any organism to the spaceflight environment has never been accomplished due to significant technological and logistical hurdles. Moreover, the effects of spaceflight on microbial pathogenicity and associated infectious disease risks have not been studied. The bacterial pathogen Salmonella typhimurium was grown aboard Space Shuttle mission STS-115 and compared to identical ground control cultures. Global microarray and proteomic analyses revealed 167 transcripts and 73 proteins changed expression with the conserved RNA-binding protein Hfq identified as a likely global regulator involved in the response to this environment. Hfq involvement was confirmed with a ground based microgravity culture model. Spaceflight samples exhibited enhanced virulence in a murine infection model and extracellular matrix accumulation consistent with a biofilm. Strategies to target Hfq and related regulators could potentially decrease infectious disease risks during spaceflight missions and provide novel therapeutic options on Earth.

  17. Calcium Imaging Reveals Coordinated Simple Spike Pauses in Populations of Cerebellar Purkinje Cells

    Directory of Open Access Journals (Sweden)

    Jorge E. Ramirez

    2016-12-01

    Full Text Available The brain’s control of movement is thought to involve coordinated activity between cerebellar Purkinje cells. The results reported here demonstrate that somatic Ca2+ imaging is a faithful reporter of Na+-dependent “simple spike” pauses and enables us to optically record changes in firing rates in populations of Purkinje cells in brain slices and in vivo. This simultaneous calcium imaging of populations of Purkinje cells reveals a striking spatial organization of pauses in Purkinje cell activity between neighboring cells. The source of this organization is shown to be the presynaptic gamma-Aminobutyric acid producing (GABAergic network, and blocking ionotropic gamma-Aminobutyric acid receptor (GABAARs abolishes the synchrony. These data suggest that presynaptic interneurons synchronize (inactivity between neighboring Purkinje cells, and thereby maximize their effect on downstream targets in the deep cerebellar nuclei.

  18. Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans.

    Science.gov (United States)

    Cenik, Can; Cenik, Elif Sarinay; Byeon, Gun W; Grubert, Fabian; Candille, Sophie I; Spacek, Damek; Alsallakh, Bilal; Tilgner, Hagen; Araya, Carlos L; Tang, Hua; Ricci, Emiliano; Snyder, Michael P

    2015-11-01

    Elucidating the consequences of genetic differences between humans is essential for understanding phenotypic diversity and personalized medicine. Although variation in RNA levels, transcription factor binding, and chromatin have been explored, little is known about global variation in translation and its genetic determinants. We used ribosome profiling, RNA sequencing, and mass spectrometry to perform an integrated analysis in lymphoblastoid cell lines from a diverse group of individuals. We find significant differences in RNA, translation, and protein levels suggesting diverse mechanisms of personalized gene expression control. Combined analysis of RNA expression and ribosome occupancy improves the identification of individual protein level differences. Finally, we identify genetic differences that specifically modulate ribosome occupancy--many of these differences lie close to start codons and upstream ORFs. Our results reveal a new level of gene expression variation among humans and indicate that genetic variants can cause changes in protein levels through effects on translation. © 2015 Cenik et al.; Published by Cold Spring Harbor Laboratory Press.

  19. The rumen microbial metaproteome as revealed by SDS-PAGE.

    Science.gov (United States)

    Snelling, Timothy J; Wallace, R John

    2017-01-07

    Ruminal digestion is carried out by large numbers of bacteria, archaea, protozoa and fungi. Understanding the microbiota is important because ruminal fermentation dictates the efficiency of feed utilisation by the animal and is also responsible for major emissions of the greenhouse gas, methane. Recent metagenomic and metatranscriptomic studies have helped to elucidate many features of the composition and activity of the microbiota. The metaproteome provides complementary information to these other -omics technologies. The aim of this study was to explore the metaproteome of bovine and ovine ruminal digesta using 2D SDS-PAGE. Digesta samples were taken via ruminal fistulae and by gastric intubation, or at slaughter, and stored in glycerol at -80 °C. A protein extraction protocol was developed to maximise yield and representativeness of the protein content. The proteome of ruminal digesta taken from dairy cows fed a high concentrate diet was dominated by a few very highly expressed proteins, which were identified by LC-MS/MS to be structural proteins, such as actin and α- and β-tubulins, derived from ciliate protozoa. Removal of protozoa from digesta before extraction of proteins revealed the prokaryotic metaproteome, which was dominated by enzymes involved in glycolysis, such as glyceraldehyde-3-phosphate dehydrogenase, phosphoenolpyruvate carboxykinase, phosphoglycerate kinase and triosephosphate isomerase. The enzymes were predominantly from the Firmicutes and Bacteroidetes phyla. Enzymes from methanogenic archaea were also abundant, consistent with the importance of methane formation in the rumen. Gels from samples from dairy cows fed a high proportion of grass silage were consistently obscured by co-staining of humic compounds. Samples from beef cattle and fattening lambs receiving a predominantly concentrate diet produced clearer gels, but the pattern of spots was inconsistent between samples, making comparisons difficult. This work demonstrated for the

  20. Episodic sexual transmission of HIV revealed by molecular phylodynamics.

    Directory of Open Access Journals (Sweden)

    Fraser Lewis

    2008-03-01

    Full Text Available The structure of sexual contact networks plays a key role in the epidemiology of sexually transmitted infections, and their reconstruction from interview data has provided valuable insights into the spread of infection. For HIV, the long period of infectivity has made the interpretation of contact networks more difficult, and major discrepancies have been observed between the contact network and the transmission network revealed by viral phylogenetics. The high rate of HIV evolution in principle allows for detailed reconstruction of links between virus from different individuals, but often sampling has been too sparse to describe the structure of the transmission network. The aim of this study was to analyze a high-density sample of an HIV-infected population using recently developed techniques in phylogenetics to infer the short-term dynamics of the epidemic among men who have sex with men (MSM.Sequences of the protease and reverse transcriptase coding regions from 2,126 patients, predominantly MSM, from London were compared: 402 of these showed a close match to at least one other subtype B sequence. Nine large clusters were identified on the basis of genetic distance; all were confirmed by Bayesian Monte Carlo Markov chain (MCMC phylogenetic analysis. Overall, 25% of individuals with a close match with one sequence are linked to 10 or more others. Dated phylogenies of the clusters using a relaxed clock indicated that 65% of the transmissions within clusters took place between 1995 and 2000, and 25% occurred within 6 mo after infection. The likelihood that not all members of the clusters have been identified renders the latter observation conservative.Reconstruction of the HIV transmission network using a dated phylogeny approach has revealed the HIV epidemic among MSM in London to have been episodic, with evidence of multiple clusters of transmissions dating to the late 1990s, a period when HIV prevalence is known to have doubled in this