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Sample records for d4 activates distinct

  1. Leukotriene D4 activates distinct G-proteins in intestinal epithelial cells to regulate stress fibre formation and to generate intracellular Ca2+ mobilisation and ERK1/2 activation

    International Nuclear Information System (INIS)

    Nielsen, Christian Kamp; Massoumi, Ramin; Sonnerlind, Maria; Sjoelander, Anita

    2005-01-01

    We have shown that the pro-inflammatory mediator LTD 4 , via its G-protein-coupled receptor CysLT 1 , signals through both pertussis-toxin-sensitive and -insensitive G-proteins to induce various cellular responses. To further characterise the initial step of the different signalling pathways emanating from the CysLT 1 receptor, we transfected intestinal epithelial cells, Int 407, with different mini vectors that each express a specific inhibitory peptide directed against a unique α subunit of a specific heterotrimeric G-protein. Our results revealed that LTD 4 -induced stress fibre formation is inhibited approximately 80% by a vector expressing an inhibitory peptide against the pertussis-toxin-insensitive Gα 12 -protein in intestinal epithelial Int 407 cells. Control experiments revealed that the LPA-induced stress fibre formation, mediated via the Gα 12 -protein in other cell types, was blocked by the same peptide in intestinal Int 407 cells. Furthermore, the CysLT 1 -receptor-mediated calcium signal and activation of the proliferative ERK1/2 kinase are blocked in cells transfected with a vector expressing an inhibitory peptide against the Gα i3 -protein, whereas in cells transfected with an empty ECFP-vector or vectors expressing inhibitory peptides against the Gα i1-2 -, Gα 12 -, Gα R -proteins these signals are not significantly affected. Consequently, the CysLT 1 receptor has the capacity to activate at least two distinctly different heterotrimeric G-proteins that transduce activation of unique downstream cellular events

  2. Conditioned place preference and locomotor activity in response to methylphenidate, amphetamine and cocaine in mice lacking dopamine D4 receptors

    Energy Technology Data Exchange (ETDEWEB)

    Thanos, P.K.; Thanos, P.K.; Bermeo, C.; Rubinstein, M.; Suchland, K.L.; Wang, G.-J.; Grandy, D.K.; Volkow, N.D.

    2010-05-01

    Methylphenidate (MP) and amphetamine (AMPH) are the most frequently prescribed medications for the treatment of attention-deficit/hyperactivity disorder (ADHD). Both drugs are believed to derive their therapeutic benefit by virtue of their dopamine (DA)-enhancing effects, yet an explanation for the observation that some patients with ADHD respond well to one medication but not to the other remains elusive. The dopaminergic effects of MP and AMPH are also thought to underlie their reinforcing properties and ultimately their abuse. Polymorphisms in the human gene that codes for the DA D4 receptor (D4R) have been repeatedly associated with ADHD and may correlate with the therapeutic as well as the reinforcing effects of responses to these psychostimulant medications. Conditioned place preference (CPP) for MP, AMPH and cocaine were evaluated in wild-type (WT) mice and their genetically engineered littermates, congenic on the C57Bl/6J background, that completely lack D4Rs (knockout or KO). In addition, the locomotor activity in these mice during the conditioning phase of CPP was tested in the CPP chambers. D4 receptor KO and WT mice showed CPP and increased locomotor activity in response to each of the three psychostimulants tested. D4R differentially modulates the CPP responses to MP, AMPH and cocaine. While the D4R genotype affected CPP responses to MP (high dose only) and AMPH (low dose only) it had no effects on cocaine. Inasmuch as CPP is considered an indicator of sensitivity to reinforcing responses to drugs these data suggest a significant but limited role of D4Rs in modulating conditioning responses to MP and AMPH. In the locomotor test, D4 receptor KO mice displayed attenuated increases in AMPH-induced locomotor activity whereas responses to cocaine and MP did not differ. These results suggest distinct mechanisms for D4 receptor modulation of the reinforcing (perhaps via attenuating dopaminergic signalling) and locomotor properties of these stimulant drugs

  3. Acute exercise and physiological insulin induce distinct phosphorylation signatures on TBC1D1 and TBC1D4 proteins in human skeletal muscle.

    Science.gov (United States)

    Treebak, Jonas T; Pehmøller, Christian; Kristensen, Jonas M; Kjøbsted, Rasmus; Birk, Jesper B; Schjerling, Peter; Richter, Erik A; Goodyear, Laurie J; Wojtaszewski, Jørgen F P

    2014-01-15

    We investigated the phosphorylation signatures of two Rab-GTPase activating proteins TBC1D1 and TBC1D4 in human skeletal muscle in response to physical exercise and physiological insulin levels induced by a carbohydrate rich meal using a paired experimental design. Eight healthy male volunteers exercised in the fasted or fed state and muscle biopsies were taken before and immediately after exercise. We identified TBC1D1/4 phospho-sites that (1) did not respond to exercise or postprandial increase in insulin (TBC1D4: S666), (2) responded to insulin only (TBC1D4: S318), (3) responded to exercise only (TBC1D1: S237, S660, S700; TBC1D4: S588, S751), and (4) responded to both insulin and exercise (TBC1D1: T596; TBC1D4: S341, T642, S704). In the insulin-stimulated leg, Akt phosphorylation of both T308 and S473 correlated significantly with multiple sites on both TBC1D1 (T596) and TBC1D4 (S318, S341, S704). Interestingly, in the exercised leg in the fasted state TBC1D1 phosphorylation (S237, T596) correlated significantly with the activity of the α2/β2/γ3 AMPK trimer, whereas TBC1D4 phosphorylation (S341, S704) correlated with the activity of the α2/β2/γ1 AMPK trimer. Our data show differential phosphorylation of TBC1D1 and TBC1D4 in response to physiological stimuli in human skeletal muscle and support the idea that Akt and AMPK are upstream kinases. TBC1D1 phosphorylation signatures were comparable between in vitro contracted mouse skeletal muscle and exercised human muscle, and we show that AMPK regulated phosphorylation of these sites in mouse muscle. Contraction and exercise elicited a different phosphorylation pattern of TBC1D4 in mouse compared with human muscle, and although different circumstances in our experimental setup may contribute to this difference, the observation exemplifies that transferring findings between species is problematic.

  4. Acute exercise and physiological insulin induce distinct phosphorylation signatures on TBC1D1 and TBC1D4 in human skeletal muscle

    DEFF Research Database (Denmark)

    Treebak, Jonas Thue; Pehmøller, Christian; Kristensen, Jonas Møller

    2014-01-01

    We investigated the phosphorylation signatures of two Rab GTPase activating proteins TBC1D1 and TBC1D4 in human skeletal muscle in response to physical exercise and physiological insulin levels induced by a carbohydrate rich meal using a paired experimental design. Eight healthy male volunteers e...

  5. Summary report for ITER Task -- D4: Activation calculations for the stainless steel ITER design

    International Nuclear Information System (INIS)

    Attaya, H.

    1995-02-01

    Detailed activation analysis for ITER has been performed as a part of ITER Task D4. The calculations have been performed for the shielding blanket (SS/water) and for the breeding blanket (LiN) options. The activation code RACC-P, which has been modified under IFER Task-D-10 for pulsed operation, has been used in this analysis. The spatial distributions of the radioactive inventory, decay heat, biological hazard potential, and the contact dose were calculated for the two designs for different operation modes and targeted fluences. A one-dimensional toroidal geometrical model has been utilized to determine the neutron fluxes in the two designs. The results are normalized for an inboard and outboard neutron wall loadings of 0.91 and 1.2 MW/M 2 , respectively. The point-wise distributions of the decay gamma sources have been calculated everywhere in the reactor at several times after the shutdown of the two designs and are then used in the transport code ONEDANT to calculate the biological dose everywhere in the reactor. The point-wise distributions of all the responses have also been calculated. These calculations have been performed for neutron fluences of 3.0 MWa/M 2 , which corresponds to the target fluence of ITER, and 0.1 MWa/M 2 , which is anticipated to correspond to the beginning of an extended maintenance period

  6. Dopamine D4 receptor activation increases hippocampal gamma oscillations by enhancing synchronization of fast-spiking interneurons.

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    Richard Andersson

    Full Text Available BACKGROUND: Gamma oscillations are electric activity patterns of the mammalian brain hypothesized to serve attention, sensory perception, working memory and memory encoding. They are disrupted or altered in schizophrenic patients with associated cognitive deficits, which persist in spite of treatment with antipsychotics. Because cognitive symptoms are a core feature of schizophrenia it is relevant to explore signaling pathways that potentially regulate gamma oscillations. Dopamine has been reported to decrease gamma oscillation power via D1-like receptors. Based on the expression pattern of D4 receptors (D4R in hippocampus, and pharmacological effects of D4R ligands in animals, we hypothesize that they are in a position to regulate gamma oscillations as well. METHODOLOGY/PRINCIPAL FINDINGS: To address this hypothesis we use rat hippocampal slices and kainate-induced gamma oscillations. Local field potential recordings as well as intracellular recordings of pyramidal cells, fast-spiking and non-fast-spiking interneurons were carried out. We show that D4R activation with the selective ligand PD168077 increases gamma oscillation power, which can be blocked by the D4R-specific antagonist L745,870 as well as by the antipsychotic drug Clozapine. Pyramidal cells did not exhibit changes in excitatory or inhibitory synaptic current amplitudes, but inhibitory currents became more coherent with the oscillations after application of PD168077. Fast-spiking, but not non-fast spiking, interneurons, increase their action potential phase-coupling and coherence with regard to ongoing gamma oscillations in response to D4R activation. Among several possible mechanisms we found that the NMDA receptor antagonist AP5 also blocks the D4R mediated increase in gamma oscillation power. CONCLUSIONS/SIGNIFICANCE: We conclude that D4R activation affects fast-spiking interneuron synchronization and thereby increases gamma power by an NMDA receptor-dependent mechanism. This

  7. Dopamine D4 receptors modulate brain metabolic activity in the prefrontal cortex and cerebellum at rest and in response to methylphenidate

    Energy Technology Data Exchange (ETDEWEB)

    Michaelides, M.; Wang, G.; Michaelides, M.; Pascau, J.; Gispert, J.-D.; Delis, F.; Grandy, D.K.; Wang, G.-J.; Desco, M.; Rubinstein, M.; Volkow, N.D.; Thanos, P.K.

    2010-07-16

    Methylphenidate (MP) is widely used to treat attention deficit hyperactivity disorder (ADHD). Variable number of tandem repeats polymorphisms in the dopamine D4 receptor (D{sub 4}) gene have been implicated in vulnerability to ADHD and the response to MP. Here we examined the contribution of dopamine D4 receptors (D4Rs) to baseline brain glucose metabolism and to the regional metabolic responses to MP. We compared brain glucose metabolism (measured with micro-positron emission tomography and [{sup 18}F]2-fluoro-2-deoxy-D-glucose) at baseline and after MP (10 mg/kg, i.p.) administration in mice with genetic deletion of the D{sub 4}. Images were analyzed using a novel automated image registration procedure. Baseline D{sub 4}{sup -/-} mice had lower metabolism in the prefrontal cortex (PFC) and greater metabolism in the cerebellar vermis (CBV) than D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice; when given MP, D{sub 4}{sup -/-} mice increased metabolism in the PFC and decreased it in the CBV, whereas in D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice, MP decreased metabolism in the PFC and increased it in the CBV. These findings provide evidence that D4Rs modulate not only the PFC, which may reflect the activation by dopamine of D4Rs located in this region, but also the CBV, which may reflect an indirect modulation as D4Rs are minimally expressed in this region. As individuals with ADHD show structural and/or functional abnormalities in these brain regions, the association of ADHD with D4Rs may reflect its modulation of these brain regions. The differential response to MP as a function of genotype could explain differences in brain functional responses to MP between patients with ADHD and healthy controls and between patients with ADHD with different D{sub 4} polymorphisms.

  8. Identification of a novel phosphorylation site on TBC1D4 regulated by AMP-activated protein kinase in skeletal muscle

    DEFF Research Database (Denmark)

    Treebak, Jonas Thue; Taylor, Eric B.; Witczak, Carol A.

    2010-01-01

    TBC1D4 (also known as AS160) regulates GLUT4 translocation and glucose uptake in adipocytes and skeletal muscle. Its mode of action involves phosphorylation of Serine (S)/Threonine (T) residues by upstream kinases resulting in inactivation of Rab-GAP activity leading to GLUT4 mobilization...

  9. Inhibition of Dengue Virus Replication by a Class of Small-Molecule Compounds That Antagonize Dopamine Receptor D4 and Downstream Mitogen-Activated Protein Kinase Signaling

    Science.gov (United States)

    Smith, Jessica L.; Stein, David A.; Shum, David; Fischer, Matthew A.; Radu, Constantin; Bhinder, Bhavneet; Djaballah, Hakim; Nelson, Jay A.; Früh, Klaus

    2014-01-01

    ABSTRACT Dengue viruses (DENV) are endemic pathogens of tropical and subtropical regions that cause significant morbidity and mortality worldwide. To date, no vaccines or antiviral therapeutics have been approved for combating DENV-associated disease. In this paper, we describe a class of tricyclic small-molecule compounds—dihydrodibenzothiepines (DHBTs), identified through high-throughput screening—with potent inhibitory activity against DENV serotype 2. SKI-417616, a highly active representative of this class, displayed activity against all four serotypes of DENV, as well as against a related flavivirus, West Nile virus (WNV), and an alphavirus, Sindbis virus (SINV). This compound was characterized to determine its mechanism of antiviral activity. Investigation of the stage of the viral life cycle affected revealed that an early event in the life cycle is inhibited. Due to the structural similarity of the DHBTs to known antagonists of the dopamine and serotonin receptors, we explored the roles of two of these receptors, serotonin receptor 2A (5HTR2A) and the D4 dopamine receptor (DRD4), in DENV infection. Antagonism of DRD4 and subsequent downstream phosphorylation of epidermal growth factor receptor (EGFR)-related kinase (ERK) were found to impact DENV infection negatively, and blockade of signaling through this network was confirmed as the mechanism of anti-DENV activity for this class of compounds. IMPORTANCE The dengue viruses are mosquito-borne, reemerging human pathogens that are the etiological agents of a spectrum of febrile diseases. Currently, there are no approved therapeutic treatments for dengue-associated disease, nor is there a vaccine. This study identifies a small molecule, SKI-417616, with potent anti-dengue virus activity. Further analysis revealed that SKI-417616 acts through antagonism of the host cell dopamine D4 receptor and subsequent repression of the ERK phosphorylation pathway. These results suggest that SKI-417616, or other

  10. Distinct activities of Bartonella henselae type IV secretion effector proteins modulate capillary-like sprout formation.

    Science.gov (United States)

    Scheidegger, F; Ellner, Y; Guye, P; Rhomberg, T A; Weber, H; Augustin, H G; Dehio, C

    2009-07-01

    The zoonotic pathogen Bartonella henselae (Bh) can lead to vasoproliferative tumour lesions in the skin and inner organs known as bacillary angiomatosis and bacillary peliosis. The knowledge on the molecular and cellular mechanisms involved in this pathogen-triggered angiogenic process is confined by the lack of a suitable animal model and a physiologically relevant cell culture model of angiogenesis. Here we employed a three-dimensional in vitro angiogenesis assay of collagen gel-embedded endothelial cell (EC) spheroids to study the angiogenic properties of Bh. Spheroids generated from Bh-infected ECs displayed a high capacity to form sprouts, which represent capillary-like projections into the collagen gel. The VirB/VirD4 type IV secretion system and a subset of its translocated Bartonella effector proteins (Beps) were found to profoundly modulate this Bh-induced sprouting activity. BepA, known to protect ECs from apoptosis, strongly promoted sprout formation. In contrast, BepG, triggering cytoskeletal rearrangements, potently inhibited sprouting. Hence, the here established in vitro model of Bartonella- induced angiogenesis revealed distinct and opposing activities of type IV secretion system effector proteins, which together with a VirB/VirD4-independent effect may control the angiogenic activity of Bh during chronic infection of the vasculature.

  11. Return of D4 Dopamine Receptor Antagonists in Drug Discovery.

    Science.gov (United States)

    Lindsley, Craig W; Hopkins, Corey R

    2017-09-14

    The dopamine D 4 receptor garnered a great deal of interest in the early 1990s when studies showed the atypical antipsychotic clozapine possessed higher affinity for D 4 , relative to other dopamine receptor subtypes, and that this activity might underlie the unique clinical efficacy of clozapine. Unfortunately, D 4 antagonists that were developed for schizophrenia failed in the clinic. Thus, D 4 fell out of favor as a therapeutic target, and work in this area was silent for decades. Recently, D 4 ligands with improved selectivity for D 4 against not only D 1-3,5 but also other biogenic amine targets have emerged, and D 4 is once again in the spotlight as a novel target for both addiction and Parkinson's disease (PD), as well as other emerging diseases. This report will review the historical data for D 4 , review the known D 4 ligands, and then highlight new data supporting a role for D 4 inhibition in addiction, PD, and cancer.

  12. Distinct patterns of brain activity characterise lexical activation and competition in spoken word production.

    Directory of Open Access Journals (Sweden)

    Vitória Piai

    Full Text Available According to a prominent theory of language production, concepts activate multiple associated words in memory, which enter into competition for selection. However, only a few electrophysiological studies have identified brain responses reflecting competition. Here, we report a magnetoencephalography study in which the activation of competing words was manipulated by presenting pictures (e.g., dog with distractor words. The distractor and picture name were semantically related (cat, unrelated (pin, or identical (dog. Related distractors are stronger competitors to the picture name because they receive additional activation from the picture relative to other distractors. Picture naming times were longer with related than unrelated and identical distractors. Phase-locked and non-phase-locked activity were distinct but temporally related. Phase-locked activity in left temporal cortex, peaking at 400 ms, was larger on unrelated than related and identical trials, suggesting differential activation of alternative words by the picture-word stimuli. Non-phase-locked activity between roughly 350-650 ms (4-10 Hz in left superior frontal gyrus was larger on related than unrelated and identical trials, suggesting differential resolution of the competition among the alternatives, as reflected in the naming times. These findings characterise distinct patterns of activity associated with lexical activation and competition, supporting the theory that words are selected by competition.

  13. Leukotriene D4 induces chemotaxis in human eosinophilc cell line, EoL-1 cells via CysLT1 receptor activation.

    Science.gov (United States)

    Shirasaki, Hideaki; Kanaizumi, Etsuko; Himi, Tetsuo

    2017-11-01

    Numerous reports have shown that cysteinyl leukotrienes (CysLTs) contribute to tissue accumulation of eosinophils in allergic airway inflammation. To date, only a few studies have reported that CysLTs promote chemotactic activity of human eosinophils in vitro. The purpose of this study was to investigate whether CysLTs promote chemotaxis in the human eosinophilic cell line, EoL-1. EoL-1 cells were induced to differentiate into mature eosinophil-like cells via incubation with butyric acid and cytokines (IL-3, IL-5 and GM-CSF). The chemotactic activity of the differentiated EoL-1 cells was assessed using the commercial cell migration assay kit. LTD 4 elicited dose-related chemotactic activity in the differntiated EoL-1 cells in the range of 1-100 nM. A typical bell-shaped dose-response curve was observed with optimal activity at 10 nM. The chemotactic activity elicited by LTD 4 (10 nM) was significantly inhibited by montelukast (control, 345 ± 19.2 × 10 3 RFU; LTD 4 10 nM alone, 511 ± 39.2 × 10 3 RFU; LTD 4 10 nM plus montelukast 100 nM, 387 ± 28.2 × 10 3 RFU). LTD 4 induces migration in eosinophilic cells via activation of CysLT1 receptor. The present in vitro model may be useful for elucidation of the mechanism underlying CysLT-induced tissue eosinophilia.

  14. NK cell activation: distinct stimulatory pathways counterbalancing inhibitory signals.

    Science.gov (United States)

    Bakker, A B; Wu, J; Phillips, J H; Lanier, L L

    2000-01-01

    A delicate balance between positive and negative signals regulates NK cell effector function. Activation of NK cells may be initiated by the triggering of multiple adhesion or costimulatory molecules, and can be counterbalanced by inhibitory signals induced by receptors for MHC class I. A common pathway of inhibitory signaling is provided by immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in the cytoplasmic domains of these receptors which mediate the recruitment of SH2 domain-bearing tyrosine phosphate-1 (SHP-1). In contrast to the extensive progress that has been made regarding the negative regulation of NK cell function, our knowledge of the signals that activate NK cells is still poor. Recent studies of the activating receptor complexes have shed new light on the induction of NK cell effector function. Several NK receptors using novel adaptors with immunoreceptor tyrosine-based activation motifs (ITAMs) and with PI 3-kinase recruiting motifs have been implicated in NK cell stimulation.

  15. Different bacteriocin activities of Streptococcus mutans reflect distinct phylogenetic lineages

    DEFF Research Database (Denmark)

    Balakrishnan, M; Simmonds, RS; Kilian, Mogens

    2002-01-01

    Bacteriocins produced by mutans streptococci are known as mutacins. In this study 16 broadly active mutacin-producing Streptococcus mutans strains from New Zealand, North America and Europe were classified into four groups (A-D) on the basis of differences in their activity in deferred antagonism...... described by Caufield and co-workers. One of the New Zealand isolates of group A (S. mutans strain N) appeared to produce inhibitory activity similar to that of the group I prototype strain UA140. Four other New Zealand isolates of group B (S. mutans strains M19, M34, B34 and D14) had mutacin II......-like activity. The group B mutacin producers differed from the group A mutacin producers in their additional activity against Staph. aureus 46. Seven S. mutans strains (M46, B46, B57, M12, M28, B28 and 13M) were distinguished from the group A and group B mutacin producers in that they inhibited E. faecium TE1...

  16. Siloxane D4 capture by hydrophobic microporous materials

    OpenAIRE

    Mito-oka, Yasuko; Horike, Satoshi; Nishitani, Yusuke; Masumori, Tadao; Inukai, Munehiro; Hijikata, Yuh; Kitagawa, Susumu

    2013-01-01

    Porous substances, including crystalline coordination materials and an amorphous organic polymer, were studied for their selective adsorption of siloxane D4. The investigated materials demonstrated a level of uptake comparable to that of conventional activated carbon.

  17. Localizing Brain Activity from Multiple Distinct Sources via EEG

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    George Dassios

    2014-01-01

    Full Text Available An important question arousing in the framework of electroencephalography (EEG is the possibility to recognize, by means of a recorded surface potential, the number of activated areas in the brain. In the present paper, employing a homogeneous spherical conductor serving as an approximation of the brain, we provide a criterion which determines whether the measured surface potential is evoked by a single or multiple localized neuronal excitations. We show that the uniqueness of the inverse problem for a single dipole is closely connected with attaining certain relations connecting the measured data. Further, we present the necessary and sufficient conditions which decide whether the collected data originates from a single dipole or from numerous dipoles. In the case where the EEG data arouses from multiple parallel dipoles, an isolation of the source is, in general, not possible.

  18. Distinct mechanisms regulate Lck spatial organization in activated T cells

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    Natasha eKapoor-Kaushik

    2016-03-01

    Full Text Available Phosphorylation of the T cell receptor (TCR by the kinase Lck is the first detectable signaling event upon antigen engagement. The distribution of Lck within the plasma membrane, its conformational state, kinase activity and protein interactions all contribute to determine how efficiently Lck phosphorylates the engaged TCR. Here we used cross-correlation raster image spectroscopy (ccRICS and photoactivated localization microscopy (PALM to identify two mechanisms of Lck clustering: an intrinsic mechanism of Lck clustering induced by locking Lck in its open conformation, and an extrinsic mechanism of clustering controlled by the phosphorylation of tyrosine 192, which regulates the affinity of Lck SH2 domain. Both mechanisms of clustering were differently affected by the absence of the kinase Zap70 or the adaptor Lat. We further observed that the adaptor TSAd bound to and promoted the diffusion of Lck when it is phosphorylated on tyrosine 192. Our data suggest that while Lck open conformation drives aggregation and clustering, the spatial organization of Lck is further controlled by signaling events downstream of TCR phosphorylation.

  19. Development of Distinction Method of Production Area of Ginsengs by Using a Neutron Activation Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Jin; Chung, Yong Sam; Sun, Gwang Min; Lee, Yu Na; Yoo, Sang Ho [KAERI, Daejeon (Korea, Republic of)

    2010-05-15

    Distinction of production area of Korean ginsengs has been tried by using neutron activation techniques such as an instrumental neutron activation analysis (INAA) and a prompt gamma activation analysis (PGAA). A distribution of elements has varied according to the part of plant clue to the difference of enrichment effect and influence from a soil where the plants have been grown. So correlation study between plants and soil has been an Issue. In this study, the distribution of trace elements within a Korean ginseng was investigated by using an instrumental neutron activation analysis

  20. The vanishing volume of D = 4 superspace

    Energy Technology Data Exchange (ETDEWEB)

    Bossard, Guillaume, E-mail: bossard@cpht.polytechnique.f [Ecole Polytechnique (CNRS), Palaiseau Cedex (France). Centre de Physique Theorique; Howe, P.S., E-mail: paul.howe@kcl.ac.u [University of London (United Kingdom). King' s College. Dept. of Mathematics; Stelle, K.S., E-mail: stelle@imperial.ac.u [Imperial College London (United Kingdom). Theoretical Physics Group; Vanhove, Pierre, E-mail: pierre.vanhove@cea.f [University of California, Santa Barbara, CA (United States). Kavli Inst. for Theoretical Physics

    2011-07-01

    The volume of on-shell D = 4, N = 8 superspace is shown to vanish. Despite this, it is shown that there is a fully supersymmetric and duality-invariant candidate {nabla}{sup 8}R{sup 4} counterterm corresponding to an anticipated seven-loop logarithmic divergence in D = 4. We construct this counterterm explicitly and also give the complete nonlinear extension of the 1=8-BPS {nabla}{sup 6}R{sup 4} invariant. Similar results are derived for N = 4; 5 and 6. (author)

  1. Task-dependent activation of distinct fast and slow(er) motor pathways during motor imagery.

    Science.gov (United States)

    Keller, Martin; Taube, Wolfgang; Lauber, Benedikt

    2018-02-22

    Motor imagery and actual movements share overlapping activation of brain areas but little is known about task-specific activation of distinct motor pathways during mental simulation of movements. For real contractions, it was demonstrated that the slow(er) motor pathways are activated differently in ballistic compared to tonic contractions but it is unknown if this also holds true for imagined contractions. The aim of the present study was to assess the activity of fast and slow(er) motor pathways during mentally simulated movements of ballistic and tonic contractions. H-reflexes were conditioned with transcranial magnetic stimulation at different interstimulus intervals to assess the excitability of fast and slow(er) motor pathways during a) the execution of tonic and ballistic contractions, b) motor imagery of these contraction types, and c) at rest. In contrast to the fast motor pathways, the slow(er) pathways displayed a task-specific activation: for imagined ballistic as well as real ballistic contractions, the activation was reduced compared to rest whereas enhanced activation was found for imagined tonic and real tonic contractions. This study provides evidence that the excitability of fast and slow(er) motor pathways during motor imagery resembles the activation pattern observed during real contractions. The findings indicate that motor imagery results in task- and pathway-specific subliminal activation of distinct subsets of neurons in the primary motor cortex. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  2. Metacridamide B methanol-d4 monosolvate

    Science.gov (United States)

    The title compound was extracted from conidia of the fungus Metarhizium acridum. Crystals were obtained as a methanol-d4 solvate. The tail part of the 4-methylhexan-2-yl group exhibits disorder over two positions, with an occupancy ratio of 0.682 (9):0.318 (9). The crystal structure confirms the abs...

  3. Active zone proteins are transported via distinct mechanisms regulated by Par-1 kinase.

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    Kara R Barber

    2017-02-01

    Full Text Available Disruption of synapses underlies a plethora of neurodevelopmental and neurodegenerative disease. Presynaptic specialization called the active zone plays a critical role in the communication with postsynaptic neuron. While the role of many proteins at the active zones in synaptic communication is relatively well studied, very little is known about how these proteins are transported to the synapses. For example, are there distinct mechanisms for the transport of active zone components or are they all transported in the same transport vesicle? Is active zone protein transport regulated? In this report we show that overexpression of Par-1/MARK kinase, a protein whose misregulation has been implicated in Autism spectrum disorders (ASDs and neurodegenerative disorders, lead to a specific block in the transport of an active zone protein component- Bruchpilot at Drosophila neuromuscular junctions. Consistent with a block in axonal transport, we find a decrease in number of active zones and reduced neurotransmission in flies overexpressing Par-1 kinase. Interestingly, we find that Par-1 acts independently of Tau-one of the most well studied substrates of Par-1, revealing a presynaptic function for Par-1 that is independent of Tau. Thus, our study strongly suggests that there are distinct mechanisms that transport components of active zones and that they are tightly regulated.

  4. Phenotype specific analyses reveal distinct regulatory mechanism for chronically activated p53.

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    Kristina Kirschner

    2015-03-01

    Full Text Available The downstream functions of the DNA binding tumor suppressor p53 vary depending on the cellular context, and persistent p53 activation has recently been implicated in tumor suppression and senescence. However, genome-wide information about p53-target gene regulation has been derived mostly from acute genotoxic conditions. Using ChIP-seq and expression data, we have found distinct p53 binding profiles between acutely activated (through DNA damage and chronically activated (in senescent or pro-apoptotic conditions p53. Compared to the classical 'acute' p53 binding profile, 'chronic' p53 peaks were closely associated with CpG-islands. Furthermore, the chronic CpG-island binding of p53 conferred distinct expression patterns between senescent and pro-apoptotic conditions. Using the p53 targets seen in the chronic conditions together with external high-throughput datasets, we have built p53 networks that revealed extensive self-regulatory 'p53 hubs' where p53 and many p53 targets can physically interact with each other. Integrating these results with public clinical datasets identified the cancer-associated lipogenic enzyme, SCD, which we found to be directly repressed by p53 through the CpG-island promoter, providing a mechanistic link between p53 and the 'lipogenic phenotype', a hallmark of cancer. Our data reveal distinct phenotype associations of chronic p53 targets that underlie specific gene regulatory mechanisms.

  5. New gauged N = 8, D = 4 supergravities

    International Nuclear Information System (INIS)

    Hull, C M

    2003-01-01

    New gaugings of four-dimensional N = 8 supergravity are constructed, including one which has a Minkowski space vacuum that preserves N = 2 supersymmetry and in which the gauge group is broken to SU(3) x U(1) 2 . Previous gaugings used the form of the ungauged action which is invariant under a rigid SL (8,R) symmetry and promoted a 28-dimensional subgroup (SO(8), SO(p, 8 - p) or the non-semi-simple contraction CSO(p, q, 8 - p - q)) to a local gauge group. Here, a dual form of the ungauged action is used which is invariant under SU*(8) instead of SL (8,R) and new theories are obtained by gauging 28-dimensional subgroups of SU*(8). The gauge groups are non-semi-simple and are different real forms of the CSO(2p, 8 - 2p) groups, denoted as CSO*(2p, 8 - 2p), and the new theories have a rigid SU(2) symmetry. The five-dimensional gauged N = 8 supergravities are dimensionally reduced to D = 4. The D = 5, SO(p, 6 - p) gauge theories reduce, after a duality transformation, to the D = 4, CSO(p, 6 - p, 2) gauging while the SO*(6) gauge theory reduces to the D = 4, CSO*(6, 2) gauge theory. The new theories are related to the old ones via an analytic continuation. The non-semi-simple gaugings can be dualized to forms with different gauge groups

  6. Locomotor activity: A distinctive index in morphine self-administration in rats

    Science.gov (United States)

    Kong, Qingyao

    2017-01-01

    Self-administration of addictive drugs is a widely used tool for studying behavioral, neurobiological, and genetic factors in addiction. However, how locomotor activity is affected during self-administration of addictive drugs has not been extensively studied. In our present study, we tested the locomotor activity levels during acquisition, extinction and reinstatement of morphine self-administration in rats. We found that compared with saline self-administration (SA), rats that trained with morphine SA had higher locomotor activity. Rats that successfully acquired SA also showed higher locomotor activity than rats that failed in acquiring SA. Moreover, locomotor activity was correlated with the number of drug infusions but not with the number of inactive pokes. We also tested the locomotor activity in the extinction and the morphine-primed reinstatement session. Interestingly, we found that in the first extinction session, although the number of active pokes did not change, the locomotor activity was significantly lower than in the last acquisition session, and this decrease can be maintained for at least six days. Finally, morphine priming enhanced the locomotor activity during the reinstatement test, regardless of if the active pokes were significantly increased or not. Our results clearly suggest that locomotor activity, which may reflect the pharmacological effects of morphine, is different from drug seeking behavior and is a distinctive index in drug self-administration. PMID:28380023

  7. Locomotor activity: A distinctive index in morphine self-administration in rats.

    Science.gov (United States)

    Zhang, Jian-Jun; Kong, Qingyao

    2017-01-01

    Self-administration of addictive drugs is a widely used tool for studying behavioral, neurobiological, and genetic factors in addiction. However, how locomotor activity is affected during self-administration of addictive drugs has not been extensively studied. In our present study, we tested the locomotor activity levels during acquisition, extinction and reinstatement of morphine self-administration in rats. We found that compared with saline self-administration (SA), rats that trained with morphine SA had higher locomotor activity. Rats that successfully acquired SA also showed higher locomotor activity than rats that failed in acquiring SA. Moreover, locomotor activity was correlated with the number of drug infusions but not with the number of inactive pokes. We also tested the locomotor activity in the extinction and the morphine-primed reinstatement session. Interestingly, we found that in the first extinction session, although the number of active pokes did not change, the locomotor activity was significantly lower than in the last acquisition session, and this decrease can be maintained for at least six days. Finally, morphine priming enhanced the locomotor activity during the reinstatement test, regardless of if the active pokes were significantly increased or not. Our results clearly suggest that locomotor activity, which may reflect the pharmacological effects of morphine, is different from drug seeking behavior and is a distinctive index in drug self-administration.

  8. Development of distinction method of production area of ginsengs by using a neutron activation analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Youngjin; Chung, Yongsam; Sim, Chulmuu; Sun, Gwangmin; Lee, Yuna; Yoo, Sangho

    2011-01-15

    During the last 2 years of the project, we have tried to develop the technology to make a distinction of the production areas for Korean ginsengs cultivated in the various provinces in Korea and foreign countries. It will contribute to secure the health food safety for public and stability of its market. In this year, we collected ginseng samples cultivated in the northeastern province in Chinese mainland such as Liaoning province, Jilin province and Baekdu mountain within Jilin province. 10 ginseng samples were collected at each province. The elemental concentrations in the ginseng were analyzed by using a neutron activation analysis technique at the HANARO research reactor. The distinction of production area was made by using a statistical software. As a result, the Chinese Korean ginsengs were certainly differentiated from those cultivated in the famous province in Korea though there was a limitation that the number of our sample we analyzed is very small.

  9. Development of distinction method of production area of ginsengs by using a neutron activation analysis

    International Nuclear Information System (INIS)

    Kim, Youngjin; Chung, Yongsam; Sim, Chulmuu; Sun, Gwangmin; Lee, Yuna; Yoo, Sangho

    2011-01-01

    During the last 2 years of the project, we have tried to develop the technology to make a distinction of the production areas for Korean ginsengs cultivated in the various provinces in Korea and foreign countries. It will contribute to secure the health food safety for public and stability of its market. In this year, we collected ginseng samples cultivated in the northeastern province in Chinese mainland such as Liaoning province, Jilin province and Baekdu mountain within Jilin province. 10 ginseng samples were collected at each province. The elemental concentrations in the ginseng were analyzed by using a neutron activation analysis technique at the HANARO research reactor. The distinction of production area was made by using a statistical software. As a result, the Chinese Korean ginsengs were certainly differentiated from those cultivated in the famous province in Korea though there was a limitation that the number of our sample we analyzed is very small

  10. PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance.

    Science.gov (United States)

    van Oers, Johanna M M; Roa, Sergio; Werling, Uwe; Liu, Yiyong; Genschel, Jochen; Hou, Harry; Sellers, Rani S; Modrich, Paul; Scharff, Matthew D; Edelmann, Winfried

    2010-07-27

    The DNA mismatch repair protein PMS2 was recently found to encode a novel endonuclease activity. To determine the biological functions of this activity in mammals, we generated endonuclease-deficient Pms2E702K knock-in mice. Pms2EK/EK mice displayed increased genomic mutation rates and a strong cancer predisposition. In addition, class switch recombination, but not somatic hypermutation, was impaired in Pms2EK/EK B cells, indicating a specific role in Ig diversity. In contrast to Pms2-/- mice, Pms2EK/EK male mice were fertile, indicating that this activity is dispensable in spermatogenesis. Therefore, the PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance and tumor suppression.

  11. Rac1 GTPase activates the WAVE regulatory complex through two distinct binding sites

    Science.gov (United States)

    Brautigam, Chad A; Xing, Wenmin; Yang, Sheng; Henry, Lisa; Doolittle, Lynda K; Walz, Thomas

    2017-01-01

    The Rho GTPase Rac1 activates the WAVE regulatory complex (WRC) to drive Arp2/3 complex-mediated actin polymerization, which underpins diverse cellular processes. Here we report the structure of a WRC-Rac1 complex determined by cryo-electron microscopy. Surprisingly, Rac1 is not located at the binding site on the Sra1 subunit of the WRC previously identified by mutagenesis and biochemical data. Rather, it binds to a distinct, conserved site on the opposite end of Sra1. Biophysical and biochemical data on WRC mutants confirm that Rac1 binds to both sites, with the newly identified site having higher affinity and both sites required for WRC activation. Our data reveal that the WRC is activated by simultaneous engagement of two Rac1 molecules, suggesting a mechanism by which cells may sense the density of active Rac1 at membranes to precisely control actin assembly. PMID:28949297

  12. Welfare effects of deterrence-motivated activation policy: the case of distinct activation-disutility

    DEFF Research Database (Denmark)

    Rasmussen, Martin

    We investigate conditions for activation policy to be part of an optimal policy, when the motivation for activation is to deter people from collecting benefits. A benevolent government chooses a pure benefit programme and an activation programme and individuals self-select into programmes or work...

  13. Distinct developmental defense activations in barley embryos identified by transcriptome profiling

    DEFF Research Database (Denmark)

    Nielsen, ME; Lok, F; Nielsen, Henrik Bjørn

    2006-01-01

    analyses of > 22,000 genes, which together with measurements of jasmonic acid and salicylic acid during embryo development provide new information on the initiation in the developing barley embryo of at least two distinct types of developmental defense activation (DDA). Early DDA is characterized by the up......-regulation of several PR genes is notable. Throughout barley embryo development, there are no indications of an increased biosynthesis of either jasmonic acid or salicylic acid. Collectively, the results help explain how the proposed DDA enables protection of the developing barley embryo and grain for purposes...

  14. Supersymmetrization schemes of D=4 Maxwell algebra

    International Nuclear Information System (INIS)

    Kamimura, Kiyoshi; Lukierski, Jerzy

    2012-01-01

    The Maxwell algebra, an enlargement of Poincaré algebra by Abelian tensorial generators, can be obtained in arbitrary dimension D by the suitable contraction of O(D-1,1)⊕O(D-1,2) (Lorentz algebra ⊕ AdS algebra). We recall that in D=4 the Lorentz algebra O(3,1) is described by the realification Sp R (2|C) of complex algebra Sp(2|C)≃Sl(2|C) and O(3,2)≃Sp(4). We study various D=4N-extended Maxwell superalgebras obtained by the contractions of real superalgebras OSp R (2N-k;2|C)⊕OSp(k;4) (k=0,1,2,…,2N); (extended Lorentz superalgebra ⊕ extended AdS superalgebra). If N=1 (k=0,1,2) one arrives at three different versions of simple Maxwell superalgebra. For any fixed N we get 2N different superextensions of Maxwell algebra with n-extended Poincaré superalgebras (1⩽n⩽N) and the internal symmetry sectors obtained by suitable contractions of the real algebra O R (2N-k|C)⊕O(k). Finally the comments on possible applications of Maxwell superalgebras are presented.

  15. Distinct Patterns of Brain Activity Characterise Lexical Activation and Competition in Spoken Word Production

    NARCIS (Netherlands)

    Piai, V.; Roelofs, A.P.A.; Jensen, O.; Schoffelen, J.M.; Bonnefond, M.

    2014-01-01

    According to a prominent theory of language production, concepts activate multiple associated words in memory, which enter into competition for selection. However, only a few electrophysiological studies have identified brain responses reflecting competition. Here, we report a magnetoencephalography

  16. Correlation of neural activity with behavioral kinematics reveals distinct sensory encoding and evidence accumulation processes during active tactile sensing.

    Science.gov (United States)

    Delis, Ioannis; Dmochowski, Jacek P; Sajda, Paul; Wang, Qi

    2018-03-23

    Many real-world decisions rely on active sensing, a dynamic process for directing our sensors (e.g. eyes or fingers) across a stimulus to maximize information gain. Though ecologically pervasive, limited work has focused on identifying neural correlates of the active sensing process. In tactile perception, we often make decisions about an object/surface by actively exploring its shape/texture. Here we investigate the neural correlates of active tactile decision-making by simultaneously measuring electroencephalography (EEG) and finger kinematics while subjects interrogated a haptic surface to make perceptual judgments. Since sensorimotor behavior underlies decision formation in active sensing tasks, we hypothesized that the neural correlates of decision-related processes would be detectable by relating active sensing to neural activity. Novel brain-behavior correlation analysis revealed that three distinct EEG components, localizing to right-lateralized occipital cortex (LOC), middle frontal gyrus (MFG), and supplementary motor area (SMA), respectively, were coupled with active sensing as their activity significantly correlated with finger kinematics. To probe the functional role of these components, we fit their single-trial-couplings to decision-making performance using a hierarchical-drift-diffusion-model (HDDM), revealing that the LOC modulated the encoding of the tactile stimulus whereas the MFG predicted the rate of information integration towards a choice. Interestingly, the MFG disappeared from components uncovered from control subjects performing active sensing but not required to make perceptual decisions. By uncovering the neural correlates of distinct stimulus encoding and evidence accumulation processes, this study delineated, for the first time, the functional role of cortical areas in active tactile decision-making. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Distinct Neural Activity Associated with Focused-Attention Meditation and Loving-Kindness Meditation

    Science.gov (United States)

    Lee, Tatia M. C.; Leung, Mei-Kei; Hou, Wai-Kai; Tang, Joey C. Y.; Yin, Jing; So, Kwok-Fai; Lee, Chack-Fan; Chan, Chetwyn C. H.

    2012-01-01

    This study examined the dissociable neural effects of ānāpānasati (focused-attention meditation, FAM) and mettā (loving-kindness meditation, LKM) on BOLD signals during cognitive (continuous performance test, CPT) and affective (emotion-processing task, EPT, in which participants viewed affective pictures) processing. Twenty-two male Chinese expert meditators (11 FAM experts, 11 LKM experts) and 22 male Chinese novice meditators (11 FAM novices, 11 LKM novices) had their brain activity monitored by a 3T MRI scanner while performing the cognitive and affective tasks in both meditation and baseline states. We examined the interaction between state (meditation vs. baseline) and expertise (expert vs. novice) separately during LKM and FAM, using a conjunction approach to reveal common regions sensitive to the expert meditative state. Additionally, exclusive masking techniques revealed distinct interactions between state and group during LKM and FAM. Specifically, we demonstrated that the practice of FAM was associated with expertise-related behavioral improvements and neural activation differences in attention task performance. However, the effect of state LKM meditation did not carry over to attention task performance. On the other hand, both FAM and LKM practice appeared to affect the neural responses to affective pictures. For viewing sad faces, the regions activated for FAM practitioners were consistent with attention-related processing; whereas responses of LKM experts to sad pictures were more in line with differentiating emotional contagion from compassion/emotional regulation processes. Our findings provide the first report of distinct neural activity associated with forms of meditation during sustained attention and emotion processing. PMID:22905090

  18. Activity-based anorexia activates nesfatin-1 immunoreactive neurons in distinct brain nuclei of female rats.

    Science.gov (United States)

    Scharner, Sophie; Prinz, Philip; Goebel-Stengel, Miriam; Lommel, Reinhard; Kobelt, Peter; Hofmann, Tobias; Rose, Matthias; Stengel, Andreas

    2017-12-15

    Activity-based anorexia (ABA) is an established animal model for the eating disorder anorexia nervosa (AN). The pathophysiology of AN and the involvement of food intake-regulatory peptides is still poorly understood. Nesfatin-1, an anorexigenic peptide also involved in the mediation of stress, anxiety and depression might be a likely candidate involved in the pathogenesis of AN. Therefore, activation of nesfatin-1 immunoreactive (ir) brain nuclei was investigated under conditions of ABA. Female Sprague-Dawley rats were used and divided into four groups (n=6/group): activity-based anorexia (ABA), restricted feeding (RF), activity (AC) and ad libitum fed (AL). After the 21-day experimental period and development of ABA, brains were processed for c-Fos/nesfatin-1 double labeling immunohistochemistry. ABA increased the number of nesfatin-1 immunopositive neurons in the paraventricular nucleus, arcuate nucleus, dorsomedial hypothalamic nucleus, locus coeruleus and in the rostral part of the nucleus of the solitary tract compared to AL and AC groups (p0.05). Moreover, we observed significantly more c-Fos and nesfatin-1 ir double-labeled cells in ABA rats compared to RF, AL and AC in the supraoptic nucleus (p<0.05) and compared to AL and AC in the paraventricular nucleus, arcuate nucleus, dorsomedial hypothalamic nucleus, dorsal raphe nucleus and the rostral raphe pallidus (p<0.05). Since nesfatin-1 plays a role in the inhibition of food intake and the response to stress, we hypothesize that the observed changes of brain nesfatin-1 might play a role in the pathophysiology and symptomatology under conditions of ABA and potentially also in patients with AN. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Overexpression of cypin alters dendrite morphology, single neuron activity, and network properties via distinct mechanisms

    Science.gov (United States)

    Rodríguez, Ana R.; O'Neill, Kate M.; Swiatkowski, Przemyslaw; Patel, Mihir V.; Firestein, Bonnie L.

    2018-02-01

    Objective. This study investigates the effect that overexpression of cytosolic PSD-95 interactor (cypin), a regulator of synaptic PSD-95 protein localization and a core regulator of dendrite branching, exerts on the electrical activity of rat hippocampal neurons and networks. Approach. We cultured rat hippocampal neurons and used lipid-mediated transfection and lentiviral gene transfer to achieve high levels of cypin or cypin mutant (cypinΔPDZ PSD-95 non-binding) expression cellularly and network-wide, respectively. Main results. Our analysis revealed that although overexpression of cypin and cypinΔPDZ increase dendrite numbers and decrease spine density, cypin and cypinΔPDZ distinctly regulate neuronal activity. At the single cell level, cypin promotes decreases in bursting activity while cypinΔPDZ reduces sEPSC frequency and further decreases bursting compared to cypin. At the network level, by using the Fano factor as a measure of spike count variability, cypin overexpression results in an increase in variability of spike count, and this effect is abolished when cypin cannot bind PSD-95. This variability is also dependent on baseline activity levels and on mean spike rate over time. Finally, our spike sorting data show that overexpression of cypin results in a more complex distribution of spike waveforms and that binding to PSD-95 is essential for this complexity. Significance. Our data suggest that dendrite morphology does not play a major role in cypin action on electrical activity.

  20. Distinct ontogenic patterns of overt and latent DGAT activities of rat liver microsomes.

    Science.gov (United States)

    Waterman, Ian J; Price, Nigel T; Zammit, Victor A

    2002-09-01

    We have studied the ontogeny of the two functional diacylglycerol acyltransferase (DGAT) activities (overt and latent) during postnatal development in rat liver. We find that the ontogenic patterns of the two are highly distinct. Overt DGAT shows a transient rise in activity up to day 4 postnatally, after which it declines until weaning; thereafter, it increases steadily to reach high adult values that may contribute to the high rates of turnover of cytosolic triacylglycerol (TAG). By contrast, latent DGAT activity increases continuously during the suckling period but falls sharply upon weaning onto chow but not onto a high-fat diet. Rates of TAG secretion by hepatocytes are higher than in the adult during the first 7 days after birth, and are largely dependent on the mobilization of the abundant intrahepatocyte TAG as a source of acyl moieties. When the hepatic steatosis is cleared (after day 7) the TAG secretion rate declines by 80% to reach adult values. Quantification of the content of mRNA for the DGAT1 and DGAT2 genes does not show correlation with either of the DGAT activities. We conclude that post-translational modification may play an important role in the overt and latent distribution of DGAT activity in the liver microsomal membrane.

  1. Exercise versus Nonexercise Activity: E-diaries Unravel Distinct Effects on Mood.

    Science.gov (United States)

    Reichert, Markus; Tost, Heike; Reinhard, Iris; Schlotz, Wolff; Zipf, Alexander; Salize, Hans-Joachim; Meyer-Lindenberg, Andreas; Ebner-Priemer, Ulrich W

    2017-04-01

    The association between physical activity and mood is of major importance to increase physical activity as a prevention strategy for noncommunicable diseases and to improve mental health. Unfortunately, existing studies examining how physical activity and mood wax and wane within persons over time in everyday life do show ambiguous findings. Taking a closer look at these studies reveals that the aggregation levels differ tremendously. Whereas mood is conceptualized as a three-dimensional construct, physical activity is treated as a global construct not taking into account its distinct components like exercise (such as jogging) and nonexercise activity (NEA; such as climbing stairs). To overcome these limitations, we conducted an ambulatory assessment study on the everyday life of 106 adults over 7 d continuously measuring NEA via accelerometers and repeatedly querying for mood in real time via GPS-triggered e-diaries. We used multilevel modeling to derive differential within-subject effects of exercise versus NEA on mood and to conduct analyses on the temporal course of effects. Analyses revealed that exercise increased valence (beta = 0.023; P Exercise and NEA differed regarding their within-subject effects on mood, whereas exercise increased valence and calmness, NEA increased energetic arousal and decreased calmness. Therefore, it appears necessary to clearly differentiate between exercise and NEA regarding their within-subject effects on mood dimensions in both research and treatment.

  2. Variety of DNA Replication Activity Among Cyanobacteria Correlates with Distinct Respiration Activity in the Dark.

    Science.gov (United States)

    Ohbayashi, Ryudo; Yamamoto, Jun-Ya; Watanabe, Satoru; Kanesaki, Yu; Chibazakura, Taku; Miyagishima, Shin-Ya; Yoshikawa, Hirofumi

    2017-02-01

    Cyanobacteria exhibit light-dependent cell growth since most of their cellular energy is obtained by photosynthesis. In Synechococcus elongatus PCC 7942, one of the model cyanobacteria, DNA replication depends on photosynthetic electron transport. However, the critical signal for the regulatory mechanism of DNA replication has not been identified. In addition, conservation of this regulatory mechanism has not been investigated among cyanobacteria. To understand this regulatory signal and its dependence on light, we examined the regulation of DNA replication under both light and dark conditions among three model cyanobacteria, S. elongatus PCC 7942, Synechocystis sp. PCC 6803 and Anabaena sp. PCC 7120. Interestingly, DNA replication activity in Synechocystis and Anabaena was retained when cells were transferred to the dark, although it was drastically decreased in S. elongatus. Glycogen metabolism and respiration were higher in Synechocystis and Anabaena than in S. elongatus in the dark. Moreover, DNA replication activity in Synechocystis and Anabaena was reduced to the same level as that in S. elongatus by inhibition of respiratory electron transport after transfer to the dark. These results demonstrate that there is disparity in DNA replication occurring in the dark among cyanobacteria, which is caused by the difference in activity of respiratory electron transport. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  3. Distinctive Left Ventricular Activations Associated With ECG Pattern in Heart Failure Patients.

    Science.gov (United States)

    Derval, Nicolas; Duchateau, Josselin; Mahida, Saagar; Eschalier, Romain; Sacher, Frederic; Lumens, Joost; Cochet, Hubert; Denis, Arnaud; Pillois, Xavier; Yamashita, Seigo; Komatsu, Yuki; Ploux, Sylvain; Amraoui, Sana; Zemmoura, Adlane; Ritter, Philippe; Hocini, Mélèze; Haissaguerre, Michel; Jaïs, Pierre; Bordachar, Pierre

    2017-06-01

    In contrast to patients with left bundle branch block (LBBB), heart failure patients with narrow QRS and nonspecific intraventricular conduction delay (NICD) display a relatively limited response to cardiac resynchronization therapy. We sought to compare left ventricular (LV) activation patterns in heart failure patients with narrow QRS and NICD to patients with LBBB using high-density electroanatomic activation maps. Fifty-two heart failure patients (narrow QRS [n=18], LBBB [n=11], NICD [n=23]) underwent 3-dimensional electroanatomic mapping with a high density of mapping points (387±349 LV). Adjunctive scar imaging was available in 37 (71%) patients and was analyzed in relation to activation maps. LBBB patients typically demonstrated (1) a single LV breakthrough at the septum (38±15 ms post-QRS onset); (2) prolonged right-to-left transseptal activation with absence of direct LV Purkinje activity; (3) homogeneous propagation within the LV cavity; and (4) latest activation at the basal lateral LV. In comparison, both NICD and narrow QRS patients demonstrated (1) multiple LV breakthroughs along the posterior or anterior fascicles: narrow QRS versus LBBB, 5±2 versus 1±1; P =0.0004; NICD versus LBBB, 4±2 versus 1±1; P =0.001); (2) evidence of early/pre-QRS LV electrograms with Purkinje potentials; (3) rapid propagation in narrow QRS patients and more heterogeneous propagation in NICD patients; and (4) presence of limited areas of late activation associated with LV scar with high interindividual heterogeneity. In contrast to LBBB patients, narrow QRS and NICD patients are characterized by distinct mechanisms of LV activation, which may predict poor response to cardiac resynchronization therapy. © 2017 American Heart Association, Inc.

  4. SH3 Domains Differentially Stimulate Distinct Dynamin I Assembly Modes and G Domain Activity.

    Directory of Open Access Journals (Sweden)

    Sai Krishnan

    Full Text Available Dynamin I is a highly regulated GTPase enzyme enriched in nerve terminals which mediates vesicle fission during synaptic vesicle endocytosis. One regulatory mechanism involves its interactions with proteins containing Src homology 3 (SH3 domains. At least 30 SH3 domain-containing proteins bind dynamin at its proline-rich domain (PRD. Those that stimulate dynamin activity act by promoting its oligomerisation. We undertook a systematic parallel screening of 13 glutathione-S-transferase (GST-tagged endocytosis-related SH3 domains on dynamin binding, GTPase activity and oligomerisation. No correlation was found between dynamin binding and their potency to stimulate GTPase activity. There was limited correlation between the extent of their ability to stimulate dynamin activity and the level of oligomerisation, indicating an as yet uncharacterised allosteric coupling of the PRD and G domain. We examined the two variants, dynamin Iab and Ibb, which differ in the alternately splice middle domain α2 helix. They responded differently to the panel of SH3s, with the extent of stimulation between the splice variants varying greatly between the SH3s. This study reveals that SH3 binding can act as a heterotropic allosteric regulator of the G domain via the middle domain α2 helix, suggesting an involvement of this helix in communicating the PRD-mediated allostery. This indicates that SH3 binding both stabilises multiple conformations of the tetrameric building block of dynamin, and promotes assembly of dynamin-SH3 complexes with distinct rates of GTP hydrolysis.

  5. β1-adrenergic receptors activate two distinct signaling pathways in striatal neurons

    Science.gov (United States)

    Meitzen, John; Luoma, Jessie I.; Stern, Christopher M.; Mermelstein, Paul G.

    2010-01-01

    Monoamine action in the dorsal striatum and nucleus accumbens plays essential roles in striatal physiology. Although research often focuses on dopamine and its receptors, norepinephrine and adrenergic receptors are also crucial in regulating striatal function. While noradrenergic neurotransmission has been identified in the striatum, little is known regarding the signaling pathways activated by β-adrenergic receptors in this brain region. Using cultured striatal neurons, we characterized a novel signaling pathway by which activation of β1-adrenergic receptors leads to the rapid phosphorylation of cAMP Response Element Binding Protein (CREB), a transcription-factor implicated as a molecular switch underlying long-term changes in brain function. Norepinephrine-mediated CREB phosphorylation requires β1-adrenergic receptor stimulation of a receptor tyrosine kinase, ultimately leading to the activation of a Ras/Raf/MEK/MAPK/MSK signaling pathway. Activation of β1-adrenergic receptors also induces CRE-dependent transcription and increased c-fos expression. In addition, stimulation of β1-adrenergic receptors produces cAMP production, but surprisingly, β1-adrenergic receptor activation of adenylyl cyclase was not functionally linked to rapid CREB phosphorylation. These findings demonstrate that activation of β1-adrenergic receptors on striatal neurons can stimulate two distinct signaling pathways. These adrenergic actions can produce long-term changes in gene expression, as well as rapidly modulate cellular physiology. By elucidating the mechanisms by which norepinephrine and β1-adrenergic receptor activation affects striatal physiology, we provide the means to more fully understand the role of monoamines in modulating striatal function, specifically how norepinephrine and β1-adrenergic receptors may affect striatal physiology. PMID:21143600

  6. A chimeric prokaryotic pentameric ligand–gated channel reveals distinct pathways of activation

    Science.gov (United States)

    Schmandt, Nicolaus; Velisetty, Phanindra; Chalamalasetti, Sreevatsa V.; Stein, Richard A.; Bonner, Ross; Talley, Lauren; Parker, Mark D.; Mchaourab, Hassane S.; Yee, Vivien C.; Lodowski, David T.

    2015-01-01

    Recent high resolution structures of several pentameric ligand–gated ion channels have provided unprecedented details of their molecular architecture. However, the conformational dynamics and structural rearrangements that underlie gating and allosteric modulation remain poorly understood. We used a combination of electrophysiology, double electron–electron resonance (DEER) spectroscopy, and x-ray crystallography to investigate activation mechanisms in a novel functional chimera with the extracellular domain (ECD) of amine-gated Erwinia chrysanthemi ligand–gated ion channel, which is activated by primary amines, and the transmembrane domain of Gloeobacter violaceus ligand–gated ion channel, which is activated by protons. We found that the chimera was independently gated by primary amines and by protons. The crystal structure of the chimera in its resting state, at pH 7.0 and in the absence of primary amines, revealed a closed-pore conformation and an ECD that is twisted with respect to the transmembrane region. Amine- and pH-induced conformational changes measured by DEER spectroscopy showed that the chimera exhibits a dual mode of gating that preserves the distinct conformational changes of the parent channels. Collectively, our findings shed light on both conserved and divergent features of gating mechanisms in this class of channels, and will facilitate the design of better allosteric modulators. PMID:26415570

  7. Phosphorylation and nuclear accumulation are distinct events contributing to the activation of p53

    International Nuclear Information System (INIS)

    O'Hagan, Heather M.; Ljungman, Mats

    2004-01-01

    It has been recently shown that ionizing radiation (IR) and the mRNA synthesis inhibitor 5,6-dichloro-1-b-D-ribofuranosylbenzimidazole (DRB) act in synergy to induce p53-mediated transactivation of reporter plasmids in human cells [Oncogene 19 (2000) 3829]. We have extended these studies and show that ionizing radiation and DRB also act in synergy to induce ATM-mediated phosphorylation of the ser15 site of p53 and enhance the expression of endogenous p21 protein. Examination of the localization of p53 revealed that while DRB did not induce phosphorylation of the ser15 site of p53 but efficiently accumulated p53 in the nucleus, ionizing radiation induced phosphorylation of the ser15 site of p53 without prolonged nuclear accumulation. Importantly, the combination of DRB and IR resulted in a strong accumulation of phosphorylated p53 in the nucleus that was more persistent then p53 accumulation after IR alone. Furthermore, the nuclear export inhibitor leptomycin B showed a similar synergy with IR as did DRB regarding ser15 phosphorylation of p53 and p21 induction. These results suggest that the synergistic activation of the p53 response by the combination treatment is due to the activation of two distinct pathways where DRB causes the prolonged nuclear accumulation of p53 while ionizing radiation activates p53 by ATM-mediated phosphorylation

  8. Distinct effects of reminding mortality and physical pain on the default-mode activity and activity underlying self-reflection.

    Science.gov (United States)

    Shi, Zhenhao; Han, Shihui

    2018-06-01

    Behavioral research suggests that reminding both mortality and negative affect influences self-related thoughts. Using functional magnetic resonance imaging (MRI), we tested the hypothesis that reminders of mortality and physical pain decrease brain activity underlying self-related thoughts. Three groups of adults underwent priming procedures during which they answered questions pertaining to mortality, physical pain, or leisure time, respectively. Before and after priming, participants performed personality trait judgments on oneself or a celebrity, identified the font of words, or passively viewed a fixation. The default-mode activity and neural activity underlying self-reflection were identified by contrasting viewing a fixation vs. font judgment and trait judgments on oneself vs. a celebrity, respectively. The analyses of the pre-priming functional MRI (fMRI) data identified the default-mode activity in the posterior cingulate cortex (PCC), ventral medial prefrontal cortex (MPFC), and parahippocampal gyrus, and the activity underlying instructed self-reflection in both the ventral and dorsal regions of the MPFC. The analyses of the post-priming fMRI data revealed that, relative to leisure time priming, reminding mortality significantly reduced the default-mode PCC activity, and reminding physical pain significantly decreased the dorsal MPFC activity during instructed self-reflection. Our findings suggest distinct neural underpinnings of the effect of reminding morality and aversive emotion on default-mode and instructed self-reflection.

  9. Human activities cause distinct dissolved organic matter composition across freshwater ecosystems

    Science.gov (United States)

    Williams, Clayton J.; Frost, Paul C.; Morales-Williams, Ana M.; Larson, James H.; Richardson, William B.; Chiandet, Aisha S.; Xenopoulos, Marguerite A.

    2016-01-01

    Dissolved organic matter (DOM) composition in freshwater ecosystems is influenced by interactions between physical, chemical, and biological processes that are controlled, at one level, by watershed landscape, hydrology, and their connections. Against this environmental template, humans may strongly influence DOM composition. Yet, we lack a comprehensive understanding of DOM composition variation across freshwater ecosystems differentially affected by human activity. Using optical properties, we described DOM variation across five ecosystem groups of the Laurentian Great Lakes Region: large lakes, Kawartha Lakes, Experimental Lakes Area, urban stormwater ponds, and rivers (n = 184 sites). We determined how between ecosystem variation in DOM composition related to watershed size, land use and cover, water quality measures (conductivity, dissolved organic carbon (DOC), nutrient concentration, chlorophyll a), and human population density. The five freshwater ecosystem groups had distinctive DOM composition from each other. These significant differences were not explained completely through differences in watershed size nor spatial autocorrelation. Instead, multivariate partial least squares regression showed that DOM composition was related to differences in human impact across freshwater ecosystems. In particular, urban/developed watersheds with higher human population densities had a unique DOM composition with a clear anthropogenic influence that was distinct from DOM composition in natural land cover and/or agricultural watersheds. This nonagricultural, human developed impact on aquatic DOM was most evident through increased levels of a microbial, humic-like parallel factor analysis component (C6). Lotic and lentic ecosystems with low human population densities had DOM compositions more typical of clear water to humic-rich freshwater ecosystems but C6 was only present at trace to background levels. Consequently, humans are strongly altering the quality of DOM in

  10. Does the reading of different orthographies produce distinct brain activity patterns? An ERP study.

    Science.gov (United States)

    Bar-Kochva, Irit; Breznitz, Zvia

    2012-01-01

    Orthographies vary in the degree of transparency of spelling-sound correspondence. These range from shallow orthographies with transparent grapheme-phoneme relations, to deep orthographies, in which these relations are opaque. Only a few studies have examined whether orthographic depth is reflected in brain activity. In these studies a between-language design was applied, making it difficult to isolate the aspect of orthographic depth. In the present work this question was examined using a within-subject-and-language investigation. The participants were speakers of Hebrew, as they are skilled in reading two forms of script transcribing the same oral language. One form is the shallow pointed script (with diacritics), and the other is the deep unpointed script (without diacritics). Event-related potentials (ERPs) were recorded while skilled readers carried out a lexical decision task in the two forms of script. A visual non-orthographic task controlled for the visual difference between the scripts (resulting from the addition of diacritics to the pointed script only). At an early visual-perceptual stage of processing (~165 ms after target onset), the pointed script evoked larger amplitudes with longer latencies than the unpointed script at occipital-temporal sites. However, these effects were not restricted to orthographic processing, and may therefore have reflected, at least in part, the visual load imposed by the diacritics. Nevertheless, the results implied that distinct orthographic processing may have also contributed to these effects. At later stages (~340 ms after target onset) the unpointed script elicited larger amplitudes than the pointed one with earlier latencies. As this latency has been linked to orthographic-linguistic processing and to the classification of stimuli, it is suggested that these differences are associated with distinct lexical processing of a shallow and a deep orthography.

  11. Does the reading of different orthographies produce distinct brain activity patterns? An ERP study.

    Directory of Open Access Journals (Sweden)

    Irit Bar-Kochva

    Full Text Available Orthographies vary in the degree of transparency of spelling-sound correspondence. These range from shallow orthographies with transparent grapheme-phoneme relations, to deep orthographies, in which these relations are opaque. Only a few studies have examined whether orthographic depth is reflected in brain activity. In these studies a between-language design was applied, making it difficult to isolate the aspect of orthographic depth. In the present work this question was examined using a within-subject-and-language investigation. The participants were speakers of Hebrew, as they are skilled in reading two forms of script transcribing the same oral language. One form is the shallow pointed script (with diacritics, and the other is the deep unpointed script (without diacritics. Event-related potentials (ERPs were recorded while skilled readers carried out a lexical decision task in the two forms of script. A visual non-orthographic task controlled for the visual difference between the scripts (resulting from the addition of diacritics to the pointed script only. At an early visual-perceptual stage of processing (~165 ms after target onset, the pointed script evoked larger amplitudes with longer latencies than the unpointed script at occipital-temporal sites. However, these effects were not restricted to orthographic processing, and may therefore have reflected, at least in part, the visual load imposed by the diacritics. Nevertheless, the results implied that distinct orthographic processing may have also contributed to these effects. At later stages (~340 ms after target onset the unpointed script elicited larger amplitudes than the pointed one with earlier latencies. As this latency has been linked to orthographic-linguistic processing and to the classification of stimuli, it is suggested that these differences are associated with distinct lexical processing of a shallow and a deep orthography.

  12. D4 receptor deficiency in mice has limited effects on impulsivity and novelty seeking.

    Science.gov (United States)

    Helms, C M; Gubner, N R; Wilhelm, C J; Mitchell, S H; Grandy, D K

    2008-09-01

    Alleles of the human dopamine D(4) receptor (D(4)R) gene (DRD4.7) have repeatedly been found to correlate with novelty seeking, substance abuse, pathological gambling, and attention-deficit hyperactivity disorder (ADHD). If these various psychopathologies are a result of attenuated D(4)R-mediated signaling, mice lacking D(4)Rs (D(4)KO) should be more impulsive than wild-type (WT) mice and exhibit more novelty seeking. However, in our study, D(4)KO and WT mice showed similar levels of impulsivity as measured by delay discounting performance and response inhibition on a Go/No-go test, suggesting that D(4)R-mediated signaling may not affect impulsivity. D(4)KO mice were more active than WT mice in the first 5 min of a novel open field test, suggesting greater novelty seeking. For both genotypes, more impulsive mice habituated less in the novel open field. These data suggest that the absence of D(4)Rs is not sufficient to cause psychopathologies associated with heightened impulsivity and novelty seeking.

  13. Staphylokinase has distinct modes of interaction with antimicrobial peptides, modulating its plasminogen-activation properties

    Science.gov (United States)

    Nguyen, Leonard T.; Vogel, Hans J.

    2016-01-01

    Staphylokinase (Sak) is a plasminogen activator protein that is secreted by many Staphylococcus aureus strains. Sak also offers protection by binding and inhibiting specific antimicrobial peptides (AMPs). Here, we evaluate Sak as a more general interaction partner for AMPs. Studies with melittin, mCRAMP, tritrpticin and bovine lactoferricin indicate that the truncation of the first ten residues of Sak (SakΔN10), which occurs in vivo and uncovers important residues in a bulge region, improves its affinity for AMPs. Melittin and mCRAMP have a lower affinity for SakΔN10, and in docking studies, they bind to the N-terminal segment and bulge region of SakΔN10. By comparison, lactoferricin and tritrpticin form moderately high affinity 1:1 complexes with SakΔN10 and their cationic residues form several electrostatic interactions with the protein’s α-helix. Overall, our work identifies two distinct AMP binding surfaces on SakΔN10 whose occupation would lead to either inhibition or promotion of its plasminogen activating properties. PMID:27554435

  14. Generation of biologically active endostatin fragments from human collagen XVIII by distinct matrix metalloproteases

    International Nuclear Information System (INIS)

    Heljasvaara, Ritva; Nyberg, Pia; Luostarinen, Jani; Parikka, Mataleena; Heikkilae, Pia; Rehn, Marko; Sorsa, Timo; Salo, Tuula; Pihlajaniemi, Taina

    2005-01-01

    Endostatin, a potent inhibitor of endothelial cell proliferation, migration, angiogenesis and tumor growth, is proteolytically cleaved from the C-terminal noncollagenous NC1 domain of type XVIII collagen. We investigated the endostatin formation from human collagen XVIII by several MMPs in vitro. The generation of endostatin fragments differing in molecular size (24-30 kDa) and in N-terminal sequences was identified in the cases of MMP-3, -7, -9, -13 and -20. The cleavage sites were located in the protease-sensitive hinge region between the trimerization and endostatin domains of NC1. MMP-1, -2, -8 and -12 did not show any significant activity against the C-terminus of collagen XVIII. The anti-proliferative effect of the 20-kDa endostatin, three longer endostatin-containing fragments generated in vitro by distinct MMPs and the entire NC1 domain, on bFGF-stimulated human umbilical vein endothelial cells was established. The anti-migratory potential of some of these fragments was also studied. In addition, production of endostatin fragments between 24-30 kDa by human hepatoblastoma cells was shown to be due to MMP action on type XVIII collagen. Our results indicate that certain, especially cancer-related, MMP family members can generate biologically active endostatin-containing polypeptides from collagen XVIII and thus, by releasing endostatin fragments, may participate in the inhibition of endothelial cell proliferation, migration and angiogenesis

  15. Legal distinction between employee and independent contractor as applied to collective bargaining activities in timber harvesting

    Science.gov (United States)

    James E. Granskog; William C. Siegal

    1977-01-01

    Collective bargaining attempts by timber harvesting labor groups is often complicated by lack of a clear legal distinction between "employees" and "independent contractors." the primary criterion to make the distinction - the "right-to-control" test of common law - has now been amplified by a number of secondary tests, including: 1) the...

  16. Elevation of D4 dopamine receptor mRNA in postmortem schizophrenic brain.

    Science.gov (United States)

    Stefanis, N C; Bresnick, J N; Kerwin, R W; Schofield, W N; McAllister, G

    1998-01-01

    The D4 dopamine (DA) receptor has been proposed to be a target for the development of a novel antipsychotic drug based on its pharmacological and distribution profile. There is much interest in whether D4 DA receptor levels are altered in schizophrenia, but the lack of an available receptor subtype-specific radioligand made this difficult to quantitate. In this study, we examined whether D4 mRNA levels are altered in different brain regions of schizophrenics compared to controls. Ribonuclease protection assays were carried out on total RNA samples isolated postmortem from frontal cortex and caudate brain regions of schizophrenics and matched controls. 32P-labelled RNA probes to the D4 DA receptor and to the housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase (G3PDH), were hybridised with the RNA samples, digested with ribonucleases to remove unhybridised probe, and separated on 6% sequencing gels. Densitometer analysis on the subsequent autoradiogams was used to calculate the relative optical density of D4 mRNA compared to G3PDH mRNA. Statistical analysis of the data revealed a 3-fold higher level (P<0.011) of D4 mRNA in the frontal cortex of schizophrenics compared to controls. No increase was seen in caudate. D4 receptors could play a role in mediating dopaminergic activity in frontal cortex, an activity which may be malfunctioning in schizophrenia.

  17. Vitamin D activation of functionally distinct regulatory miRNAs in primary human osteoblasts.

    Science.gov (United States)

    Lisse, Thomas S; Chun, Rene F; Rieger, Sandra; Adams, John S; Hewison, Martin

    2013-06-01

    When bound to the vitamin D receptor (VDR), the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D) is a potent regulator of osteoblast transcription. Less clear is the impact of 1,25D on posttranscriptional events in osteoblasts, such as the generation and action of microRNAs (miRNAs). Microarray analysis using replicate (n = 3) primary cultures of human osteoblasts (HOBs) identified human miRNAs that were differentially regulated by >1.5-fold following treatment with 1,25D (10 nM, 6 hours), which included miRNAs 637 and 1228. Quantitative reverse transcription PCR analyses showed that the host gene for miR-1228, low-density lipoprotein receptor-related protein 1 (LRP1), was coinduced with miR-1228 in a dose-dependent fashion following treatment with 1,25D (0.1-10 nM, 6 hours). By contrast, the endogenous host gene for miR-637, death-associated protein kinase 3 (DAPK3), was transcriptionally repressed by following treatment with 1,25D. Analysis of two potential targets for miR-637 and miR-1228 in HOB, type IV collagen (COL4A1) and bone morphogenic protein 2 kinase (BMP2K), respectively, showed that 1,25D-mediates suppression of these targets via distinct mechanisms. In the case of miR-637, suppression of COL4A1 appears to occur via decreased levels of COL4A1 mRNA. By contrast, suppression of BMP2K by miR-1228 appears to occur by inhibition of protein translation. In mature HOBs, small interfering RNA (siRNA) inactivation of miR-1228 alone was sufficient to abrogate 1,25D-mediated downregulation of BMP2K protein expression. This was associated with suppression of prodifferentiation responses to 1,25D in HOB, as represented by parallel decrease in osteocalcin and alkaline phosphatase expression. These data show for the first time that the effects of 1,25D on human bone cells are not restricted to classical VDR-mediated transcriptional responses but also involve miRNA-directed posttranscriptional mechanisms. Copyright © 2013 American Society for Bone and

  18. A direct comparison of appetitive and aversive anticipation: Overlapping and distinct neural activation.

    Science.gov (United States)

    Sege, Christopher T; Bradley, Margaret M; Weymar, Mathias; Lang, Peter J

    2017-05-30

    fMRI studies of reward find increased neural activity in ventral striatum and medial prefrontal cortex (mPFC), whereas other regions, including the dorsolateral prefrontal cortex (dlPFC), anterior cingulate cortex (ACC), and anterior insula, are activated when anticipating aversive exposure. Although these data suggest differential activation during anticipation of pleasant or of unpleasant exposure, they also arise in the context of different paradigms (e.g., preparation for reward vs. threat of shock) and participants. To determine overlapping and unique regions active during emotional anticipation, we compared neural activity during anticipation of pleasant or unpleasant exposure in the same participants. Cues signalled the upcoming presentation of erotic/romantic, violent, or everyday pictures while BOLD activity during the 9-s anticipatory period was measured using fMRI. Ventral striatum and a ventral mPFC subregion were activated when anticipating pleasant, but not unpleasant or neutral, pictures, whereas activation in other regions was enhanced when anticipating appetitive or aversive scenes. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Distinct requirements for activation of NKT and NK cells during viral infection.

    Science.gov (United States)

    Tyznik, Aaron J; Verma, Shilpi; Wang, Qiao; Kronenberg, Mitchell; Benedict, Chris A

    2014-04-15

    NK cells are key regulators of innate defense against mouse CMV (MCMV). Like NK cells, NKT cells also produce high levels of IFN-γ rapidly after MCMV infection. However, whether similar mechanisms govern activation of these two cell types, as well as the significance of NKT cells for host resistance, remain unknown. In this article, we show that, although both NKT and NK cells are activated via cytokines, their particular cytokine requirements differ significantly in vitro and in vivo. IL-12 is required for NKT cell activation in vitro but is not sufficient, whereas NK cells have the capacity to be activated more promiscuously in response to individual cytokines from innate cells. In line with these results, GM-CSF-derived dendritic cells activated only NK cells upon MCMV infection, consistent with their virtual lack of IL-12 production, whereas Flt3 ligand-derived dendritic cells produced IL-12 and activated both NK and NKT cells. In vivo, NKT cell activation was abolished in IL-12(-/-) mice infected with MCMV, whereas NK cells were still activated. In turn, splenic NK cell activation was more IL-18 dependent. The differential requirements for IL-12 and IL-18 correlated with the levels of cytokine receptor expression by NK and NKT cells. Finally, mice lacking NKT cells showed reduced control of MCMV, and depleting NK cells further enhanced viral replication. Taken together, our results show that NKT and NK cells have differing requirements for cytokine-mediated activation, and both can contribute nonredundantly to MCMV defense, revealing that these two innate lymphocyte subsets function together to fine-tune antiviral responses.

  20. Modification of Pulsed Electric Field Conditions Results in Distinct Activation Profiles of Platelet-Rich Plasma.

    Directory of Open Access Journals (Sweden)

    Andrew L Frelinger

    Full Text Available Activated autologous platelet-rich plasma (PRP used in therapeutic wound healing applications is poorly characterized and standardized. Using pulsed electric fields (PEF to activate platelets may reduce variability and eliminate complications associated with the use of bovine thrombin. We previously reported that exposing PRP to sub-microsecond duration, high electric field (SMHEF pulses generates a greater number of platelet-derived microparticles, increased expression of prothrombotic platelet surfaces, and differential release of growth factors compared to thrombin. Moreover, the platelet releasate produced by SMHEF pulses induced greater cell proliferation than plasma.To determine whether sub-microsecond duration, low electric field (SMLEF bipolar pulses results in differential activation of PRP compared to SMHEF, with respect to profiles of activation markers, growth factor release, and cell proliferation capacity.PRP activation by SMLEF bipolar pulses was compared to SMHEF pulses and bovine thrombin. PRP was prepared using the Harvest SmartPreP2 System from acid citrate dextrose anticoagulated healthy donor blood. PEF activation by either SMHEF or SMLEF pulses was performed using a standard electroporation cuvette preloaded with CaCl2 and a prototype instrument designed to take into account the electrical properties of PRP. Flow cytometry was used to assess platelet surface P-selectin expression, and annexin V binding. Platelet-derived growth factor (PDGF, vascular endothelial growth factor (VEGF, endothelial growth factor (EGF and platelet factor 4 (PF4, and were measured by ELISA. The ability of supernatants to stimulate proliferation of human epithelial cells in culture was also evaluated. Controls included vehicle-treated, unactivated PRP and PRP with 10 mM CaCl2 activated with 1 U/mL bovine thrombin.PRP activated with SMLEF bipolar pulses or thrombin had similar light scatter profiles, consistent with the presence of platelet

  1. Modification of Pulsed Electric Field Conditions Results in Distinct Activation Profiles of Platelet-Rich Plasma.

    Science.gov (United States)

    Frelinger, Andrew L; Gerrits, Anja J; Garner, Allen L; Torres, Andrew S; Caiafa, Antonio; Morton, Christine A; Berny-Lang, Michelle A; Carmichael, Sabrina L; Neculaes, V Bogdan; Michelson, Alan D

    2016-01-01

    Activated autologous platelet-rich plasma (PRP) used in therapeutic wound healing applications is poorly characterized and standardized. Using pulsed electric fields (PEF) to activate platelets may reduce variability and eliminate complications associated with the use of bovine thrombin. We previously reported that exposing PRP to sub-microsecond duration, high electric field (SMHEF) pulses generates a greater number of platelet-derived microparticles, increased expression of prothrombotic platelet surfaces, and differential release of growth factors compared to thrombin. Moreover, the platelet releasate produced by SMHEF pulses induced greater cell proliferation than plasma. To determine whether sub-microsecond duration, low electric field (SMLEF) bipolar pulses results in differential activation of PRP compared to SMHEF, with respect to profiles of activation markers, growth factor release, and cell proliferation capacity. PRP activation by SMLEF bipolar pulses was compared to SMHEF pulses and bovine thrombin. PRP was prepared using the Harvest SmartPreP2 System from acid citrate dextrose anticoagulated healthy donor blood. PEF activation by either SMHEF or SMLEF pulses was performed using a standard electroporation cuvette preloaded with CaCl2 and a prototype instrument designed to take into account the electrical properties of PRP. Flow cytometry was used to assess platelet surface P-selectin expression, and annexin V binding. Platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), endothelial growth factor (EGF) and platelet factor 4 (PF4), and were measured by ELISA. The ability of supernatants to stimulate proliferation of human epithelial cells in culture was also evaluated. Controls included vehicle-treated, unactivated PRP and PRP with 10 mM CaCl2 activated with 1 U/mL bovine thrombin. PRP activated with SMLEF bipolar pulses or thrombin had similar light scatter profiles, consistent with the presence of platelet

  2. Locomotor activity: A distinctive index in morphine self-administration in rats

    OpenAIRE

    Zhang, Jian-Jun; Kong, Qingyao

    2017-01-01

    Self-administration of addictive drugs is a widely used tool for studying behavioral, neurobiological, and genetic factors in addiction. However, how locomotor activity is affected during self-administration of addictive drugs has not been extensively studied. In our present study, we tested the locomotor activity levels during acquisition, extinction and reinstatement of morphine self-administration in rats. We found that compared with saline self-administration (SA), rats that trained with ...

  3. Distinct microbial communities in the active and permafrost layers on the Tibetan Plateau.

    Science.gov (United States)

    Chen, Yong-Liang; Deng, Ye; Ding, Jin-Zhi; Hu, Hang-Wei; Xu, Tian-Le; Li, Fei; Yang, Gui-Biao; Yang, Yuan-He

    2017-12-01

    Permafrost represents an important understudied genetic resource. Soil microorganisms play important roles in regulating biogeochemical cycles and maintaining ecosystem function. However, our knowledge of patterns and drivers of permafrost microbial communities is limited over broad geographic scales. Using high-throughput Illumina sequencing, this study compared soil bacterial, archaeal and fungal communities between the active and permafrost layers on the Tibetan Plateau. Our results indicated that microbial alpha diversity was significantly higher in the active layer than in the permafrost layer with the exception of fungal Shannon-Wiener index and Simpson's diversity index, and microbial community structures were significantly different between the two layers. Our results also revealed that environmental factors such as soil fertility (soil organic carbon, dissolved organic carbon and total nitrogen contents) were the primary drivers of the beta diversity of bacterial, archaeal and fungal communities in the active layer. In contrast, environmental variables such as the mean annual precipitation and total phosphorus played dominant roles in driving the microbial beta diversity in the permafrost layer. Spatial distance was important for predicting the bacterial and archaeal beta diversity in both the active and permafrost layers, but not for fungal communities. Collectively, these results demonstrated different driving factors of microbial beta diversity between the active layer and permafrost layer, implying that the drivers of the microbial beta diversity observed in the active layer cannot be used to predict the biogeographic patterns of the microbial beta diversity in the permafrost layer. © 2017 John Wiley & Sons Ltd.

  4. A DISTINCTIVE DISK-JET COUPLING IN THE SEYFERT-1 ACTIVE GALACTIC NUCLEUS NGC 4051

    International Nuclear Information System (INIS)

    King, A. L.; Miller, J. M.; Gueltekin, K.; Reynolds, M. T.; Cackett, E. M.; Fabian, A. C.; Markoff, S.; Nowak, M. A.; Rupen, M.

    2011-01-01

    We report on the results of a simultaneous monitoring campaign employing eight Chandra X-ray (0.5-10 keV) and six Very Large Array/Extended Very Large Array (8.4 GHz) radio observations of NGC 4051 over seven months. Evidence for compact jets is observed in the 8.4 GHz radio band; this builds on mounting evidence that jet production may be prevalent even in radio-quiet Seyferts. Assuming comparatively negligible local diffuse emission in the nucleus, the results also demonstrate an inverse correlation of L radio ∝ L -0.72±0.04 X-ray . If the A configuration is excluded in the case where diffuse emission plays a significant role, the relation is still L radio ∝ L X-ray -0.12±0.05 . Current research linking the mass of supermassive black holes and stellar-mass black holes in the 'low/hard' state to X-ray luminosities and radio luminosities suggests a 'fundamental plane of accretion onto black holes' that has a positive correlation of L radio ∝ L 0.67±0.12 X-ray . Our simultaneous results differ from this relation by more than 11σ (6σ excluding the A configuration), indicating that a separate mode of accretion and ejection may operate in this system. A review of the literature shows that the inverse correlation seen in NGC 4051 is seen in three other black hole systems, all of which accrete at near 10% of their Eddington luminosity, perhaps suggesting a distinct mode of disk-jet coupling at high Eddington fractions. We discuss our results in the context of disks and jets in black holes and accretion across the black hole mass scale.

  5. Dectin-1 isoforms contribute to distinct Th1/Th17 cell activation in mucosal candidiasis

    Science.gov (United States)

    Carvalho, Agostinho; Giovannini, Gloria; De Luca, Antonella; D'Angelo, Carmen; Casagrande, Andrea; Iannitti, Rossana G; Ricci, Giovanni; Cunha, Cristina; Romani, Luigina

    2012-01-01

    The recognition of β-glucans by dectin-1 has been shown to mediate cell activation, cytokine production and a variety of antifungal responses. Here, we report that the functional activity of dectin-1 in mucosal immunity to Candida albicans is influenced by the genetic background of the host. Dectin-1 was required for the proper control of gastrointestinal and vaginal candidiasis in C57BL/6, but not BALB/c mice; in fact, the latter showed increased resistance in the absence of dectin-1. The susceptibility of dectin-1-deficient C57BL/6 mice to infection was associated with defects in IL-17A and aryl hydrocarbon receptor-dependent IL-22 production and in adaptive Th1 responses. In contrast, the resistance of dectin-1-deficient BALB/c mice was associated with increased IL-17A and IL-22 production and the skewing towards Th1/Treg immune responses that provide immunological memory. Disparate canonical/noncanonical NF-κB signaling pathways downstream of dectin-1 were activated in the two different mouse strains. Thus, the net activity of dectin-1 in antifungal mucosal immunity is dependent on the host's genetic background, which affects both the innate cytokine production and the adaptive Th1/Th17 cell activation upon dectin-1 signaling. PMID:22543832

  6. Mechanisms of distinct activated carbon and biochar amendment effects on petroleum vapour biofiltration in soil.

    Science.gov (United States)

    Bushnaf, Khaled M; Mangse, George; Meynet, Paola; Davenport, Russell J; Cirpka, Olaf A; Werner, David

    2017-10-18

    We studied the effects of two percent by weight activated carbon versus biochar amendments in 93 cm long sand columns on the biofiltration of petroleum vapours released by a non-aqueous phase liquid (NAPL) source. Activated carbon greatly enhanced, whereas biochar slightly reduced, the biofiltration of volatile petroleum hydrocarbons (VPHs) over 430 days. Sorbent amendment benefitted the VPH biofiltration by retarding breakthrough during the biodegradation lag phase. Subsequently, sorbent amendment briefly reduced the mineralization of petroleum hydrocarbons by limiting their bioavailability. During the last and longest study period, when conditions became less supportive of microbial growth, because of inorganic nutrient scarcity, the sorbents again improved the pollution attenuation by preventing the degrading microorganisms from being overloaded with VPHs. A 16S rRNA gene based analysis showed sorbent amendment effects on soil microbial communities. Nocardioidaceae benefitted the most from petroleum hydrocarbons in activated carbon amended soil, whereas Pseudomonadacea predominated in unamended soil. Whilst the degrading microorganisms were overloaded with VPHs in the unamended soil, the reduced mobility and bioavailability of VPHs in the activated carbon amended soil led to the emergence of communities with higher specific substrate affinity, which removed bioavailable VPHs effectively at low concentrations. A numerical pollutant fate model reproduced these experimental observations by considering sorption effects on the pollutant migration and bioavailability for growth of VPH degrading biomass, which is limited by a maximum soil biomass carrying capacity. Activated carbon was a much stronger sorbent for VPHs than biochar, which explained the diverging effects of the two sorbents in this study.

  7. Cyclic lipopeptides from Bacillus subtilis activate distinct patterns of defence responses in grapevine.

    Science.gov (United States)

    Farace, Giovanni; Fernandez, Olivier; Jacquens, Lucile; Coutte, François; Krier, François; Jacques, Philippe; Clément, Christophe; Barka, Essaid Ait; Jacquard, Cédric; Dorey, Stéphan

    2015-02-01

    Non-self-recognition of microorganisms partly relies on the perception of microbe-associated molecular patterns (MAMPs) and leads to the activation of an innate immune response. Bacillus subtilis produces three main families of cyclic lipopeptides (LPs), namely surfactins, iturins and fengycins. Although LPs are involved in induced systemic resistance (ISR) activation, little is known about defence responses induced by these molecules and their involvement in local resistance to fungi. Here, we showed that purified surfactin, mycosubtilin (iturin family) and plipastatin (fengycin family) are perceived by grapevine plant cells. Although surfactin and mycosubtilin stimulated grapevine innate immune responses, they differentially activated early signalling pathways and defence gene expression. By contrast, plipastatin perception by grapevine cells only resulted in early signalling activation. Gene expression analysis suggested that mycosubtilin activated salicylic acid (SA) and jasmonic acid (JA) signalling pathways, whereas surfactin mainly induced an SA-regulated response. Although mycosubtilin and plipastatin displayed direct antifungal activity, only surfactin and mycosubtilin treatments resulted in a local long-lasting enhanced tolerance to the necrotrophic fungus Botrytis cinerea in grapevine leaves. Moreover, challenge with specific strains overproducing surfactin and mycosubtilin led to a slightly enhanced stimulation of the defence response compared with the LP-non-producing strain of B. subtilis. Altogether, our results provide the first comprehensive view of the involvement of LPs from B. subtilis in grapevine plant defence and local resistance against the necrotrophic pathogen Bo. cinerea. Moreover, this work is the first to highlight the ability of mycosubtilin to trigger an immune response in plants. © 2014 BSPP AND JOHN WILEY & SONS LTD.

  8. Distinct migration and contact dynamics of resting and IL-2-activated human natural killer cells

    Directory of Open Access Journals (Sweden)

    Per Erik Olofsson

    2014-03-01

    Full Text Available Natural killer (NK cells serve as one of the first lines of defense against viral infections and transformed cells. NK cell cytotoxicity is not dependent on antigen presentation by target cells, but is dependent on integration of activating and inhibitory signals triggered by receptor–ligand interactions formed at a tight intercellular contact between the NK and target cell, i.e. the immune synapse. We have studied the single-cell migration behavior and target-cell contact dynamics of resting and IL-2-activated human peripheral blood NK cells. Small populations of NK cells and target cells were confined in microwells and imaged by fluorescence microscopy for >8 h. Only the IL-2-activated population of NK cells showed efficient cytotoxicity against the human embryonic kidney (HEK 293T target cells. We found that although the average migration speeds were comparable, activated NK cells showed significantly more dynamic migration behavior, with more frequent transitions between periods of low and high motility. Resting NK cells formed fewer and weaker contacts with target cells, which manifested as shorter conjugation times and in many cases a complete lack of post-conjugation attachment to target cells. Activated NK cells were approximately twice as big as the resting cells, displayed a more migratory phenotype, and were more likely to employ motile scanning of the target cell surface during conjugation. Taken together, our experiments quantify, at the single-cell level, how activation by IL-2 leads to altered NK cell cytotoxicity, migration behavior and contact dynamics.

  9. Distinct neural pathways mediate alpha7 nicotinic acetylcholine receptor-dependent activation of the forebrain

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hay-Schmidt, Anders; Hansen, Henrik H

    2010-01-01

    alpha(7) nicotinic acetylcholine receptor (nAChR) agonists are candidates for the treatment of cognitive deficits in schizophrenia. Selective alpha(7) nAChR agonists, such as SSR180711, activate neurons in the medial prefrontal cortex (mPFC) and nucleus accumbens shell (ACCshell) in rats, regions...

  10. Context Fear Learning Specifically Activates Distinct Populations of Neurons in Amygdala and Hypothalamus

    Science.gov (United States)

    Trogrlic, Lidia; Wilson, Yvette M.; Newman, Andrew G.; Murphy, Mark

    2011-01-01

    The identity and distribution of neurons that are involved in any learning or memory event is not known. In previous studies, we identified a discrete population of neurons in the lateral amygdala that show learning-specific activation of a c-"fos"-regulated transgene following context fear conditioning. Here, we have extended these studies to…

  11. Distinct conformational changes in activated agonist-bound and agonist-free glycine receptor subunits

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Lynch, Joseph W

    2009-01-01

    Ligand binding to Cys-loop receptors produces either global conformational changes that lead to activation or local conformational changes that do not. We found that the fluorescence of a fluorophore tethered to R271C in the extracellular M2 region of the alpha1 glycine receptor increases during ...

  12. Comparison of mitochondrial and nucleolar RNase MRP reveals identical RNA components with distinct enzymatic activities and protein components.

    Science.gov (United States)

    Lu, Qiaosheng; Wierzbicki, Sara; Krasilnikov, Andrey S; Schmitt, Mark E

    2010-03-01

    RNase MRP is a ribonucleoprotein endoribonuclease found in three cellular locations where distinct substrates are processed: the mitochondria, the nucleolus, and the cytoplasm. Cytoplasmic RNase MRP is the nucleolar enzyme that is transiently relocalized during mitosis. Nucleolar RNase MRP (NuMRP) was purified to homogeneity, and we extensively purified the mitochondrial RNase MRP (MtMRP) to a single RNA component identical to the NuMRP RNA. Although the protein components of the NuMRP were identified by mass spectrometry successfully, none of the known NuMRP proteins were found in the MtMRP preparation. Only trace amounts of the core NuMRP protein, Pop4, were detected in MtMRP by Western blot. In vitro activity of the two enzymes was compared. MtMRP cleaved only mitochondrial ORI5 substrate, while NuMRP cleaved all three substrates. However, the NuMRP enzyme cleaved the ORI5 substrate at sites different than the MtMRP enzyme. In addition, enzymatic differences in preferred ionic strength confirm these enzymes as distinct entities. Magnesium was found to be essential to both enzymes. We tested a number of reported inhibitors including puromycin, pentamidine, lithium, and pAp. Puromycin inhibition suggested that it binds directly to the MRP RNA, reaffirming the role of the RNA component in catalysis. In conclusion, our study confirms that the NuMRP and MtMRP enzymes are distinct entities with differing activities and protein components but a common RNA subunit, suggesting that the RNA must be playing a crucial role in catalytic activity.

  13. Distinct patterns of constitutive phosphodiesterase activity in mouse sinoatrial node and atrial myocardium.

    Directory of Open Access Journals (Sweden)

    Rui Hua

    Full Text Available Phosphodiesterases (PDEs are critical regulators of cyclic nucleotides in the heart. In ventricular myocytes, the L-type Ca(2+ current (I(Ca,L is a major target of regulation by PDEs, particularly members of the PDE2, PDE3 and PDE4 families. Conversely, much less is known about the roles of PDE2, PDE3 and PDE4 in the regulation of action potential (AP properties and I(Ca,L in the sinoatrial node (SAN and the atrial myocardium, especially in mice. Thus, the purpose of our study was to measure the effects of global PDE inhibition with Isobutyl-1-methylxanthine (IBMX and selective inhibitors of PDE2, PDE3 and PDE4 on AP properties in isolated mouse SAN and right atrial myocytes. We also measured the effects of these inhibitors on I(Ca,L in SAN and atrial myocytes in comparison to ventricular myocytes. Our data demonstrate that IBMX markedly increases spontaneous AP frequency in SAN myocytes and AP duration in atrial myocytes. Spontaneous AP firing in SAN myocytes was also increased by the PDE2 inhibitor erythro-9-[2-hydroxy-3-nonyl] adenine (EHNA, the PDE3 inhibitor milrinone (Mil and the PDE4 inhibitor rolipram (Rol. In contrast, atrial AP duration was increased by EHNA and Rol, but not by Mil. IBMX also potently, and similarly, increased I(Ca,L in SAN, atrial and ventricular myocytes; however, important differences emerged in terms of which inhibitors could modulate I(Ca,L in each myocyte type. Consistent with our AP measurements, EHNA, Mil and Rol each increased I(Ca,L in SAN myocytes. Also, EHNA and Rol, but not Mil, increased atrial I(Ca,L. In complete contrast, no selective PDE inhibitors increased I(Ca,L in ventricular myocytes when given alone. Thus, our data show that the effects of selective PDE2, PDE3 and PDE4 inhibitors are distinct in the different regions of the myocardium indicating important differences in how each PDE family constitutively regulates ion channel function in the SAN, atrial and ventricular myocardium.

  14. Distinct BOLD activation profiles following central and peripheral oxytocin administration in awake rats

    Directory of Open Access Journals (Sweden)

    Craig F Ferris

    2015-09-01

    Full Text Available A growing body of literature has suggested that intranasal oxytocin (OT or other systemic routes of administration can alter prosocial behavior, presumably by directly activating OT sensitive neural circuits in the brain. Yet there is no clear evidence that OT given peripherally can cross the blood-brain-barrier at levels sufficient to engage the OT receptor. To address this issue we examined changes in blood oxygen level dependent (BOLD signal intensity in response to peripheral OT injections (0.1, 0.5 or 2.5 mg/kg during functional magnetic resonance (fMRI in awake rats imaged at 7.0 tesla. These data were compared to OT (1ug/5 µl given directly to the brain via the lateral cerebroventricle. Using a 3D annotated MRI atlas of the rat brain segmented into 171 brain areas and computational analysis we reconstructed the distributed integrated neural circuits identified with BOLD fMRI following central and peripheral OT. Both routes of administration caused significant changes in BOLD signal within the first 10 min of administration. As expected, central OT activated a majority of brain areas known to express a high density of OT receptors e.g., lateral septum, subiculum, shell of the accumbens, bed nucleus of the stria terminalis. This profile of activation was not matched by peripheral OT. The change in BOLD signal to peripheral OT did not show any discernible dose-response. Interestingly, peripheral OT affected all subdivisions of the olfactory bulb, in addition to the cerebellum and several brainstem areas relevant to the autonomic nervous system, including the solitary tract nucleus. The results from this imaging study do not support a direct central action of peripheral OT on the brain. Instead, the patterns of brain activity suggest that peripheral OT may interact at the level of the olfactory bulb and through sensory afferents from the autonomic nervous system to influence brain activity.

  15. A distinct regulatory region of the Bmp5 locus activates gene expression following adult bone fracture or soft tissue injury.

    Science.gov (United States)

    Guenther, Catherine A; Wang, Zhen; Li, Emma; Tran, Misha C; Logan, Catriona Y; Nusse, Roel; Pantalena-Filho, Luiz; Yang, George P; Kingsley, David M

    2015-08-01

    Bone morphogenetic proteins (BMPs) are key signaling molecules required for normal development of bones and other tissues. Previous studies have shown that null mutations in the mouse Bmp5 gene alter the size, shape and number of multiple bone and cartilage structures during development. Bmp5 mutations also delay healing of rib fractures in adult mutants, suggesting that the same signals used to pattern embryonic bone and cartilage are also reused during skeletal regeneration and repair. Despite intense interest in BMPs as agents for stimulating bone formation in clinical applications, little is known about the regulatory elements that control developmental or injury-induced BMP expression. To compare the DNA sequences that activate gene expression during embryonic bone formation and following acute injuries in adult animals, we assayed regions surrounding the Bmp5 gene for their ability to stimulate lacZ reporter gene expression in transgenic mice. Multiple genomic fragments, distributed across the Bmp5 locus, collectively coordinate expression in discrete anatomic domains during normal development, including in embryonic ribs. In contrast, a distinct regulatory region activated expression following rib fracture in adult animals. The same injury control region triggered gene expression in mesenchymal cells following tibia fracture, in migrating keratinocytes following dorsal skin wounding, and in regenerating epithelial cells following lung injury. The Bmp5 gene thus contains an "injury response" control region that is distinct from embryonic enhancers, and that is activated by multiple types of injury in adult animals. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Distinct regions in the C-Terminus required for GLP-1R cell surface expression, activity and internalisation.

    Science.gov (United States)

    Thompson, Aiysha; Kanamarlapudi, Venkateswarlu

    2015-09-15

    The glucagon-like peptide-1 (GLP-1) receptor (GLP-1R), an important drug target in the treatment of type 2 diabetes, is a G-protein coupled receptor (GPCR) that mediates insulin secretion by GLP-1. The N-terminus controls GLP-1R biosynthetic trafficking to the cell surface but the C-terminus involvement in that trafficking is unknown. The aim of this study was to identify distinct regions within the C-terminal domain required for human GLP-1R (hGLP-1R) cell surface expression, activity and internalisation using a number of C-terminal deletions and site-directed mutations. The results of this study revealed that the residues 411-418 within the C-terminal domain of the hGLP-1R are critical in targeting the newly synthesised receptor to the plasma membrane. The residues 419-430 are important for cAMP producing activity of the receptor, most likely by coupling to Gαs. However, the residues 431-450 within the C-terminus are essential for agonist-induced hGLP-1R internalisation. In conclusion, these findings demonstrate the hGLP-1R has distinct regions within the C-terminal domain required for its cell surface expression, activity and agonist-induced internalisation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Mycobacterial secretion systems ESX-1 and ESX-5 play distinct roles in host cell death and inflammasome activation

    KAUST Repository

    Abdallah, Abdallah

    2011-09-28

    During infection of humans and animals, pathogenic mycobacteria manipulate the host cell causing severe diseases such as tuberculosis and leprosy. To understand the basis of mycobacterial pathogenicity, it is crucial to identify the molecular virulence mechanisms. In this study, we address the contribution of ESX-1 and ESX-5 - two homologous type VII secretion systems of mycobacteria that secrete distinct sets of immune modulators - during the macrophage infection cycle. Using wild-type, ESX-1- and ESX-5-deficient mycobacterial strains, we demonstrate that these secretion systems differentially affect subcellular localization and macrophage cell responses. We show that in contrast to ESX-1, the effector proteins secreted by ESX-5 are not required for the translocation of Mycobacterium tuberculosis or Mycobacterium marinum to the cytosol of host cells. However, the M. marinum ESX-5 mutant does not induce inflammasome activation and IL-1b activation. The ESX-5 system also induces a caspase-independent cell death after translocation has taken place. Importantly, by means of inhibitory agents and small interfering RNA experiments, we reveal that cathepsin B is involved in both the induction of cell death and inflammasome activation upon infection with wild-type mycobacteria. These results reveal distinct roles for two different type VII secretion systems during infection and shed light on how virulent mycobacteria manipulate the host cell in various ways to replicate and spread. Copyright © 2011 by The American Association of Immunologists, Inc.

  18. Distinct Temporal Coordination of Spontaneous Population Activity between Basal Forebrain and Auditory Cortex

    Directory of Open Access Journals (Sweden)

    Josue G. Yague

    2017-09-01

    Full Text Available The basal forebrain (BF has long been implicated in attention, learning and memory, and recent studies have established a causal relationship between artificial BF activation and arousal. However, neural ensemble dynamics in the BF still remains unclear. Here, recording neural population activity in the BF and comparing it with simultaneously recorded cortical population under both anesthetized and unanesthetized conditions, we investigate the difference in the structure of spontaneous population activity between the BF and the auditory cortex (AC in mice. The AC neuronal population show a skewed spike rate distribution, a higher proportion of short (≤80 ms inter-spike intervals (ISIs and a rich repertoire of rhythmic firing across frequencies. Although the distribution of spontaneous firing rate in the BF is also skewed, a proportion of short ISIs can be explained by a Poisson model at short time scales (≤20 ms and spike count correlations are lower compared to AC cells, with optogenetically identified cholinergic cell pairs showing exceptionally higher correlations. Furthermore, a smaller fraction of BF neurons shows spike-field entrainment across frequencies: a subset of BF neurons fire rhythmically at slow (≤6 Hz frequencies, with varied phase preferences to ongoing field potentials, in contrast to a consistent phase preference of AC populations. Firing of these slow rhythmic BF cells is correlated to a greater degree than other rhythmic BF cell pairs. Overall, the fundamental difference in the structure of population activity between the AC and BF is their temporal coordination, in particular their operational timescales. These results suggest that BF neurons slowly modulate downstream populations whereas cortical circuits transmit signals on multiple timescales. Thus, the characterization of the neural ensemble dynamics in the BF provides further insight into the neural mechanisms, by which brain states are regulated.

  19. Angiogenesis interactome and time course microarray data reveal the distinct activation patterns in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Liang-Hui Chu

    Full Text Available Angiogenesis involves stimulation of endothelial cells (EC by various cytokines and growth factors, but the signaling mechanisms are not completely understood. Combining dynamic gene expression time-course data for stimulated EC with protein-protein interactions associated with angiogenesis (the "angiome" could reveal how different stimuli result in different patterns of network activation and could implicate signaling intermediates as points for control or intervention. We constructed the protein-protein interaction networks of positive and negative regulation of angiogenesis comprising 367 and 245 proteins, respectively. We used five published gene expression datasets derived from in vitro assays using different types of blood endothelial cells stimulated by VEGFA (vascular endothelial growth factor A. We used the Short Time-series Expression Miner (STEM to identify significant temporal gene expression profiles. The statistically significant patterns between 2D fibronectin and 3D type I collagen substrates for telomerase-immortalized EC (TIME show that different substrates could influence the temporal gene activation patterns in the same cell line. We investigated the different activation patterns among 18 transmembrane tyrosine kinase receptors, and experimentally measured the protein level of the tyrosine-kinase receptors VEGFR1, VEGFR2 and VEGFR3 in human umbilical vein EC (HUVEC and human microvascular EC (MEC. The results show that VEGFR1-VEGFR2 levels are more closely coupled than VEGFR1-VEGFR3 or VEGFR2-VEGFR3 in HUVEC and MEC. This computational methodology can be extended to investigate other molecules or biological processes such as cell cycle.

  20. Distinct BOLD Activation Profiles Following Central and Peripheral Oxytocin Administration in Awake Rats.

    Science.gov (United States)

    Ferris, Craig F; Yee, Jason R; Kenkel, William M; Dumais, Kelly Marie; Moore, Kelsey; Veenema, Alexa H; Kulkarni, Praveen; Perkybile, Allison M; Carter, C Sue

    2015-01-01

    A growing body of literature has suggested that intranasal oxytocin (OT) or other systemic routes of administration can alter prosocial behavior, presumably by directly activating OT sensitive neural circuits in the brain. Yet there is no clear evidence that OT given peripherally can cross the blood-brain barrier at levels sufficient to engage the OT receptor. To address this issue we examined changes in blood oxygen level-dependent (BOLD) signal intensity in response to peripheral OT injections (0.1, 0.5, or 2.5 mg/kg) during functional magnetic resonance imaging (fMRI) in awake rats imaged at 7.0 T. These data were compared to OT (1 μg/5 μl) given directly to the brain via the lateral cerebroventricle. Using a 3D annotated MRI atlas of the rat brain segmented into 171 brain areas and computational analysis, we reconstructed the distributed integrated neural circuits identified with BOLD fMRI following central and peripheral OT. Both routes of administration caused significant changes in BOLD signal within the first 10 min of administration. As expected, central OT activated a majority of brain areas known to express a high density of OT receptors, e.g., lateral septum, subiculum, shell of the accumbens, bed nucleus of the stria terminalis. This profile of activation was not matched by peripheral OT. The change in BOLD signal to peripheral OT did not show any discernible dose-response. Interestingly, peripheral OT affected all subdivisions of the olfactory bulb, in addition to the cerebellum and several brainstem areas relevant to the autonomic nervous system, including the solitary tract nucleus. The results from this imaging study do not support a direct central action of peripheral OT on the brain. Instead, the patterns of brain activity suggest that peripheral OT may interact at the level of the olfactory bulb and through sensory afferents from the autonomic nervous system to influence brain activity.

  1. On the relation between 2D:4D and sex-dimorphic personality traits.

    Science.gov (United States)

    Hampson, Elizabeth; Ellis, Connie L; Tenk, Christine M

    2008-02-01

    Several personality traits, including aggressiveness and sensation seeking, have been hypothesized to be influenced by prenatal androgen exposure, though evidence for this proposition is limited. We investigated whether individual differences in aggressiveness, sensation seeking, and several prosocial personality traits can be predicted from differences in the 2D:4D digit ratio, a putative marker of prenatal androgen activity. A total of 164 undergraduates (87 men, 77 women) completed self-report measures of physical and verbal aggression, as well as a standardized measure of sensation seeking, and five scales to assess empathy, nurturance, expressivity/femininity, instrumentality/masculinity, and assertiveness. Two sex-dimorphic tests of spatial ability also were included. Men had a lower 2D:4D ratio than women, confirming the typical sex difference in digit proportions. Significant sex differences were observed on 10 of the 11 personality scales purported to show sex differences and on both tests of spatial ability. The 2D:4D ratio was a significant predictor of scores on three of the four aggression subscales, total aggression, thrill and adventure seeking, and total sensation-seeking, in the sample as a whole and in women. In men, correlations with 2D:4D were significant only for total sensation-seeking and verbal aggression. In both sexes, lower 2D:4D ratios were associated with increased aggressiveness and sensation seeking. For the spatial tests, there was no evidence of any association with 2D:4D in either men or women. The 2D:4D digit ratio may be a valid, though weak, predictor of selective sex-dependent traits that are sensitive to testosterone.

  2. Distinct Trypanosoma cruzi isolates induce activation and apoptosis of human neutrophils.

    Directory of Open Access Journals (Sweden)

    Luísa M D Magalhães

    Full Text Available Neutrophils are critical players in the first line of defense against pathogens and in the activation of subsequent cellular responses. We aimed to determine the effects of the interaction of Trypanosoma cruzi with human neutrophils, using isolates of the two major discrete type units (DTUs associated with Chagas' disease in Latin America (clone Col1.7G2 and Y strain, DTU I and II, respectively. Thus, we used CFSE-stained trypomastigotes to measure neutrophil-T. cruzi interaction, neutrophil activation, cytokine expression and death, after infection with Col1.7G2 and Y strain. Our results show that the frequency of CFSE+ neutrophils, indicative of interaction, and CFSE intensity on a cell-per-cell basis were similar when comparing Col1.7G2 and Y strains. Interaction with T. cruzi increased neutrophil activation, as measured by CD282, CD284, TNF and IL-12 expression, although at different levels between the two strains. No change in IL-10 expression was observed after interaction of neutrophils with either strain. We observed that exposure to Y and Col1.7G2 caused marked neutrophil death. This was specific to neutrophils, since interaction of either strain with monocytes did not cause death. Our further analysis showed that neutrophil death was a result of apoptosis, which was associated with an upregulation of TNF-receptor, TNF and FasLigand, but not of Fas. Induction of TNF-associated neutrophil apoptosis by the different T. cruzi isolates may act as an effective common mechanism to decrease the host's immune response and favor parasite survival.

  3. Conformational Rigidity and Protein Dynamics at Distinct Timescales Regulate PTP1B Activity and Allostery.

    Science.gov (United States)

    Choy, Meng S; Li, Yang; Machado, Luciana E S F; Kunze, Micha B A; Connors, Christopher R; Wei, Xingyu; Lindorff-Larsen, Kresten; Page, Rebecca; Peti, Wolfgang

    2017-02-16

    Protein function originates from a cooperation of structural rigidity, dynamics at different timescales, and allostery. However, how these three pillars of protein function are integrated is still only poorly understood. Here we show how these pillars are connected in Protein Tyrosine Phosphatase 1B (PTP1B), a drug target for diabetes and cancer that catalyzes the dephosphorylation of numerous substrates in essential signaling pathways. By combining new experimental and computational data on WT-PTP1B and ≥10 PTP1B variants in multiple states, we discovered a fundamental and evolutionarily conserved CH/π switch that is critical for positioning the catalytically important WPD loop. Furthermore, our data show that PTP1B uses conformational and dynamic allostery to regulate its activity. This shows that both conformational rigidity and dynamics are essential for controlling protein activity. This connection between rigidity and dynamics at different timescales is likely a hallmark of all enzyme function. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Yam storage protein dioscorins from Dioscorea alata and Dioscorea japonica exhibit distinct immunomodulatory activities in mice.

    Science.gov (United States)

    Lin, Pei-Lan; Lin, Kuo-Wei; Weng, Ching-Feng; Lin, Kuo-Chih

    2009-06-10

    The aim of this study was to elucidate the effect of the major storage protein dioscorin isolated from two different yam species, Tainong No. 1 (TN1-dioscorins) and Japanese yam (Dj-dioscorins), on the immune activities of mice. Dj-dioscorins, like TN1-dioscorins, could induce expression of the pro-inflammatory cytokines and stimulate phagocytosis of RAW 264.7. Intraperitoneal injection of the TN1-dioscorins into mice stimulated phagocytosis of bone marrow, spleen, and thymic cells. In contrast, the T and B cells in bone marrow, spleen, and thymus isolated from mice injected with Dj-dioscorins had higher proliferative responses to mitogens. Furthermore, Dj-dioscorins enhanced proliferation of CD4(+), CD8(+), and Tim3(+) (Th1) cells in spleen and CD19(+) cells in both spleen and thymus. Supplement of Dj-dioscorins in the lymphoid cells isolated from Dj-dioscorins primed mice induced cell proliferation of both spleen and thymic cells. These findings indicated that TN1-dioscorins have a higher ability to stimulate the phagocytic activity of the lymphoid cells than Dj-dioscorins, whereas Dj-dioscorins possess more abilities than TN1-dioscorins to enhance the proliferation of the lymphoid cells.

  5. Distinct structural features of TFAM drive mitochondrial DNA packaging versus transcriptional activation.

    Science.gov (United States)

    Ngo, Huu B; Lovely, Geoffrey A; Phillips, Rob; Chan, David C

    2014-01-01

    TFAM (transcription factor A, mitochondrial) is a DNA-binding protein that activates transcription at the two major promoters of mitochondrial DNA (mtDNA)--the light strand promoter (LSP) and the heavy strand promoter 1 (HSP1). Equally important, it coats and packages the mitochondrial genome. TFAM has been shown to impose a U-turn on LSP DNA; however, whether this distortion is relevant at other sites is unknown. Here we present crystal structures of TFAM bound to HSP1 and to nonspecific DNA. In both, TFAM similarly distorts the DNA into a U-turn. Yet, TFAM binds to HSP1 in the opposite orientation from LSP explaining why transcription from LSP requires DNA bending, whereas transcription at HSP1 does not. Moreover, the crystal structures reveal dimerization of DNA-bound TFAM. This dimerization is dispensable for DNA bending and transcriptional activation but is important in DNA compaction. We propose that TFAM dimerization enhances mitochondrial DNA compaction by promoting looping of the DNA.

  6. Role of dopamine D4 receptors in copulatory behavior: Studies with selective D4 agonists and antagonists in male rats.

    Science.gov (United States)

    Sanna, Fabrizio; Contini, Andrea; Melis, Maria Rosaria; Argiolas, Antonio

    2015-10-01

    Dopamine influences the anticipatory and consummatory phases of sexual behavior, by acting on receptors of the D2 family (D2, D3 and D4) and in particular of the D2 subtype, although evidence for a role of D4 receptors in erectile function and copulatory behavior is also available. In order to clarify such a role of D4 receptors, the effect of selective D4 receptor agonists and antagonists on copulatory behavior of sexually potent male rats in classic copulation tests with a receptive female, was compared with that of apomorphine and haloperidol, a classic dopamine receptor agonist and antagonist, respectively. PD-168,077 (0.05-0.2mg/kg) and ABT-724 (0.01-0.04mg/kg), two selective D4 receptor agonists, given subcutaneously, improved dose-dependently copulatory behavior as shown by the decrease of mount frequency and post ejaculatory interval induced by PD-168,077, and of mount frequency, ejaculation latency, post ejaculatory and inter intromission intervals induced by ABT-724, and by the increase of ejaculation frequency and copulatory efficacy induced by both drugs. Conversely, L-745,870 (1-5mg/kg), a selective D4 receptor antagonist, given intraperitoneally, impaired dose-dependently copulatory behavior, as shown by the increase in intromission and ejaculation latencies, mount frequency, post ejaculatory interval and the decrease in ejaculation frequency and copulatory efficacy induced by this drug. L-745,870 (5mg/kg) administered before PD-168,077 (0.2mg/kg) or ABT-724 (0.04mg/kg), also abolished completely the facilitatory effects of both PD-168,077 and ABT-724 on sexual behavior. These results confirm the involvement of D4 receptors in specific aspects of male rat copulatory behavior that overlap only partially with those influenced by apomorphine and haloperidol. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Mood Dimensions Show Distinct Within-Subject Associations With Non-exercise Activity in Adolescents: An Ambulatory Assessment Study

    Directory of Open Access Journals (Sweden)

    Elena D. Koch

    2018-03-01

    . Specifically, adolescents who felt more content, full of energy, or less calm were more physically active in subsequent timeframes. Overall, our results demonstrate significant associations of mood with non-exercise activity in younger ages and converge with the previously observed association between mood and physical activity in adults. This knowledge on distinct associations of mood-dimensions with non-exercise activity may help to foster physical activity levels in adolescents.

  8. Two structurally distinct chalcone dimers from Helichrysum zivojinii and their activities in cancer cell lines.

    Science.gov (United States)

    Aljančić, Ivana S; Vučković, Ivan; Jadranin, Milka; Pešić, Milica; Dorđević, Iris; Podolski-Renić, Ana; Stojković, Sonja; Menković, Nebojša; Vajs, Vlatka E; Milosavljević, Slobodan M

    2014-02-01

    Dimers tomoroside A (1) and tomoroside B (2) of the co-occuring known chalcone monomer (3), along with the seven known flavonoid glucosides (4-10), were isolated from the aerial parts of Helichrysum zivojinii Černjavski & Soška. The structures of the isolated compounds were elucidated by spectroscopic techniques. Compound 1 inhibited topo IIα and hif-1α expression and stimulated doxorubicin anticancer effect, while 2 increased the expression of hif-1α, probably acting as antioxidant and redox status modulator. Notably, 2 synergized with Tipifarnib showing potential to improve the action of this new chemotherapeutic involved in the modulation of mitogene activated protein (MAP) kinase signaling pathway. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Using 2D: 4D digit ratios to determine motor skills in children.

    Science.gov (United States)

    Wang, Y; Wang, H-L; Li, Y-H; Zhu, F-L; Li, S-J; Ni, H

    2016-03-01

    In past few decades, there has an outburst of research surrounding second to fourth finger digit ratio (2D:4D) and its relation to prenatal sex steroids including both testosterone and estrogen. In utero, testosterone and estrogen are responsible for the differences in digit ratio between the genders. Recent research has tried to extend past the influence of steroids and look at the potential effect of digit ratios on fine and gross motor skills in children. We compiled the current understanding of the connection between sex hormones and the development of the 2D:4D ratio as well as the effect the ratio has on motor skills. There seems to be a significant positive correlation between 2D:4D digit ratio and precision of fine motor skill. In addition, there is a negative correlation between 2D:4D ratio and speed of fine motor activity. In this review, we will outline the use of 2D:4D ratio as a biomarker for prenatal sex steroids and through that, a proxy marker for fine and gross motor skills.

  10. Neural substrates of semantic relationships: common and distinct left-frontal activities for generation of synonyms vs. antonyms.

    Science.gov (United States)

    Jeon, Hyeon-Ae; Lee, Kyoung-Min; Kim, Young-Bo; Cho, Zang-Hee

    2009-11-01

    Synonymous and antonymous relationships among words may reflect the organization and/or processing in the mental lexicon and its implementation in the brain. In this study, functional magnetic resonance imaging (fMRI) is employed to compare brain activities during generation of synonyms (SYN) and antonyms (ANT) prompted by the same words. Both SYN and ANT, when compared with reading nonwords (NW), activated a region in the left middle frontal gyrus (BA 46). Neighboring this region, there was a dissociation observed in that the ANT activation extended more anteriorly and laterally to the SYN activation. The activations in the left middle frontal gyrus may be related to mental processes that are shared in the SYN and ANT generations, such as engaging semantically related parts of mental lexicon for the word search, whereas the distinct activations unique for either SYN or ANT generation may reflect the additional component of antonym retrieval, namely, reversing the polarity of semantic relationship in one crucial dimension. These findings suggest that specific components in the semantic processing, such as the polarity reversal for antonym generation and the similarity assessment for synonyms, are separately and systematically laid out in the left-frontal cortex.

  11. Thionin-D4E1 chimeric protein protects plants against bacterial infections

    Science.gov (United States)

    Stover, Eddie W; Gupta, Goutam; Hao, Guixia

    2017-08-08

    The generation of a chimeric protein containing a first domain encoding either a pro-thionon or thionin, a second domain encoding D4E1 or pro-D4E1, and a third domain encoding a peptide linker located between the first domain and second domain is described. Either the first domain or the second domain is located at the amino terminal of the chimeric protein and the other domain (second domain or first domain, respectively) is located at the carboxyl terminal. The chimeric protein has antibacterial activity. Genetically altered plants and their progeny expressing a polynucleotide encoding the chimeric protein resist diseases caused by bacteria.

  12. Digit Ratio (2D:4D): A Biomarker for Prenatal Sex Steroids and Adult Sex Steroids in Challenge Situations.

    Science.gov (United States)

    Manning, John; Kilduff, Liam; Cook, Christian; Crewther, Blair; Fink, Bernhard

    2014-01-01

    Digit ratio (2D:4D) denotes the relative length of the second and fourth digits. This ratio is considered to be a biomarker of the balance between fetal testosterone (T) and estrogen (E) in a narrow window of early ontogeny. Evidence for this assertion is derived from direct and indirect measures of prenatal hormonal exposure (in experimental animals, via amniotic fluid samples and in the study of sex-typical traits) in relation to 2D:4D. In contrast, the relationships between 2D:4D and levels of sex steroids in adults are less clear, as many correlational studies of 2D:4D and adult sex steroids have concluded that this association is statistically non-significant. Here, we suggest that in order to understand the link between 2D:4D and sex hormones, one must consider both fetal organizing and adult activating effects of T and E. In particular, we hypothesize that 2D:4D correlates with organizing effects on the endocrine system that moderate activating effects in adulthood. We argue that this is particularly evident in "challenging" conditions such as aggressive and sexual encounters, in which individuals show increased levels of T. We discuss this refinement of the 2D:4D paradigm in relation to the links between 2D:4D and sports performance, and aggression.

  13. Analysis of tube vibrations in D-4 steam generator

    International Nuclear Information System (INIS)

    Mavko, B.; Peterlin, G.; Boltezar, M.

    1983-01-01

    Accelerometer data for the most exposed tube in steam generator D-4 were recorded on magnetic tape. Procedures for calculations of the most characteristic parameters were prepared for spectral analyzer on SD 360. Parameters which most satisfactorily describe the vibrations are power spectral densities peak to peak acceleration volume and root mean square displacement. Computer program was written to calculate the natural frequencies of a multispaned tube. Procedures and the computer program will be used for independent analysis of tube vibrations in Krsko D-4 type steam generator. (author)

  14. Higher point spin field correlators in D=4 superstring theory

    International Nuclear Information System (INIS)

    Haertl, D.; Schlotterer, O.; Stieberger, S.

    2010-01-01

    Calculational tools are provided allowing to determine general tree-level scattering amplitudes for processes involving bosons and fermions in heterotic and superstring theories in four space-time dimensions. We compute higher-point superstring correlators involving massless four-dimensional fermionic and spin fields. In D=4 these correlators boil down to a product of two pure spin field correlators of left- and right-handed spin fields. This observation greatly simplifies the computation of such correlators. The latter are basic ingredients to compute multi-fermion superstring amplitudes in D=4. Their underlying fermionic structure and the fermionic couplings in the effective action are determined by these correlators.

  15. Distinct radioprotective activities of major heat shock proteins in irradiated mammalian cells

    International Nuclear Information System (INIS)

    Kabakov, Alexander; Malyutina, Yana; Kudryavtsev, Vladimir

    2008-01-01

    Full text: Several years ago we have suggested that heat shock proteins (Hsps) can be involved in cellular and tissue mechanisms of protection from ionizing radiation. At present, the accumulated experimental data do allow us to characterize three major mammalian Hsps, Hsp70, Hsp27 and Hsp90, as specific endogenous radioprotectors which are able to prevent or minimize cell death resulting from the radiation exposure. It follows from the many findings that the radioprotective effect of these Hsps is particularly manifested in their ability to attenuate apoptosis in various normal and tumor cells irradiated in vivo or in vitro. The obtained data already enable to suggest three main mechanisms of the radioprotection conferred by the excess Hsps: 1) Modulation of the intracellular signaling so that the apoptotic signal transduction is blocked, whereas the 'cell survival' signal transduction is stimulated; 2) Suppression of the radiation-associated free radical generation and apoptosis induced by reactive oxygen species (ROS); 3) Attenuation of the genotoxic impact of ionizing radiation. The latter suggested mechanism seems particularly intriguing and implies that the excess Hsps can somehow contribute to protection/repair of genomic DNA from radiation-induced damage. According to our recent results, Hsp90 is indeed involved in the post-irradiation repair of nuclear DNA, while excess Hsp70 can beneficially affect the p53-mediated DNA damage response in irradiated cells to ensure their long-term survival and recovery. As for Hsp27, we found that its accumulation in target cells increases their radioresistance by enhancing the irradiation-responsive activation of anti apoptotic pathways. While the Hsp70 and Hsp27 seem to perform different functions in irradiated cells, the synergistic enhancement of radioprotection was clearly observed in the cells enriched by the both the Hsps. In vivo, such radioprotective activities of the major mammalian Hsps may play a role in

  16. A Rationally Designed Histone Deacetylase Inhibitor with Distinct Antitumor Activity against Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Ya-Ting Yang

    2009-06-01

    Full Text Available Histone deacetylase inhibitors (HDACIs are a class of antineoplastic agents previously demonstrating preclinical chemosensitizing activity against drug-resistant cancer cells and mouse xenografts. However, whereas clinical studies have shown efficacy against human hematologic malignancies, solid tumor trials have proved disappointing. We previously developed a novel HDACI, “OSU-HDAC42,” and herein examine its activity against ovarian cancer cell lines and xenografts. OSU-HDAC42, (i unlike most HDACIs, elicited a more than five-fold increase in G2-phase cells, at 2.5 µM, with G2 arrest followed by apoptosis; (ii at 1.0 µM, completely repressed messenger RNA expression of the cell cycle progression gene cdc2; (iii at low doses (0.25–1.0 µM for 24 hours, induced tumor cell epithelial differentiation, as evidenced by morphology changes and a more than five-fold up-regulation of epithelium-specific cytokeratins; (iv potently abrogated the growth of numerous ovarian cancer cells, with IC50 values of 0.5 to 1.0 µM, whereas also remaining eight-fold less toxic (IC50 of 8.6 µM to normal ovarian surface epithelial cells; and (v chemosensitizated platinum-resistant mouse xenografts to cisplatin. Compared with the clinically approved HDACI suberoylanilide hydroxamic acid (vorinostat, 1.0 µM OSU-HDAC42 was more biochemically potent (i.e., enzyme-inhibitory, as suggested by greater gene up-regulation and acetylation of both histone and nonhistone proteins. In p53-dysfunctional cells, however, OSU-HDAC42 was two- to eight-fold less inductive of p53-regulated genes, whereas also having a two-fold higher IC50 than p53-functional cells, demonstrating some interaction with p53 tumor-suppressive cascades. These findings establish OSU-HDAC42 as a promising therapeutic agent for drug-resistant ovarian cancer and justify its further investigation.

  17. Imaging Surrogates of Disease Activity in Neuromyelitis Optica Allow Distinction from Multiple Sclerosis.

    Science.gov (United States)

    Matthews, Lucy; Kolind, Shannon; Brazier, Alix; Leite, Maria Isabel; Brooks, Jonathan; Traboulsee, Anthony; Jenkinson, Mark; Johansen-Berg, Heidi; Palace, Jacqueline

    2015-01-01

    Inflammatory demyelinating lesions of the central nervous system are a common feature of both neuromyelitis optica and multiple sclerosis. Despite this similarity, it is evident clinically that the accumulation of disability in patients with neuromyelitis optica is relapse related and that a progressive phase is very uncommon. This poses the question whether there is any pathological evidence of disease activity or neurodegeneration in neuromyelitis optica between relapses. To investigate this we conducted a longitudinal advanced MRI study of the brain and spinal cord in neuromyelitis optica patients, comparing to patients with multiple sclerosis and controls. We found both cross-sectional and longitudinal evidence of diffusely distributed neurodegenerative surrogates in the multiple sclerosis group (including thalamic atrophy, cervical cord atrophy and progressive widespread diffusion and myelin water imaging abnormalities in the normal appearing white matter) but not in those with neuromyelitis optica, where localised abnormalities in the optic radiations of those with severe visual impairment were noted. In addition, between relapses, there were no new silent brain lesions in the neuromyelitis optica group. These findings indicate that global central nervous system neurodegeneration is not a feature of neuromyelitis optica. The work also questions the theory that neurodegeneration in multiple sclerosis is a chronic sequela to prior inflammatory and demyelinating pathology, as this has not been found to be the case in neuromyelitis optica where the lesions are often more destructive.

  18. Imaging Surrogates of Disease Activity in Neuromyelitis Optica Allow Distinction from Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Lucy Matthews

    Full Text Available Inflammatory demyelinating lesions of the central nervous system are a common feature of both neuromyelitis optica and multiple sclerosis. Despite this similarity, it is evident clinically that the accumulation of disability in patients with neuromyelitis optica is relapse related and that a progressive phase is very uncommon. This poses the question whether there is any pathological evidence of disease activity or neurodegeneration in neuromyelitis optica between relapses. To investigate this we conducted a longitudinal advanced MRI study of the brain and spinal cord in neuromyelitis optica patients, comparing to patients with multiple sclerosis and controls. We found both cross-sectional and longitudinal evidence of diffusely distributed neurodegenerative surrogates in the multiple sclerosis group (including thalamic atrophy, cervical cord atrophy and progressive widespread diffusion and myelin water imaging abnormalities in the normal appearing white matter but not in those with neuromyelitis optica, where localised abnormalities in the optic radiations of those with severe visual impairment were noted. In addition, between relapses, there were no new silent brain lesions in the neuromyelitis optica group. These findings indicate that global central nervous system neurodegeneration is not a feature of neuromyelitis optica. The work also questions the theory that neurodegeneration in multiple sclerosis is a chronic sequela to prior inflammatory and demyelinating pathology, as this has not been found to be the case in neuromyelitis optica where the lesions are often more destructive.

  19. Endothelial juxtaposition of distinct adult stem cells activates angiogenesis signaling molecules in endothelial cells.

    Science.gov (United States)

    Mohammadi, Elham; Nassiri, Seyed Mahdi; Rahbarghazi, Reza; Siavashi, Vahid; Araghi, Atefeh

    2015-12-01

    Efficacy of therapeutic angiogenesis needs a comprehensive understanding of endothelial cell (EC) function and biological factors and cells that interplay with ECs. Stem cells are considered the key components of pro- and anti-angiogenic milieu in a wide variety of physiopathological states, and interactions of EC-stem cells have been the subject of controversy in recent years. In this study, the potential effects of three tissue-specific adult stem cells, namely rat marrow-derived mesenchymal stem cells (rBMSCs), rat adipose-derived stem cells (rADSCs) and rat muscle-derived satellite cells (rSCs), on the endothelial activation of key angiogenic signaling molecules, including VEGF, Ang-2, VEGFR-2, Tie-2, and Tie2-pho, were investigated. Human umbilical vein endothelial cells (HUVECs) and rat lung microvascular endothelial cells (RLMECs) were cocultured with the stem cells or incubated with the stem cell-derived conditioned media on Matrigel. Following HUVEC-stem cell coculture, CD31-positive ECs were flow sorted and subjected to western blotting to analyze potential changes in the expression of the pro-angiogenic signaling molecules. Elongation and co-alignment of the stem cells were seen along the EC tubes in the EC-stem cell cocultures on Matrigel, with cell-to-cell dye communication in the EC-rBMSC cocultures. Moreover, rBMSCs and rADSCs significantly improved endothelial tubulogenesis in both juxtacrine and paracrine manners. These two latter stem cells dynamically up-regulated VEGF, Ang-2, VREGR-2, and Tie-2 but down-regulated Tie2-pho and the Tie2-pho/Tie-2 ratio in HUVECs. Induction of pro-angiogenic signaling in ECs by marrow- and adipose-derived MSCs further indicates the significance of stem cell milieu in angiogenesis dynamics.

  20. Hypoxia-Inducible Factor 3 Is an Oxygen-Dependent Transcription Activator and Regulates a Distinct Transcriptional Response to Hypoxia

    Directory of Open Access Journals (Sweden)

    Peng Zhang

    2014-03-01

    Full Text Available Hypoxia-inducible factors (HIFs play key roles in the cellular response to hypoxia. It is widely accepted that whereas HIF-1 and HIF-2 function as transcriptional activators, HIF-3 inhibits HIF-1/2α action. Contrary to this idea, we show that zebrafish Hif-3α has strong transactivation activity. Hif-3α is degraded under normoxia. Mutation of P393, P493, and L503 inhibits this oxygen-dependent degradation. Transcriptomics and chromatin immunoprecipitation analyses identify genes that are regulated by Hif-3α, Hif-1α, or both. Under hypoxia or when overexpressed, Hif-3α binds to its target gene promoters and upregulates their expression. Dominant-negative inhibition and knockdown of Hif-3α abolish hypoxia-induced Hif-3α-promoter binding and gene expression. Hif-3α not only mediates hypoxia-induced growth and developmental retardation but also possesses hypoxia-independent activities. Importantly, transactivation activity is conserved and human HIF-3α upregulates similar genes in human cells. These findings suggest that Hif-3 is an oxygen-dependent transcription factor and activates a distinct transcriptional response to hypoxia.

  1. Distinct iEEG activity patterns in temporal-limbic and prefrontal sites induced by emotional intentionality.

    Science.gov (United States)

    Singer, Neomi; Podlipsky, Ilana; Esposito, Fabrizio; Okon-Singer, Hadas; Andelman, Fani; Kipervasser, Svetlana; Neufeld, Miri Y; Goebel, Rainer; Fried, Itzhak; Hendler, Talma

    2014-11-01

    Our emotions tend to be directed towards someone or something. Such emotional intentionality calls for the integration between two streams of information; abstract hedonic value and its associated concrete content. In a previous functional magnetic resonance imaging (fMRI) study we found that the combination of these two streams, as modeled by short emotional music excerpts and neutral film clips, was associated with synergistic activation in both temporal-limbic (TL) and ventral-lateral PFC (vLPFC) regions. This additive effect implies the integration of domain-specific 'affective' and 'cognitive' processes. Yet, the low temporal resolution of the fMRI limits the characterization of such cross-domain integration. To this end, we complemented the fMRI data with intracranial electroencephalogram (iEEG) recordings from twelve patients with intractable epilepsy. As expected, the additive fMRI activation in the amygdala and vLPFC was associated with distinct spatio-temporal iEEG patterns among electrodes situated within the vicinity of the fMRI activation foci. On the one hand, TL channels exhibited a transient (0-500 msec) increase in gamma power (61-69 Hz), possibly reflecting initial relevance detection or hedonic value tagging. On the other hand, vLPFC channels showed sustained (1-12 sec) suppression of low frequency power (2.3-24 Hz), possibly mediating changes in gating, enabling an on-going readiness for content-based processing of emotionally tagged signals. Moreover, an additive effect in delta-gamma phase-amplitude coupling (PAC) was found among the TL channels, possibly reflecting the integration between distinct domain specific processes. Together, this study provides a multi-faceted neurophysiological signature for computations that possibly underlie emotional intentionality in humans. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Trigonal bipyramidal 5d-4f molecules with SMM behavior.

    Science.gov (United States)

    Saber, Mohamed R; Dunbar, Kim R

    2014-02-28

    A family of trigonal bipyramidal (TBP) 5d-4f cyanide bridged aggregates were synthesized that exhibit slow relaxation of the magnetization below 4 K as indicated by a signal in the out-of-phase ac susceptibility data under zero field.

  3. Gauge and gravitational anomalies in D=4 N=1 orientifolds.

    NARCIS (Netherlands)

    S Scrucca, C.; Serone, M.

    1999-01-01

    We analyze in detail the cancellation of U(1)-gauge and U(1)-gravitational anomalies in certain D=4 N=1 Type IIB orientifolds, from a string theory point of view. We verify the proposal that these anomalies are cancelled by a Green-Schwarz mechanism involving only twisted RR fields.By factorizing

  4. The T-cell-specific adapter protein family: TSAd, ALX, and SH2D4A/SH2D4B.

    Science.gov (United States)

    Lapinski, Philip E; Oliver, Jennifer A; Bodie, Jennifer N; Marti, Francesc; King, Philip D

    2009-11-01

    Adapter proteins play key roles in intracellular signal transduction through complex formation with catalytically active signaling molecules. In T lymphocytes, the role of several different types of adapter proteins in T-cell antigen receptor signal transduction is well established. An exception to this is the family of T-cell-specific adapter (TSAd) proteins comprising of TSAd, adapter protein of unknown function (ALX), SH2D4A, and SH2D4B. Only recently has the function of these adapters in T-cell signal transduction been explored. Here, we discuss advances in our understanding of the role of this family of adapter proteins in T cells. Their function as regulators of signal transduction in other cell types is also discussed.

  5. Conformational Activation of Argonaute by Distinct yet Coordinated Actions of the Hsp70 and Hsp90 Chaperone Systems.

    Science.gov (United States)

    Tsuboyama, Kotaro; Tadakuma, Hisashi; Tomari, Yukihide

    2018-05-17

    Loading of small RNAs into Argonaute, the core protein in RNA silencing, requires the Hsp70/Hsp90 chaperone machinery. This machinery also activates many other clients, including steroid hormone receptors and kinases, but how their structures change during chaperone-dependent activation remains unclear. Here, we utilized single-molecule Förster resonance energy transfer (smFRET) to probe the conformational changes of Drosophila Ago2 mediated by the chaperone machinery. We found that empty Ago2 exists in various closed conformations. The Hsp70 system (Hsp40 and Hsp70) and the Hsp90 system (Hop, Hsp90, and p23) together render Ago2 into an open, active form. The Hsp70 system, but not the Hsp90 system alone, is sufficient for Ago2 to partially populate the open form. Instead, the Hsp90 system is required to extend the dwell time of Ago2 in the open state, which must be transiently primed by the Hsp70 system. Our data uncover distinct and coordinated actions of the chaperone machinery, where the Hsp70 system expands the structural ensembles of Ago2 and the Hsp90 system captures and stabilizes the active form. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Assembly of the Arp5 (Actin-related Protein) Subunit Involved in Distinct INO80 Chromatin Remodeling Activities*

    Science.gov (United States)

    Yao, Wei; Beckwith, Sean L.; Zheng, Tina; Young, Thomas; Dinh, Van T.; Ranjan, Anand; Morrison, Ashby J.

    2015-01-01

    ATP-dependent chromatin remodeling, which repositions and restructures nucleosomes, is essential to all DNA-templated processes. The INO80 chromatin remodeling complex is an evolutionarily conserved complex involved in diverse cellular processes, including transcription, DNA repair, and replication. The functional diversity of the INO80 complex can, in part, be attributed to specialized activities of distinct subunits that compose the complex. Furthermore, structural analyses have identified biochemically discrete subunit modules that assemble along the Ino80 ATPase scaffold. Of particular interest is the Saccharomyces cerevisiae Arp5-Ies6 module located proximal to the Ino80 ATPase and the Rvb1-Rvb2 helicase module needed for INO80-mediated in vitro activity. In this study we demonstrate that the previously uncharacterized Ies2 subunit is required for Arp5-Ies6 association with the catalytic components of the INO80 complex. In addition, Arp5-Ies6 module assembly with the INO80 complex is dependent on distinct conserved domains within Arp5, Ies6, and Ino80, including the spacer region within the Ino80 ATPase domain. Arp5-Ies6 interacts with chromatin via assembly with the INO80 complex, as IES2 and INO80 deletion results in loss of Arp5-Ies6 chromatin association. Interestingly, ectopic addition of the wild-type Arp5-Ies6 module stimulates INO80-mediated ATP hydrolysis and nucleosome sliding in vitro. However, the addition of mutant Arp5 lacking unique insertion domains facilitates ATP hydrolysis in the absence of nucleosome sliding. Collectively, these results define the requirements of Arp5-Ies6 assembly, which are needed to couple ATP hydrolysis to productive nucleosome movement. PMID:26306040

  7. μ-τ symmetry and charged lepton mass hierarchy in a supersymmetric D4 model

    International Nuclear Information System (INIS)

    Hagedorn, C.; Ziegler, R.

    2010-01-01

    In this paper we discuss a supersymmetric D 4 xZ 5 model which leads to vanishing reactor mixing angle θ 13 =0 and maximal atmospheric mixing θ 23 =π/4 in the lepton sector at leading order, due to the preservation of nontrivial distinct D 4 subgroups in the charged lepton and neutrino sectors, respectively. The solar mixing angle θ 12 remains undetermined and is expected to be of order one. Since right-handed charged leptons transform as singlets under D 4 , the charged lepton mass hierarchy can be naturally accounted for. The model predicts inverted mass hierarchy for neutrinos. Additionally, we show that, unlike in most of the other models of this type, all vacuum expectation values of gauge singlets (flavons) can be determined through mass parameters of the superpotential. Next-to-leading order corrections to lepton masses and mixings are calculated and shown to be under control; in particular, the corrections to θ 23 =π/4 and θ 13 =0 are of the order of the generic expansion parameter ε≅0.04 and arise dominantly from the charged lepton sector.

  8. Lipid-laden cells differentially distributed in the aging brain are functionally active and correspond to distinct phenotypes.

    Science.gov (United States)

    Shimabukuro, Marilia Kimie; Langhi, Larissa Gutman Paranhos; Cordeiro, Ingrid; Brito, José M; Batista, Claudia Maria de Castro; Mattson, Mark P; Mello Coelho, Valeria de

    2016-03-31

    We characterized cerebral Oil Red O-positive lipid-laden cells (LLC) of aging mice evaluating their distribution, morphology, density, functional activities and inflammatory phenotype. We identified LLC in meningeal, cortical and neurogenic brain regions. The density of cerebral LLC increased with age. LLC presenting small lipid droplets were visualized adjacent to blood vessels or deeper in the brain cortical and striatal parenchyma of aging mice. LLC with larger droplets were asymmetrically distributed in the cerebral ventricle walls, mainly located in the lateral wall. We also found that LLC in the subventricular region co-expressed beclin-1 or LC3, markers for autophagosome or autophagolysosome formation, and perilipin (PLIN), a lipid droplet-associated protein, suggesting lipophagic activity. Some cerebral LLC exhibited β galactosidase activity indicating a senescence phenotype. Moreover, we detected production of the pro-inflammatory cytokine TNF-α in cortical PLIN(+) LLC. Some cortical NeuN(+) neurons, GFAP(+) glia limitans astrocytes, Iba-1(+) microglia and S100β(+) ependymal cells expressed PLIN in the aging brain. Our findings suggest that cerebral LLC exhibit distinct cellular phenotypes and may participate in the age-associated neuroinflammatory processes.

  9. Nonspecific activation of murine lymphocytes. IV. Proliferation of a distinct, late maturing lymphocyte subpopulation induced by 2-mercaptoethanol

    International Nuclear Information System (INIS)

    Goodman, M.G.; Fidler, J.M.; Weigle, W.O.

    1978-01-01

    The lymphocyte subpopulations that are activated by 2-ME, LPS, poly IC, and PPD were studied in terms of their maturational characteristics. Attempts to stimulate hepatic and splenic lymphoid cells from mice of different ages with these mitogens demonstrated a well ordered sequence for the emergency of mitogen responsiveness in C3H mice: reactivity to LPS and Poly IC was observed early in maturation and was followed by that to PPD, and finally by the development of responsiveness to 2-ME. The same sequence appeared when the mitogen responsiveness of lethally irradiated, fetal liver-reconstituted syngeneic adult recipients was examined. The mitogenic action of 2-ME was dissociated from its ability to enhance lymphocyte reactivity to other mitogens in mice too young to respond to 2-ME as a mitogen. Experiments in which additivity of responses was assayed by adding mitogens to culture singly or conjointly indicated that LPS and Poly IC activate nearly identical B lymphocyte subpopulations, whereas PPD stimulates a subset of cells distinct from that which is responsive to the former two mitogens. The mitogen responsiveness of CBA/N mice, relative to normal CBA/WEHI mice, was shown to decrease as a function of the maturity of the subpopulation of lymphocytes activated. The CBA/N mouse was shown to be unresponsive to stimulation by 2-ME

  10. Lipid-laden cells differentially distributed in the aging brain are functionally active and correspond to distinct phenotypes

    Science.gov (United States)

    Shimabukuro, Marilia Kimie; Langhi, Larissa Gutman Paranhos; Cordeiro, Ingrid; Brito, José M.; Batista, Claudia Maria de Castro; Mattson, Mark P.; de Mello Coelho, Valeria

    2016-01-01

    We characterized cerebral Oil Red O-positive lipid-laden cells (LLC) of aging mice evaluating their distribution, morphology, density, functional activities and inflammatory phenotype. We identified LLC in meningeal, cortical and neurogenic brain regions. The density of cerebral LLC increased with age. LLC presenting small lipid droplets were visualized adjacent to blood vessels or deeper in the brain cortical and striatal parenchyma of aging mice. LLC with larger droplets were asymmetrically distributed in the cerebral ventricle walls, mainly located in the lateral wall. We also found that LLC in the subventricular region co-expressed beclin-1 or LC3, markers for autophagosome or autophagolysosome formation, and perilipin (PLIN), a lipid droplet-associated protein, suggesting lipophagic activity. Some cerebral LLC exhibited β galactosidase activity indicating a senescence phenotype. Moreover, we detected production of the pro-inflammatory cytokine TNF-α in cortical PLIN+ LLC. Some cortical NeuN+ neurons, GFAP+ glia limitans astrocytes, Iba-1+ microglia and S100β+ ependymal cells expressed PLIN in the aging brain. Our findings suggest that cerebral LLC exhibit distinct cellular phenotypes and may participate in the age-associated neuroinflammatory processes. PMID:27029648

  11. Distinct licensing of IL-18 and IL-1β secretion in response to NLRP3 inflammasome activation.

    Directory of Open Access Journals (Sweden)

    Rebecca L Schmidt

    Full Text Available Inflammasome activation permits processing of interleukins (IL-1β and 18 and elicits cell death (pyroptosis. Whether these responses are independently licensed or are "hard-wired" consequences of caspase-1 (casp1 activity has not been clear. Here, we show that that each of these responses is independently regulated following activation of NLRP3 inflammasomes by a "non-canonical" stimulus, the secreted Listeria monocytogenes (Lm p60 protein. Primed murine dendritic cells (DCs responded to p60 stimulation with reactive oxygen species (ROS production and secretion of IL-1β and IL-18 but not pyroptosis. Inhibitors of ROS production inhibited secretion of IL-1β, but did not impair IL-18 secretion. Furthermore, DCs from caspase-11 (casp11-deficient 129S6 mice failed to secrete IL-1β in response to p60 but were fully responsive for IL-18 secretion. These findings reveal that there are distinct licensing requirements for processing of IL-18 versus IL-1β by NLRP3 inflammasomes.

  12. Dynamic Recruitment of Functionally Distinct Swi/Snf Chromatin Remodeling Complexes Modulates Pdx1 Activity in Islet β Cells

    Directory of Open Access Journals (Sweden)

    Brian McKenna

    2015-03-01

    Full Text Available Pdx1 is a transcription factor of fundamental importance to pancreas formation and adult islet β cell function. However, little is known about the positive- and negative-acting coregulators recruited to mediate transcriptional control. Here, we isolated numerous Pdx1-interacting factors possessing a wide range of cellular functions linked with this protein, including, but not limited to, coregulators associated with transcriptional activation and repression, DNA damage response, and DNA replication. Because chromatin remodeling activities are essential to developmental lineage decisions and adult cell function, our analysis focused on investigating the influence of the Swi/Snf chromatin remodeler on Pdx1 action. The two mutually exclusive and indispensable Swi/Snf core ATPase subunits, Brg1 and Brm, distinctly affected target gene expression in β cells. Furthermore, physiological and pathophysiological conditions dynamically regulated Pdx1 binding to these Swi/Snf complexes in vivo. We discuss how context-dependent recruitment of coregulatory complexes by Pdx1 could impact pancreas cell development and adult islet β cell activity.

  13. DQO Summary Report for 324 and 327 Building Hot Cells D4 Project Waste Characterization

    Energy Technology Data Exchange (ETDEWEB)

    T.A. Lee

    2006-02-06

    This data quality objective (DQO) summary report provides the results of the DQO process conducted for waste characterization activities for the 324 and 327 Building hot cells decommission, deactivate, decontaminate, and demolish activities. This DQO summary report addresses the systems and processes related to the hot cells, air locks, vaults, tanks, piping, basins, air plenums, air ducts, filters, an adjacent elements that have high dose rates, high contamination levels, and/or suspect transuranic waste, which will require nonstandard D4 techniques.

  14. A supersymmetric D4 model for μ-τ symmetry

    Science.gov (United States)

    Adulpravitchai, A.; Blum, A.; Hagedorn, C.

    2009-03-01

    We construct a supersymmeterized version of the model presented by Grimus and Lavoura (GL) in \\cite{GL1} which predicts θ23 maximal and θ13 = 0 in the lepton sector. For this purpose, we extend the flavor group, which is D4 × Z2(aux) in the original model, to D4 × Z5. An additional difference is the absence of right-handed neutrinos. Despite these changes the model is the same as the GL model, since θ23 maximal and θ13 = 0 arise through the same mismatch of D4 subgroups, D2 in the charged lepton and Z2 in the neutrino sector. In our setup D4 is solely broken by gauge singlets, the flavons. We show that their vacuum structure, which leads to the prediction of θ13 and θ23, is a natural result of the scalar potential. We find that the neutrino mass matrix only allows for inverted hierarchy, if we assume a certain form of spontaneous CP violation. The quantity |mee|, measured in neutrinoless double beta decay, is nearly equal to the lightest neutrino mass m3. The Majorana phases phi1 and phi2 are restricted to a certain range for m3lesssim0.06 eV. We discuss the next-to-leading order corrections which give rise to shifts in the vacuum expectation values of the flavons. These induce deviations from maximal atmospheric mixing and vanishing θ13. It turns out that these deviations are smaller for θ23 than for θ13.

  15. Tachyon condensation in the D0/D4 system

    International Nuclear Information System (INIS)

    David, Justin R.

    2000-01-01

    The D0/D4 system with a Neveu-Schwarz B-field in the spatial directions of the D4-brane has a tachyon in the spectrum of the (0,4) strings. The tachyon signals the instability of the system to form a bound state of the D0-brane with the D4-brane. We use the Wess-Zumino-Witten like open superstring field theory formulated by Berkovits to study the tachyon potential for this system. The tachyon potential lies outside the universality class of the D-brane anti-D-brane system. It is a function of the B-field. We calculate the tachyon potential at the zeroth level approximation. The minimum of the tachyon potential in this case is expected to reproduce the mass defect involved in the formation of the D0/D4 bound state. We compare the minimum of the tachyon potential with the mass defect in three cases. For small values of the B-field we obtain 70% of the expected mass defect. For large values of the B-field with Pf(2πα' B) > 0 the potential reduces to that of the D-brane anti-D-brane reproducing 62% of the expected mass defect. For large values of the B-field with Pf(2πα' B) < 0 the minimum of the tachyon potential gives 25% of the expected mass defect. At the tachyon condensate we show that the (0,4) strings decouple from the low energy dynamics. (author)

  16. Distinctive Citizenship

    DEFF Research Database (Denmark)

    Kaur, Ravinder

    2009-01-01

    The refugee, in India's Partition history, appears as an enigmatic construct - part pitiful, part heroic, though mostly shorn of agency - representing the surface of the human tragedy of Partition. Yet this archetype masks the undercurrent of social distinctions that produced hierarchies of post...

  17. Common and distinct DNA-binding and regulatory activities of the BEN-solo transcription factor family.

    Science.gov (United States)

    Dai, Qi; Ren, Aiming; Westholm, Jakub O; Duan, Hong; Patel, Dinshaw J; Lai, Eric C

    2015-01-01

    Recently, the BEN (BANP, E5R, and NAC1) domain was recognized as a new class of conserved DNA-binding domain. The fly genome encodes three proteins that bear only a single BEN domain ("BEN-solo" factors); namely, Insensitive (Insv), Bsg25A (Elba1), and CG9883 (Elba2). Insv homodimers preferentially bind CCAATTGG palindromes throughout the genome to mediate transcriptional repression, whereas Bsg25A and Elba2 heterotrimerize with their obligate adaptor, Elba3 (i.e., the ELBA complex), to recognize a CCAATAAG motif in the Fab-7 insulator. While these data suggest distinct DNA-binding properties of BEN-solo proteins, we performed reporter assays that indicate that both Bsg25A and Elba2 can individually recognize Insv consensus sites efficiently. We confirmed this by solving the structure of Bsg25A complexed to the Insv site, which showed that key aspects of the BEN:DNA recognition strategy are similar between these proteins. We next show that both Insv and ELBA proteins are competent to mediate transcriptional repression via Insv consensus sequences but that the ELBA complex appears to be selective for the ELBA site. Reciprocally, genome-wide analysis reveals that Insv exhibits significant cobinding to class I insulator elements, indicating that it may also contribute to insulator function. Indeed, we observed abundant Insv binding within the Hox complexes with substantial overlaps with class I insulators, many of which bear Insv consensus sites. Moreover, Insv coimmunoprecipitates with the class I insulator factor CP190. Finally, we observed that Insv harbors exclusive activity among fly BEN-solo factors with respect to regulation of Notch-mediated cell fate choices in the peripheral nervous system. This in vivo activity is recapitulated by BEND6, a mammalian BEN-solo factor that conserves the Notch corepressor function of Insv but not its capacity to bind Insv consensus sites. Altogether, our data define an array of common and distinct biochemical and functional

  18. Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans.

    Directory of Open Access Journals (Sweden)

    Michael A Petrie

    Full Text Available Skeletal muscle exercise regulates several important metabolic genes in humans. We know little about the effects of environmental stress (heat and mechanical stress (vibration on skeletal muscle. Passive mechanical stress or systemic heat stress are often used in combination with many active exercise programs. We designed a method to deliver a vibration stress and systemic heat stress to compare the effects with active skeletal muscle contraction.The purpose of this study is to examine whether active mechanical stress (muscle contraction, passive mechanical stress (vibration, or systemic whole body heat stress regulates key gene signatures associated with muscle metabolism, hypertrophy/atrophy, and inflammation/repair.Eleven subjects, six able-bodied and five with chronic spinal cord injury (SCI participated in the study. The six able-bodied subjects sat in a heat stress chamber for 30 minutes. Five subjects with SCI received a single dose of limb-segment vibration or a dose of repetitive electrically induced muscle contractions. Three hours after the completion of each stress, we performed a muscle biopsy (vastus lateralis or soleus to analyze mRNA gene expression.We discovered repetitive active muscle contractions up regulated metabolic transcription factors NR4A3 (12.45 fold, PGC-1α (5.46 fold, and ABRA (5.98 fold; and repressed MSTN (0.56 fold. Heat stress repressed PGC-1α (0.74 fold change; p < 0.05; while vibration induced FOXK2 (2.36 fold change; p < 0.05. Vibration similarly caused a down regulation of MSTN (0.74 fold change; p < 0.05, but to a lesser extent than active muscle contraction. Vibration induced FOXK2 (p < 0.05 while heat stress repressed PGC-1α (0.74 fold and ANKRD1 genes (0.51 fold; p < 0.05.These findings support a distinct gene regulation in response to heat stress, vibration, and muscle contractions. Understanding these responses may assist in developing regenerative rehabilitation interventions to improve muscle cell

  19. Differential Mechanisms for SHP2 Binding and Activation Are Exploited by Geographically Distinct Helicobacter pylori CagA Oncoproteins

    Directory of Open Access Journals (Sweden)

    Takeru Hayashi

    2017-09-01

    Full Text Available Helicobacter pylori East Asian CagA is more closely associated with gastric cancer than Western CagA. Here we show that, upon tyrosine phosphorylation, the East Asian CagA-specific EPIYA-D segment binds to the N-SH2 domain of pro-oncogenic SHP2 phosphatase two orders of magnitude greater than Western CagA-specific EPIYA-C. This high-affinity binding is achieved via cryptic interaction between Phe at the +5 position from phosphotyrosine in EPIYA-D and a hollow on the N-SH2 phosphopeptide-binding floor. Also, duplication of EPIYA-C in Western CagA, which increases gastric cancer risk, enables divalent high-affinity binding with SHP2 via N-SH2 and C-SH2. These strong CagA bindings enforce enzymatic activation of SHP2, which endows cells with neoplastic traits. Mechanistically, N-SH2 in SHP2 is in an equilibrium between stimulatory “relaxed” and inhibitory “squeezed” states, which is fixed upon high-affinity CagA binding to the “relaxed” state that stimulates SHP2. Accordingly, East Asian CagA and Western CagA exploit distinct mechanisms for SHP2 deregulation.

  20. Vascular effects of leukotriene D4 in human skin

    DEFF Research Database (Denmark)

    Bisgaard, H

    1987-01-01

    Leukotriene D4 (LTD4) increased the blood flow rate in human skin, equipotent to histamine in the dose range of 3.1-200 pmol. The vasodilatation lasted for up to 60 min, and no late reactions occurred. Indomethacin did not affect the LTD4-induced blood flow rate. H1 and H2 antagonists reduced...... as a mediator of the axon reflex, and show that LTD4 causes a direct vasodilatory effect that is not mediated via histamine or cyclooxygenase products. The laser-Doppler flowmeter was applied for dynamic studies of the vasopressor response in the skin during a Valsalva maneuver, and the relative changes...

  1. TCTEX1D4, a novel protein phosphatase 1 interactor: connecting the phosphatase to the microtubule network

    Science.gov (United States)

    Korrodi-Gregório, Luís; Vieira, Sandra I.; Esteves, Sara L. C.; Silva, Joana V.; Freitas, Maria João; Brauns, Ann-Kristin; Luers, Georg; Abrantes, Joana; Esteves, Pedro J.; da Cruz e Silva, Odete A. B.; Fardilha, Margarida; da Cruz e Silva, Edgar F.

    2013-01-01

    Summary Reversible phosphorylation plays an important role as a mechanism of intracellular control in eukaryotes. PPP1, a major eukaryotic Ser/Thr-protein phosphatase, acquires its specificity by interacting with different protein regulators, also known as PPP1 interacting proteins (PIPs). In the present work we characterized a physiologically relevant PIP in testis. Using a yeast two-hybrid screen with a human testis cDNA library, we identified a novel PIP of PPP1CC2 isoform, the T-complex testis expressed protein 1 domain containing 4 (TCTEX1D4) that has recently been described as a Tctex1 dynein light chain family member. The overlay assays confirm that TCTEX1D4 interacts with the different spliced isoforms of PPP1CC. Also, the binding domain occurs in the N-terminus, where a consensus PPP1 binding motif (PPP1BM) RVSF is present. The distribution of TCTEX1D4 in testis suggests its involvement in distinct functions, such as TGFβ signaling at the blood–testis barrier and acrosome cap formation. Immunofluorescence in human ejaculated sperm shows that TCTEX1D4 is present in the flagellum and in the acrosome region of the head. Moreover, TCTEX1D4 and PPP1 co-localize in the microtubule organizing center (MTOC) and microtubules in cell cultures. Importantly, the TCTEX1D4 PPP1BM seems to be relevant for complex formation, for PPP1 retention in the MTOC and movement along microtubules. These novel results open new avenues to possible roles of this dynein, together with PPP1. In essence TCTEX1D4/PPP1C complex appears to be involved in microtubule dynamics, sperm motility, acrosome reaction and in the regulation of the blood–testis barrier. PMID:23789093

  2. Digit Ratio (2D:4D) Predicts Self-Reported Measures of General Competitiveness, but Not Behavior in Economic Experiments.

    Science.gov (United States)

    Bönte, Werner; Procher, Vivien D; Urbig, Diemo; Voracek, Martin

    2017-01-01

    The ratio of index finger length to ring finger length (2D:4D) is considered to be a putative biomarker of prenatal androgen exposure (PAE), with previous research suggesting that 2D:4D is associated with human behaviors, especially sex-typical behaviors. This study empirically examines the relationship between 2D:4D and individual competitiveness, a behavioral trait that is found to be sexually dimorphic. We employ two related, but distinct, measures of competitiveness, namely behavioral measures obtained from economic experiments and psychometric self-reported measures. Our analyses are based on two independent data sets obtained from surveys and economic experiments with 461 visitors of a shopping mall (Study I) and 617 university students (Study II). The correlation between behavior in the economic experiment and digit ratios of both hands is not statistically significant in either study. In contrast, we find a negative and statistically significant relationship between psychometric self-reported measures of competitiveness and right hand digit ratios (R2D:4D) in both studies. This relationship is especially strong for younger people. Hence, this study provides some robust empirical evidence for a negative association between R2D:4D and self-reported competitiveness. We discuss potential reasons why digit ratio may relate differently to behaviors in specific economics experiments and to self-reported general competitiveness.

  3. Digit Ratio (2D:4D Predicts Self-Reported Measures of General Competitiveness, but Not Behavior in Economic Experiments

    Directory of Open Access Journals (Sweden)

    Werner Bönte

    2017-12-01

    Full Text Available The ratio of index finger length to ring finger length (2D:4D is considered to be a putative biomarker of prenatal androgen exposure (PAE, with previous research suggesting that 2D:4D is associated with human behaviors, especially sex-typical behaviors. This study empirically examines the relationship between 2D:4D and individual competitiveness, a behavioral trait that is found to be sexually dimorphic. We employ two related, but distinct, measures of competitiveness, namely behavioral measures obtained from economic experiments and psychometric self-reported measures. Our analyses are based on two independent data sets obtained from surveys and economic experiments with 461 visitors of a shopping mall (Study I and 617 university students (Study II. The correlation between behavior in the economic experiment and digit ratios of both hands is not statistically significant in either study. In contrast, we find a negative and statistically significant relationship between psychometric self-reported measures of competitiveness and right hand digit ratios (R2D:4D in both studies. This relationship is especially strong for younger people. Hence, this study provides some robust empirical evidence for a negative association between R2D:4D and self-reported competitiveness. We discuss potential reasons why digit ratio may relate differently to behaviors in specific economics experiments and to self-reported general competitiveness.

  4. Optogenetic Inhibition Reveals Distinct Roles for Basolateral Amygdala Activity at Discrete Time Points during Risky Decision Making.

    Science.gov (United States)

    Orsini, Caitlin A; Hernandez, Caesar M; Singhal, Sarthak; Kelly, Kyle B; Frazier, Charles J; Bizon, Jennifer L; Setlow, Barry

    2017-11-29

    Decision making is a multifaceted process, consisting of several distinct phases that likely require different cognitive operations. Previous work showed that the basolateral amygdala (BLA) is a critical substrate for decision making involving risk of punishment; however, it is unclear how the BLA is recruited at different stages of the decision process. To this end, the current study used optogenetics to inhibit the BLA during specific task phases in a model of risky decision making (risky decision-making task) in which rats choose between a small, "safe" reward and a large reward accompanied by varying probabilities of footshock punishment. Male Long-Evans rats received intra-BLA microinjections of viral vectors carrying either halorhodopsin (eNpHR3.0-mCherry) or mCherry alone (control) followed by optic fiber implants and were trained in the risky decision-making task. Laser delivery during the task occurred during intertrial interval, deliberation, or reward outcome phases, the latter of which was further divided into the three possible outcomes (small, safe; large, unpunished; large, punished). Inhibition of the BLA selectively during the deliberation phase decreased choice of the large, risky outcome (decreased risky choice). In contrast, BLA inhibition selectively during delivery of the large, punished outcome increased risky choice. Inhibition had no effect during the other phases, nor did laser delivery affect performance in control rats. Collectively, these data indicate that the BLA can either inhibit or promote choice of risky options, depending on the phase of the decision process in which it is active. SIGNIFICANCE STATEMENT To date, most behavioral neuroscience research on neural mechanisms of decision making has used techniques that preclude assessment of distinct phases of the decision process. Here we show that optogenetic inhibition of the BLA has opposite effects on choice behavior in a rat model of risky decision making, depending on the phase

  5. HIF-1alpha and HIF-2alpha are differentially activated in distinct cell populations in retinal ischaemia.

    Directory of Open Access Journals (Sweden)

    Freya M Mowat

    2010-06-01

    Full Text Available Hypoxia plays a key role in ischaemic and neovascular disorders of the retina. Cellular responses to oxygen are mediated by hypoxia-inducible transcription factors (HIFs that are stabilised in hypoxia and induce the expression of a diverse range of genes. The purpose of this study was to define the cellular specificities of HIF-1alpha and HIF-2alpha in retinal ischaemia, and to determine their correlation with the pattern of retinal hypoxia and the expression profiles of induced molecular mediators.We investigated the tissue distribution of retinal hypoxia during oxygen-induced retinopathy (OIR in mice using the bio-reductive drug pimonidazole. We measured the levels of HIF-1alpha and HIF-2alpha proteins by Western blotting and determined their cellular distribution by immunohistochemistry during the development of OIR. We measured the temporal expression profiles of two downstream mediators, vascular endothelial growth factor (VEGF and erythropoietin (Epo by ELISA. Pimonidazole labelling was evident specifically in the inner retina. Labelling peaked at 2 hours after the onset of hypoxia and gradually declined thereafter. Marked binding to Müller glia was evident during the early hypoxic stages of OIR. Both HIF-1alpha and HIF-2alpha protein levels were significantly increased during retinal hypoxia but were evident in distinct cellular distributions; HIF-1alpha stabilisation was evident in neuronal cells throughout the inner retinal layers whereas HIF-2alpha was restricted to Müller glia and astrocytes. Hypoxia and HIF-alpha stabilisation in the retina were closely followed by upregulated expression of the downstream mediators VEGF and EPO.Both HIF-1alpha and HIF-2alpha are activated in close correlation with retinal hypoxia but have contrasting cell specificities, consistent with differential roles in retinal ischaemia. Our findings suggest that HIF-2alpha activation plays a key role in regulating the response of Müller glia to hypoxia.

  6. Burden of Influenza in 4 Ecologically Distinct Regions of Peru: Household Active Surveillance of a Community Cohort, 2009-2015.

    Science.gov (United States)

    Tinoco, Yeny O; Azziz-Baumgartner, Eduardo; Uyeki, Timothy M; Rázuri, Hugo R; Kasper, Matthew R; Romero, Candice; Silva, Maria E; Simons, Mark P; Soto, Giselle M; Widdowson, Marc-Alain; Gilman, Robert H; Bausch, Daniel G; Montgomery, Joel M

    2017-10-16

    There are limited data on the burden of disease posed by influenza in low- and middle-income countries. Furthermore, most estimates of influenza disease burden worldwide rely on passive sentinel surveillance at health clinics and hospitals that lack accurate population denominators. We documented influenza incidence, seasonality, health-system utilization with influenza illness, and vaccination coverage through active community-based surveillance in 4 ecologically distinct regions of Peru over 6 years. Approximately 7200 people in 1500 randomly selected households were visited 3 times per week. Naso- and oropharyngeal swabs were collected from persons with influenza-like illness and tested for influenza virus by real-time reverse-transcription polymerase chain reaction. We followed participants for 35353 person-years (PY). The overall incidence of influenza was 100 per 1000 PY (95% confidence interval [CI], 97-104) and was highest in children aged 2-4 years (256/1000 PY [95% CI, 236-277]). Seasonal incidence trends were similar across sites, with 61% of annual influenza cases occurring during the austral winter (May-September). Of all participants, 44 per 1000 PY (95% CI, 42-46) sought medical care, 0.7 per 1000 PY (95% CI, 0.4-1.0) were hospitalized, and 1 person died (2.8/100000 PY). Influenza vaccine coverage was 27% among children aged 6-23 months and 26% among persons aged ≥65 years. Our results indicate that 1 in 10 persons develops influenza each year in Peru, with the highest incidence in young children. Active community-based surveillance allows for a better understanding of the true burden and seasonality of disease that is essential to plan the optimal target groups, timing, and cost of national influenza vaccination programs. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  7. Neonatal rearing conditions distinctly shape locus coeruleus neuronal activity, dendritic arborization, and sensitivity to corticotrophin-releasing factor

    Science.gov (United States)

    Swinny, Jerome D.; O'Farrell, Eimear; Bingham, Brian C.; Piel, David A.; Valentino, Rita J.; Beck, Sheryl G.

    2010-01-01

    Early life events influence vulnerability to psychiatric illness. This has been modelled in rats and it has been demonstrated that different durations of maternal separation shape adult endocrine and behavioural stress reactivity. One system through which maternal separation may act is the locus coeruleus (LC)–norepinephrine system that regulates emotional arousal. Here we demonstrate that different durations of maternal separation have distinct effects on LC physiology and dendritic morphology. Rat pups were separated from the dam for 15 min/d (HMS-15) or 180 min/d (HMS-180) from post-natal days 2–14. Others were either undisturbed (HMS-0) or were vendor-purchased controls. LC characteristics were compared at age 22–35 d using whole-cell recordings in vitro. Cells were filled with biocytin for morphological analysis. LC neurons of HMS-180 rats were tonically activated compared to HMS-15 and control rats, with firing rates that were 2-fold higher than these groups. Corticotrophin-releasing factor (CRF) application did not further activate LC neurons of HMS-180 rats but increased LC firing rate in HMS-0 and control rats. LC neurons of HMS-15 rats were resistant to excitation by CRF. Maternal separation also affected LC dendritic morphology. LC dendrites of HMS-15 rats exhibited less branching and decreased total dendritic length, an effect that could decrease the probability of contacting limbic afferents that terminate in the pericoerulear region. This effect may provide a structural basis for an attenuated magnitude of emotional arousal. Together, these results demonstrate long-term consequences of early life events on the LC–norepinephrine system that may shape adult behaviour. PMID:19653930

  8. On the hidden maxwell superalgebra underlying D = 4 supergravity

    Energy Technology Data Exchange (ETDEWEB)

    Penafiel, D.M. [Departamento de Fisica, Universidad de Concepcion (Chile); DISAT, Politecnico di Torino (Italy); Istituto Nazionale di Fisica Nucleare (INFN), Sezione di Torino (Italy); Ravera, L. [DISAT, Politecnico di Torino (Italy); Istituto Nazionale di Fisica Nucleare (INFN), Sezione di Torino (Italy)

    2017-09-15

    In this work, we expand the hidden AdS-Lorentz superalgebra underlying D = 4 supergravity, reaching a (hidden) Maxwell superalgebra. The latter can be viewed as an extension involving cosmological constant of the superalgebra underlying D = 4 supergravity in flat spacetime. We write the Maurer-Cartan equations in this context and we find some interesting extensions of the antisymmetric 3-form A{sup (3)} appearing in the Free Differential Algebra in Minkowski space. The structure of Free Differential Algebras is obtained by considering the zero curvature equations. We write the parametrization of A{sup (3)} in terms of 1-forms and we rend the topological features of its extensions manifest. We interestingly find out that the structure of these extensions, and consequently the structure of the corresponding boundary contribution dA{sup (3)}, strongly depends on the form of the extra fermionic generator appearing in the hidden Maxwell superalgebra. The model we develop in this work is defined in an enlarged superspace with respect to the ordinary one, and the extra bosonic and fermionic 1-forms required for the closure of the hidden Maxwell superalgebra must be considered as physical fields in this enlarged superspace. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  9. Synthesis of cyclophosphamide-4,4,5,5-d4

    International Nuclear Information System (INIS)

    Walsh, S.P.; Chang, Y.H.; Ludeman, S.M.

    1995-01-01

    3-Hydroxypropionitrile was subjected to a base-catalyzed exchange reaction in D 2 O which provided 2,2-dideuterio-3-deuteroxypropionitrile (DOCH 2 CD 2 CN) in 70% yield. Reduction of the nitrile with LiAID 4 gave 3-amino-2,2,3,3-tetradeuteriopropan-1-ol (HOCH 2 CD 2 CD 2 NH 2 ) in a crude yield of 71%. Reaction of this intermediate with N,N-bis(2-chloroethyl)phosphoramidic dichloride [Cl 2 P(O)N(CH 2 CH 2 Cl) 2 ] followed by the combination of those chromatography fractions which contained only pure material gave cyclophosphamide-4,4,5,5-d 4 as a white oil in 13% yield. A portion of this oil was converted to the monohydrate by the addition of water (1.1 equivalents) and crystallization from ether/petroleum ether (62% yield). For the hydrate, MS analyses gave an average mole percent enrichment (with average deviation over 5 determinations) of 89.1 ± 0.5% d 4 . (author)

  10. Beta2- and beta3-adrenoceptors activate glucose uptake in chick astrocytes by distinct mechanisms: a mechanism for memory enhancement?

    Science.gov (United States)

    Hutchinson, Dana S; Summers, Roger J; Gibbs, Marie E

    2007-11-01

    Isoprenaline, acting at beta-adrenoceptors (ARs), enhances memory formation in single trial discriminated avoidance learning in day-old chicks by mechanisms involving alterations in glucose and glycogen metabolism. Earlier studies of memory consolidation in chicks indicated that beta3-ARs enhanced memory by increasing glucose uptake, whereas beta2-ARs enhance memory by increasing glycogenolysis. This study examines the ability of beta-ARs to increase glucose uptake in chick forebrain astrocytes. The beta-AR agonist isoprenaline increased glucose uptake in a concentration-dependent manner, as did insulin. Glucose uptake was increased by the beta2-AR agonist zinterol and the beta3-AR agonist CL316243, but not by the beta1-AR agonist RO363. In chick astrocytes, reverse transcription-polymerase chain reaction studies showed that beta1-, beta2-, and beta3-AR mRNA were present, whereas radioligand-binding studies showed the presence of only beta2- and beta3-ARs. beta-AR or insulin-mediated glucose uptake was inhibited by phosphatidylinositol-3 kinase and protein kinase C inhibitors, suggesting a possible interaction between the beta-AR and insulin pathways. However beta2- and beta3-ARs increase glucose uptake by two different mechanisms: beta2-ARs via a Gs-cAMP-protein kinase A-dependent pathway, while beta3-ARs via interactions with Gi. These results indicate that activation of beta2- and beta3-ARs causes glucose uptake in chick astrocytes by distinct mechanisms, which may be relevant for memory enhancement.

  11. An enriched rearing environment calms adult male rat sexual activity: implication for distinct serotonergic and hormonal responses to females.

    Directory of Open Access Journals (Sweden)

    Susumu Urakawa

    Full Text Available Early life events induce alterations in neural function in adulthood. Although rearing in an enriched environment (EE has a great impact on behavioral development, the effects of enriched rearing on sociosexual behavior remain unclear. In this study, we investigated the effects of rearing in an EE on male copulatory behavior and its underlying neurobiological mechanisms in Wistar-Imamichi rats. Three-week-old, recently weaned rats were continuously subjected to a standard environment (SE or an EE comprised of a large cage with several objects, such as toys, tunnels, ladders, and a running wheel. After 6 weeks, rats reared in an EE (EE rats showed decreased sexual activity compared with rats reared in a SE (SE rats. This included a lower number of ejaculations and longer latencies in three consecutive copulatory tests. In addition, EE rats showed decreased emotional responsiveness and less locomotor behavior in an open field. In a runway test, on the other hand, sexual motivation toward receptive females in EE males was comparable to that of SE males. Furthermore, following exposure to a female, increases in serotonin levels in the nucleus accumbens and the striatum were significantly suppressed in EE males, whereas dopaminergic responses were similar between the groups. Female-exposure-induced increases in the levels of plasma corticosterone and testosterone were also suppressed in EE rats compared to SE rats. These data suggest that rearing in an EE decreases male copulatory behavior, and serotonin and hormonal regulating systems may regulate the differences in sociosexual interactions that result from distinct rearing environments.

  12. Distinctive proteolytic activity of cell envelope proteinase of Lactobacillus helveticus isolated from airag, a traditional Mongolian fermented mare's milk.

    Science.gov (United States)

    Miyamoto, Mari; Ueno, Hiroshi M; Watanabe, Masayuki; Tatsuma, Yumi; Seto, Yasuyuki; Miyamoto, Taku; Nakajima, Hadjime

    2015-03-16

    Airag is a traditional fermented milk of Mongolia that is usually made from raw mare's milk. Lactobacillus helveticus is one of the lactic acid bacteria most frequently isolated from airag. In this study, we investigated the genetic and physiological characteristics of L. helveticus strains isolated from airag and clarified their significance in airag by comparing them with strains from different sources. Six strains of L. helveticus were isolated from five home-made airag samples collected from different regions of Mongolia. The optimal temperature for acidification in skim milk was 30 to 35°C for all the Mongolian strains, which is lower than those for the reference strains (JCM 1554 and JCM 1120(T)) isolated from European cheeses. All of the strains had a prtH1-like gene encoding a variant type of cell envelope proteinase (CEP). The CEP amino acid sequence in Snow Brand Typeculture (SBT) 11087 isolated from airag shared 71% identity with PrtH of L. helveticus CNRZ32 (AAD50643.1) but 98% identity with PrtH of Lactobacillus kefiranofaciens ZW3 (AEG40278.1) isolated from a traditional fermented milk in Tibet. The proteolytic activities of the CEP from SBT11087 on artificial substrate (N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide) and pure casein were measured using an intact-cell degradation assay. The activity of the CEP from SBT11087 was observed to be weak and exhibited a lower optimal temperature (40°C) than those from the reference strains (45-50°C). The specificity of the SBT11087 CEP for αS1-casein was typical of the CEPs previously reported in L. helveticus, as determined through the degradation profiles obtained through gel electrophoresis and mass spectrometry analyses. In contrast, the degradation profile of β-casein revealed that the CEP of SBT11087 primarily hydrolyzes its C-terminal domain and hydrolyzed nine of the 16 cleavage sites shared among the CEPs of other L. helveticus strains. Thus, the CEP of SBT11087 is distinct from those from

  13. Discrete Torsion, (Anti) de Sitter D4-Brane and Tunneling

    Science.gov (United States)

    Singh, Abhishek K.; Pandey, P. K.; Singh, Sunita; Kar, Supriya

    2014-06-01

    We obtain quantum geometries on a vacuum created pair of a (DDbar)3-brane, at a Big Bang singularity, by a local two form on a D4-brane. In fact our analysis is provoked by an established phenomenon leading to a pair creation by a gauge field at a black hole horizon by Stephen Hawking in 1975. Importantly, the five dimensional microscopic black holes are described by an effective non-perturbative curvature underlying a discrete torsion in a second order formalism. In the case for a non-propagating torsion, the effective curvature reduces to Riemannian, which in a low energy limit may describe Einstein vacuum in the formalism. In particular, our analysis suggests that a non-trivial space begin with a hot de Sitter brane-Universe underlying a nucleation of a vacuum pair of (DDbar)-instanton at a Big Bang. A pair of instanton nucleats a D-particle which in turn combines with an anti D-particle to describe a D-string and so on. The nucleation of a pair of higher dimensional pair of brane/anti-brane from a lower dimensional pair may be viewed via an expansion of the brane-Universe upon time. It is in conformity with the conjecture of a branes within a brane presumably in presence of the non-zero modes of two form. Interestingly, we perform a thermal analysis underlying various emergent quantum de Sitter vacua on a D4-brane and argue for the plausible tunneling geometries underlying a thermal equilibrium. It is argued that a de Sitter Schwarzschild undergoes quantum tunneling to an AdS-brane Schwarzschild via Nariai and de Sitter topological black hole.

  14. Discrete Torsion, (Anti) de Sitter D4-Brane and Tunneling

    International Nuclear Information System (INIS)

    Singh, Abhishek K.; Pandey, P.K.; Singh, Sunita; Kar, Supriya

    2014-01-01

    We obtain quantum geometries on a vacuum created pair of a (DD ¯ ) 3 -brane, at a Big Bang singularity, by a local two form on a D 4 -brane. In fact our analysis is provoked by an established phenomenon leading to a pair creation by a gauge field at a black hole horizon by Stephen Hawking in 1975. Importantly, the five dimensional microscopic black holes are described by an effective non-perturbative curvature underlying a discrete torsion in a second order formalism. In the case for a non-propagating torsion, the effective curvature reduces to Riemannian, which in a low energy limit may describe Einstein vacuum in the formalism. In particular, our analysis suggests that a non-trivial space begin with a hot de Sitter brane-Universe underlying a nucleation of a vacuum pair of (DD ¯ )-instanton at a Big Bang. A pair of instanton nucleats a D-particle which in turn combines with an anti D-particle to describe a D-string and so on. The nucleation of a pair of higher dimensional pair of brane/anti-brane from a lower dimensional pair may be viewed via an expansion of the brane-Universe upon time. It is in conformity with the conjecture of a branes within a brane presumably in presence of the non-zero modes of two form. Interestingly, we perform a thermal analysis underlying various emergent quantum de Sitter vacua on a D 4 -brane and argue for the plausible tunneling geometries underlying a thermal equilibrium. It is argued that a de Sitter Schwarzschild undergoes quantum tunneling to an AdS-brane Schwarzschild via Nariai and de Sitter topological black hole

  15. Relationships of Smiling and Flirtation to Aggression and 2D:4D, a Prenatal Androgen Index

    Directory of Open Access Journals (Sweden)

    Leslie Burton

    2011-01-01

    Full Text Available Smiling has been reported to be a signal of submission/lower status, or a sign of cooperation. In the present study, use of smiling and flirtation to “make people receptive to my ideas” was conceptualized as mild aggression, since it is mildly manipulative of the perception of others as to one's internal emotional status. For 91 participants (55 female, 36 male, use of smiling and flirtation to make others receptive to one's ideas were associated with relational aggression and a more male-typical (smaller right 2D:4D finger length ratio. The only significant relationship in the male sample alone was the relationship between smiling and relational aggression. In the female sample alone, use of smiling and flirtation to “make people receptive to my ideas” was associated with a more male-typical 2D:4D finger length ratio pattern, and there was a trend for flirtation to be associated with greater physical aggression. Both 2D:4D and physical aggression have been associated with higher prenatal androgen level. It is concluded that deliberate smiling and flirtation are mild forms of relational aggression, and are related to prenatal androgenic activity in a manner similar to physical aggression. These findings are discussed in terms of the different evolutionary strategies of men and women to control their social environments.

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

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Yosuke; Shimizu, Taro; Mima, Yu [Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima, 1-78-1, Sho-machi, Tokushima 770-8505 (Japan); Abu Lila, Amr S. [Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima, 1-78-1, Sho-machi, Tokushima 770-8505 (Japan); Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Sharqia Governorate, Zagazig 44519 (Egypt); Ishida, Tatsuhiro, E-mail: ishida@tokushima-u.ac.jp [Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima, 1-78-1, Sho-machi, Tokushima 770-8505 (Japan); Kiwada, Hiroshi [Department of Pharmacokinetics and Biopharmaceutics, Subdivision of Biopharmaceutical Sciences, Institute of Health Biosciences, The University of Tokushima, 1-78-1, Sho-machi, Tokushima 770-8505 (Japan)

    2014-05-15

    PEGylation, the attachment of polyethylene glycol (PEG) to nanocarriers and proteins, is a widely accepted approach to improving the in vivo efficacy of the non-PEGylated products. However, both PEGylated liposomes and PEGylated proteins reportedly trigger the production of specific antibodies, mainly IgM, against the PEG moiety, which possibly leads to a reduction in safety and therapeutic efficacy of the PEGylated products. In the present study, two monoclonal anti-PEG IgMs — HIK-M09 via immunization with an intravenous injection of PEGylated liposomes (SLs) and HIK-M11 via immunization with a subcutaneous administration of PEGylated ovalbumin (PEG-OVA) were successfully generated. The generated IgMs showed efficient reactivity to mPEG{sub 2000} conjugated to 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine (DSPE), PEGylated liposome (SL) and PEG-OVA. It appears that HIK-M09 recognizes ethoxy (OCH{sub 2}CH{sub 2}) repeat units along with a terminal motif of PEG, while HIK-M11 recognizes only ethoxy repeat units of PEG. Such unique properties allow HIK-M09 to bind with dense PEG. In addition, their impact on the in vivo clearance of the PEGylated products was investigated. It was found that the generated ant-PEG IgMs induced a clearance of SL as they were intravenously administered with SL. Interestingly, the HIK-M11, generated by PEG-OVA, induced the clearance of both SL and PEG-OVA, while the HIK-M09, generated by SL, induced the clearance of SL only. We here revealed that the presence of serum anti-PEG IgM and the subsequent binding of anti-PEG IgM to the PEGylated products are not necessarily related to the enhanced clearance of the products. It appears that subsequent complement activation following anti-PEG IgM binding is the most important step in dictating the in vivo fate of PEGylated products. This study may have implications for the design, development and clinical application of PEGylated products and therapeutics. - Highlights: • Two monoclonal

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

    International Nuclear Information System (INIS)

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

    2014-01-01

    PEGylation, the attachment of polyethylene glycol (PEG) to nanocarriers and proteins, is a widely accepted approach to improving the in vivo efficacy of the non-PEGylated products. However, both PEGylated liposomes and PEGylated proteins reportedly trigger the production of specific antibodies, mainly IgM, against the PEG moiety, which possibly leads to a reduction in safety and therapeutic efficacy of the PEGylated products. In the present study, two monoclonal anti-PEG IgMs — HIK-M09 via immunization with an intravenous injection of PEGylated liposomes (SLs) and HIK-M11 via immunization with a subcutaneous administration of PEGylated ovalbumin (PEG-OVA) were successfully generated. The generated IgMs showed efficient reactivity to mPEG 2000 conjugated to 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine (DSPE), PEGylated liposome (SL) and PEG-OVA. It appears that HIK-M09 recognizes ethoxy (OCH 2 CH 2 ) repeat units along with a terminal motif of PEG, while HIK-M11 recognizes only ethoxy repeat units of PEG. Such unique properties allow HIK-M09 to bind with dense PEG. In addition, their impact on the in vivo clearance of the PEGylated products was investigated. It was found that the generated ant-PEG IgMs induced a clearance of SL as they were intravenously administered with SL. Interestingly, the HIK-M11, generated by PEG-OVA, induced the clearance of both SL and PEG-OVA, while the HIK-M09, generated by SL, induced the clearance of SL only. We here revealed that the presence of serum anti-PEG IgM and the subsequent binding of anti-PEG IgM to the PEGylated products are not necessarily related to the enhanced clearance of the products. It appears that subsequent complement activation following anti-PEG IgM binding is the most important step in dictating the in vivo fate of PEGylated products. This study may have implications for the design, development and clinical application of PEGylated products and therapeutics. - Highlights: • Two monoclonal anti-PEG Ig

  18. Distinctly December.

    Science.gov (United States)

    Instructor, 1982

    1982-01-01

    This special section presents Christmas and Hanukkah holiday activities and describes decorations and gifts that children can make. Other seasonal ideas include a Christmas luau dance, a magic Christmas tree, and Christmas and Hanukkah games and stories. (PP)

  19. 100 Area D4 Project Building Completion Report: December 2008 to December 2009

    International Nuclear Information System (INIS)

    Finucane, K.G.; Harrie, J.P.

    2010-01-01

    This report documents the final status of buildings after the completion of D4 activities at the 100 Area of the U.S. Department of Energy Hanford Site from December 1, 2008, to December 31, 2009. The following buildings are included in this report: 11-N Change Room; 13-N Storage Building; 107-N Basin Recirculation Facility; 108-N Chemical Unloading Facility; 183-ND Resin Disposal Pit; 183-F Clearwells; 188-D Ash Disposal Pit; 1524-N Hazardous Waste Storage Pad; 1525-N Laydown Storage Area; 1607-Ni Sewage Tank; 1607-N2 Sewage Tank; 1706-NA Sewage Lift Station; 1904-D Outfall Structure; MO-013 Mobile Office Trailer; MO-422 Mobile Office Trailer; and MO-999 Mobile Office Trailer. Demolition debris and soil associated with completion of these buildings were disposed at the Environmental Restoration Disposal Facility (ERDF), located at the Hanford Site. Postdemolition direct hand instrument surveys and Global Positioning Environmental Radiological Survey (GPERS) surveys were performed on excavations after loadout of debris and prior to backfill. The 100 Area D4/Interim Safe Storage (ISS) project personnel worked a total of approximately 137,930 hours (manual and non-manual, not including subcontractors) from December 1, 2008, to December 31, 2009. During this time there were 10 Occupational Safety and Health Administration (OSHA) recordable injuries, two of which involved lost time. There also were 27 first aid cases during this time period. No clothing contamination and no skin contamination incidents occurred during demolition of the 100 Area buildings. Workers received 7,350.2 person-mrem of radiological exposure from December 1, 2008, to December 31, 2009 during their support of D4 activities associated with the buildings discussed in this report. All boundary air sample results were below procedural action levels for the duration of the work performed.

  20. Drosophila Longevity Assurance Conferred by Reduced Insulin Receptor Substrate Chico Partially Requires d4eBP.

    Directory of Open Access Journals (Sweden)

    Hua Bai

    Full Text Available Mutations of the insulin/IGF signaling (IIS pathway extend Drosophila lifespan. Based on genetic epistasis analyses, this longevity assurance is attributed to downstream effects of the FOXO transcription factor. However, as reported FOXO accounts for only a portion of the observed longevity benefit, suggesting there are additional outputs of IIS to mediate aging. One candidate is target of rapamycin complex 1 (TORC1. Reduced TORC1 activity is reported to slow aging, whereas reduced IIS is reported to repress TORC1 activity. The eukaryotic translation initiation factor 4E binding protein (4E-BP is repressed by TORC1, and activated 4E-BP is reported to increase Drosophila lifespan. Here we use genetic epistasis analyses to test whether longevity assurance mutants of chico, the Drosophila insulin receptor substrate homolog, require Drosophila d4eBP to slow aging. In chico heterozygotes, which are robustly long-lived, d4eBP is required but not sufficient to slow aging. Remarkably, d4eBP is not required or sufficient for chico homozygotes to extend longevity. Likewise, chico heterozygote females partially require d4eBP to preserve age-dependent locomotion, and both chico genotypes require d4eBP to improve stress-resistance. Reproduction and most measures of growth affected by either chico genotype are always independent of d4eBP. In females, chico heterozygotes paradoxically produce more rather than less phosphorylated 4E-BP (p4E-BP. Altered IRS function within the IIS pathway of Drosophila appears to have partial, conditional capacity to regulate aging through an unconventional interaction with 4E-BP.

  1. Characterization of recombinant Mal d 4 and its application for component-resolved diagnosis of apple allergy

    NARCIS (Netherlands)

    Ma, Y.; Zuidmeer, L.; Bohle, B.; Bolhaar, S. T. H.; Gadermaier, G.; Gonzalez-Mancebo, E.; Fernandez-Rivas, M.; Knulst, A. C.; Himly, M.; Asero, R.; Ebner, C.; van Ree, R.; Ferreira, F.; Breiteneder, H.; Hoffmann-Sommergruber, K.

    2006-01-01

    BACKGROUND: Profilins are ubiquitous panallergens that have been extensively characterized; yet, their clinical relevance is still unclear. OBJECTIVE: The aim of the present study was to produce recombinant apple profilin (rMal d 4) and to evaluate its allergenic activity and its potency for

  2. Figure-ground segregation requires two distinct periods of activity in V1: a transcranial magnetic stimulation study.

    Science.gov (United States)

    Heinen, Klaartje; Jolij, Jacob; Lamme, Victor A F

    2005-09-08

    Discriminating objects from their surroundings by the visual system is known as figure-ground segregation. This process entails two different subprocesses: boundary detection and subsequent surface segregation or 'filling in'. In this study, we used transcranial magnetic stimulation to test the hypothesis that temporally distinct processes in V1 and related early visual areas such as V2 or V3 are causally related to the process of figure-ground segregation. Our results indicate that correct discrimination between two visual stimuli, which relies on figure-ground segregation, requires two separate periods of information processing in the early visual cortex: one around 130-160 ms and the other around 250-280 ms.

  3. Progress of study on the dopamine D4 receptor imaging agent

    International Nuclear Information System (INIS)

    Tian Haibin; Zhang Lan; Zhang Chunfu; Li Junling; Yin Duanzhi

    2001-01-01

    Dopamine receptors were originally classified into five receptors subtypes, the dopamine D 4 receptor was included. Schizophrenic pathophysiology may be associated with expression and function of the dopamine D 4 receptor; it is of great importance to study the imaging agent of dopamine D 4 receptor. The study on radioactivity distribution and metabolize of radioligand remains hampered by the lack radioligand for the D 4 receptor which can be labeled using suitable nuclei. This paper reviews the progress of study on the dopamine D 4 receptor imaging agent, with particular emphasis vary nuclei, for example 11 C, 18 F, 123 I, labeled D 4 receptor ligands, antagonists and analogs as PET or SPECT imaging agents. Authors estimated affinity and selectivity of radioligands for the dopamine D 4 receptor in laboratory animal tests

  4. Mycobacterial secretion systems ESX-1 and ESX-5 play distinct roles in host cell death and inflammasome activation

    KAUST Repository

    Abdallah, Abdallah; Bestebroer, Jovanka; Savage, Nigel D L; De Punder, Karin; Van Zon, Maaike; Wilson, Louis D.; Korbee, Cees J.; Van Der Sar, Astrid M.; Ottenhoff, Tom Hm M; Van Der Wel, Nicole N.; Bitter, Wilbert M.; Peters, Peter J.

    2011-01-01

    for the translocation of Mycobacterium tuberculosis or Mycobacterium marinum to the cytosol of host cells. However, the M. marinum ESX-5 mutant does not induce inflammasome activation and IL-1b activation. The ESX-5 system also induces a caspase-independent cell death

  5. Two distinct expression patterns of urokinase, urokinase receptor and plasminogen activator inhibitor-1 in colon cancer liver metastases

    DEFF Research Database (Denmark)

    Illemann, Martin; Bird, Nigel; Majeed, Ali

    2009-01-01

    Metastatic growth and invasion by colon cancer cells in the liver requires the ability of the cancer cells to interact with the new tissue environment. Plasmin(ogen) is activated on cell surfaces by urokinase-type PA (uPA), and is regulated by uPAR and plasminogen activator inhibitor-1 (PAI-1). T...

  6. Optogenetic activation of CA1 pyramidal neurons at the dorsal and ventral hippocampus evokes distinct brain-wide responses revealed by mouse fMRI.

    Directory of Open Access Journals (Sweden)

    Norio Takata

    Full Text Available The dorsal and ventral hippocampal regions (dHP and vHP are proposed to have distinct functions. Electrophysiological studies have revealed intra-hippocampal variances along the dorsoventral axis. Nevertheless, the extra-hippocampal influences of dHP and vHP activities remain unclear. In this study, we compared the spatial distribution of brain-wide responses upon dHP or vHP activation and further estimate connection strengths between the dHP and the vHP with corresponding extra-hippocampal areas. To achieve this, we first investigated responses of local field potential (LFP and multi unit activities (MUA upon light stimulation in the hippocampus of an anesthetized transgenic mouse, whose CA1 pyramidal neurons expressed a step-function opsin variant of channelrhodopsin-2 (ChR2. Optogenetic stimulation increased hippocampal LFP power at theta, gamma, and ultra-fast frequency bands, and augmented MUA, indicating light-induced activation of CA1 pyramidal neurons. Brain-wide responses examined using fMRI revealed that optogenetic activation at the dHP or vHP caused blood oxygenation level-dependent (BOLD fMRI signals in situ. Although activation at the dHP induced BOLD responses at the vHP, the opposite was not observed. Outside the hippocampal formation, activation at the dHP, but not the vHP, evoked BOLD responses at the retrosplenial cortex (RSP, which is in line with anatomical evidence. In contrast, BOLD responses at the lateral septum (LS were induced only upon vHP activation, even though both dHP and vHP send axonal fibers to the LS. Our findings suggest that the primary targets of dHP and vHP activation are distinct, which concurs with attributed functions of the dHP and RSP in spatial memory, as well as of the vHP and LS in emotional responses.

  7. Distinct summer and winter bacterial communities in the active layer of Svalbard permafrost revealed by DNA- and RNA-based analyses

    DEFF Research Database (Denmark)

    Schostag, Morten; Stibal, Marek; Jacobsen, Carsten S.

    2015-01-01

    organic matter on the bacterial communities. The copy number of 16S rRNA genes and transcripts revealed no distinct seasonal changes indicating potential bacterial activity during winter despite soil temperatures well below -10ºC. Multivariate statistical analysis of the bacterial diversity data (DNA......The active layer of soil overlaying permafrost in the Arctic is subjected to dramatic annual changes in temperature and soil chemistry, which likely affect bacterial activity and community structure. We studied seasonal variations in the bacterial community of active layer soil from Svalbard (78º......N) by co-extracting DNA and RNA from 12 soil cores collected monthly over a year. PCR amplicons of 16S rRNA genes (DNA) and reverse transcribed transcripts (cDNA) were quantified and sequenced to test for the effect of low winter temperature and seasonal variation in concentration of easily degradable...

  8. Serotonin 2C receptor activates a distinct population of arcuate pro-opiomelanocortin neurons via TRPC channels

    Science.gov (United States)

    Serotonin 2C receptors (5-HT2CRs) expressed by pro-opiomelanocortin (POMC) neurons of hypothalamic arcuate nucleus regulate food intake, energy homeostasis ,and glucose metabolism. However, the cellular mechanisms underlying the effects of 5-HT to regulate POMC neuronal activity via 5-HT2CRs have no...

  9. MMTV-Wnt1 and -DeltaN89beta-catenin induce canonical signaling in distinct progenitors and differentially activate Hedgehog signaling within mammary tumors.

    Directory of Open Access Journals (Sweden)

    Brigitte Teissedre

    Full Text Available Canonical Wnt/beta-catenin signaling regulates stem/progenitor cells and, when perturbed, induces many human cancers. A significant proportion of human breast cancer is associated with loss of secreted Wnt antagonists and mice expressing MMTV-Wnt1 and MMTV-DeltaN89beta-catenin develop mammary adenocarcinomas. Many studies have assumed these mouse models of breast cancer to be equivalent. Here we show that MMTV-Wnt1 and MMTV-DeltaN89beta-catenin transgenes induce tumors with different phenotypes. Using axin2/conductin reporter genes we show that MMTV-Wnt1 and MMTV-DeltaN89beta-catenin activate canonical Wnt signaling within distinct cell-types. DeltaN89beta-catenin activated signaling within a luminal subpopulation scattered along ducts that exhibited a K18(+ER(-PR(-CD24(highCD49f(low profile and progenitor properties. In contrast, MMTV-Wnt1 induced canonical signaling in K14(+ basal cells with CD24/CD49f profiles characteristic of two distinct stem/progenitor cell-types. MMTV-Wnt1 produced additional profound effects on multiple cell-types that correlated with focal activation of the Hedgehog pathway. We document that large melanocytic nevi are a hitherto unreported hallmark of early hyperplastic Wnt1 glands. These nevi formed along the primary mammary ducts and were associated with Hedgehog pathway activity within a subset of melanocytes and surrounding stroma. Hh pathway activity also occurred within tumor-associated stromal and K14(+/p63(+ subpopulations in a manner correlated with Wnt1 tumor onset. These data show MMTV-Wnt1 and MMTV-DeltaN89beta-catenin induce canonical signaling in distinct progenitors and that Hedgehog pathway activation is linked to melanocytic nevi and mammary tumor onset arising from excess Wnt1 ligand. They further suggest that Hedgehog pathway activation maybe a critical component and useful indicator of breast tumors arising from unopposed Wnt1 ligand.

  10. Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans.

    Science.gov (United States)

    Petrie, Michael A; Kimball, Amy L; McHenry, Colleen L; Suneja, Manish; Yen, Chu-Ling; Sharma, Arpit; Shields, Richard K

    2016-01-01

    Skeletal muscle exercise regulates several important metabolic genes in humans. We know little about the effects of environmental stress (heat) and mechanical stress (vibration) on skeletal muscle. Passive mechanical stress or systemic heat stress are often used in combination with many active exercise programs. We designed a method to deliver a vibration stress and systemic heat stress to compare the effects with active skeletal muscle contraction. The purpose of this study is to examine whether active mechanical stress (muscle contraction), passive mechanical stress (vibration), or systemic whole body heat stress regulates key gene signatures associated with muscle metabolism, hypertrophy/atrophy, and inflammation/repair. Eleven subjects, six able-bodied and five with chronic spinal cord injury (SCI) participated in the study. The six able-bodied subjects sat in a heat stress chamber for 30 minutes. Five subjects with SCI received a single dose of limb-segment vibration or a dose of repetitive electrically induced muscle contractions. Three hours after the completion of each stress, we performed a muscle biopsy (vastus lateralis or soleus) to analyze mRNA gene expression. We discovered repetitive active muscle contractions up regulated metabolic transcription factors NR4A3 (12.45 fold), PGC-1α (5.46 fold), and ABRA (5.98 fold); and repressed MSTN (0.56 fold). Heat stress repressed PGC-1α (0.74 fold change; p muscle contraction. Vibration induced FOXK2 (p muscle contractions. Understanding these responses may assist in developing regenerative rehabilitation interventions to improve muscle cell development, growth, and repair.

  11. A camel-derived MERS-CoV with a variant spike protein cleavage site and distinct fusion activation properties

    Science.gov (United States)

    Millet, Jean Kaoru; Goldstein, Monty E; Labitt, Rachael N; Hsu, Hung-Lun; Daniel, Susan; Whittaker, Gary R

    2016-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) continues to circulate in both humans and camels, and the origin and evolution of the virus remain unclear. Here we characterize the spike protein of a camel-derived MERS-CoV (NRCE-HKU205) identified in 2013, early in the MERS outbreak. NRCE-HKU205 spike protein has a variant cleavage motif with regard to the S2′ fusion activation site—notably, a novel substitution of isoleucine for the otherwise invariant serine at the critical P1′ cleavage site position. The substitutions resulted in a loss of furin-mediated cleavage, as shown by fluorogenic peptide cleavage and western blot assays. Cell–cell fusion and pseudotyped virus infectivity assays demonstrated that the S2′ substitutions decreased spike-mediated fusion and viral entry. However, cathepsin and trypsin-like protease activation were retained, albeit with much reduced efficiency compared with the prototypical EMC/2012 human strain. We show that NRCE-HKU205 has more limited fusion activation properties possibly resulting in more restricted viral tropism and may represent an intermediate in the complex pattern of MERS-CoV ecology and evolution. PMID:27999426

  12. Active fragments from pro- and antiapoptotic BCL-2 proteins have distinct membrane behavior reflecting their functional divergence.

    Directory of Open Access Journals (Sweden)

    Yannis Guillemin

    Full Text Available BACKGROUND: The BCL-2 family of proteins includes pro- and antiapoptotic members acting by controlling the permeabilization of mitochondria. Although the association of these proteins with the outer mitochondrial membrane is crucial for their function, little is known about the characteristics of this interaction. METHODOLOGY/PRINCIPAL FINDINGS: Here, we followed a reductionist approach to clarify to what extent membrane-active regions of homologous BCL-2 family proteins contribute to their functional divergence. Using isolated mitochondria as well as model lipid Langmuir monolayers coupled with Brewster Angle Microscopy, we explored systematically and comparatively the membrane activity and membrane-peptide interactions of fragments derived from the central helical hairpin of BAX, BCL-xL and BID. The results show a connection between the differing abilities of the assayed peptide fragments to contact, insert, destabilize and porate membranes and the activity of their cognate proteins in programmed cell death. CONCLUSION/SIGNIFICANCE: BCL-2 family-derived pore-forming helices thus represent structurally analogous, but functionally dissimilar membrane domains.

  13. Murine Lupus Susceptibility Locus Sle2 Activates DNA-Reactive B Cells through Two Sub-Loci with Distinct Phenotypes

    Science.gov (United States)

    Zeumer, Leilani; Sang, Allison; Niu, Haitao; Morel, Laurence

    2010-01-01

    The NZM2410-derived Sle2 lupus susceptibility locus induces an abnormal B cell differentiation which most prominently leads to the expansion of autoreactive B1a cells. We have mapped the expansion of B1a cells to three Sle2 sub-loci, Sle2a, Sle2b, and Sle2c. Sle2 also enhances the breach of B cell tolerance to nuclear antigens in the 56R anti-DNA immunoglobulin transgenic (Tg) model. This study used the Sle2 sub-congenic strains to map the activation of 56R Tg B cells. Sle2c strongly sustained the breach of tolerance and the activation of anti-DNA B cells. The production of Tg-encoded anti-DNA antibodies was more modest in Sle2a expressing mice, but Sle2a was responsible for the recruitment for Tg B cells to the marginal zone, a phenotype that has been found for 56R Tg B cells in mice expressing the whole Sle2 interval. In addition, Sle2a promoted the production of endogenously encoded anti-DNA antibodies. Overall, this study showed that at least two Sle2 genes are involved in the activation of anti-DNA B cells, and excluded more than two-thirds of the Sle2 interval from contributing to this phenotype. This constitutes an important step toward the identification of novel genes that play a critical role in B cell tolerance. PMID:21270826

  14. Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 1 Nef Proteins Show Distinct Patterns and Mechanisms of Src Kinase Activation

    Science.gov (United States)

    Greenway, Alison L.; Dutartre, Hélène; Allen, Kelly; McPhee, Dale A.; Olive, Daniel; Collette, Yves

    1999-01-01

    The nef gene from human and simian immunodeficiency viruses (HIV and SIV) regulates cell function and viral replication, possibly through binding of the nef product to cellular proteins, including Src family tyrosine kinases. We show here that the Nef protein encoded by SIVmac239 interacts with and also activates the human Src kinases Lck and Hck. This is in direct contrast to the inhibitory effect of HIV type 1 (HIV-1) Nef on Lck catalytic activity. Unexpectedly, however, the interaction of SIV Nef with human Lck or Hck is not mediated via its consensus proline motif, which is known to mediate HIV-1 Nef binding to Src homology 3 (SH3) domains, and various experimental analyses failed to show significant interaction of SIV Nef with the SH3 domain of either kinase. Instead, SIV Nef can bind Lck and Hck SH2 domains, and its N-terminal 50 amino acid residues are sufficient for Src kinase binding and activation. Our results provide evidence for multiple mechanisms by which Nef binds to and regulates Src kinases. PMID:10364375

  15. Effects of added dopants on various triboluminescent properties of europium dibenzoylmethide triethylammonium (EuD4TEA)

    Science.gov (United States)

    Owens, Constance; Fontenot, Ross S.; Bhat, Kamala N.; Aggarwal, Mohan D.

    2014-03-01

    A triboluminescent (TL) material is one that emits light upon pressure, impact, friction, or mechanical shock. TL materials are desirable for investigation because they have the potential to be used as the active element for smart impact sensors. While the material europium dibenzoylmethide triethylammonium (EuD4TEA) produces a TL emission yield that can be observed by the naked eye, it is still not sufficiently bright for use in smart sensor devices. Previous studies have shown that additional materials can be combined with EuD4TEA in order to improve the TL emission yield. In this paper, we discuss the effects of doping on EuD4TEA at different concentrations with a variety of materials on the TL emission yield and decay times. The dopants that were used in this study were nicotine, dibutyl phosphate (DBP), and magnesium. We also discuss both the effects of pH on EuD4TEA, and the doping effects on impact energy. For testing triboluminescent properties, we use a custom-built drop tower that generates triboluminescence by fracturing compounds through impact. Collected data is analyzed using specially written LabVIEW programs.

  16. No Evidence for a Relationship Between Hair Testosterone Concentrations and 2D:4D Ratio or Risk Taking

    Directory of Open Access Journals (Sweden)

    Richard Ronay

    2018-03-01

    Full Text Available Using a recently developed alternative assay procedure to measure hormone levels from hair samples, we examined the relationships between testosterone, cortisol, 2D:4D ratio, overconfidence and risk taking. A total of 162 (53 male participants provided a 3 cm sample of hair, a scanned image of their right and left hands from which we determined 2D:4D ratios, and completed measures of overconfidence and behavioral risk taking. While our sample size for males was less than ideal, our results revealed no evidence for a relationship between hair testosterone concentrations, 2D:4D ratios and risk taking. No relationships with overconfidence emerged. Partially consistent with the Dual Hormone Hypothesis, we did find evidence for the interacting effect of testosterone and cortisol on risk taking but only in men. Hair testosterone concentrations were positively related to risk taking when levels of hair cortisol concentrations were low, in men. Our results lend support to the suggestion that endogenous testosterone and 2D:4D ratio are unrelated and might then exert diverging activating vs. organizing effects on behavior. Comparing our results to those reported in the existing literature we speculate that behavioral correlates of testosterone such as direct effects on risk taking may be more sensitive to state-based fluctuations than baseline levels of testosterone.

  17. 2D:4D digit ratio predicts delay of gratification in preschoolers.

    Directory of Open Access Journals (Sweden)

    Sergio Da Silva

    Full Text Available We replicate the Stanford marshmallow experiment with a sample of 141 preschoolers and find a correlation between lack of self-control and 2D:4D digit ratio. Children with low 2D:4D digit ratio are less likely to delay gratification. Low 2D:4D digit ratio may indicate high fetal testosterone. If this hypothesis is true, our finding means high fetal testosterone children are less likely to delay gratification.

  18. A distinct DGAT with sn-3 acetyltransferase activity that synthesizes unusual, reduced-viscosity oils in Euonymus and transgenic seeds.

    Science.gov (United States)

    Durrett, Timothy P; McClosky, Daniel D; Tumaney, Ajay W; Elzinga, Dezi A; Ohlrogge, John; Pollard, Mike

    2010-05-18

    Endosperm and embryo tissues from the seeds of Euonymus alatus (Burning Bush) accumulate high levels of 3-acetyl-1,2-diacyl-sn-glycerols (acTAGs) as their major storage lipids. In contrast, the aril tissue surrounding the seed produces long-chain triacylglycerols (lcTAGs) typical of most other organisms. The presence of the sn-3 acetyl group imparts acTAGs with different physical and chemical properties, such as a 30% reduction in viscosity, compared to lcTAGs. Comparative transcriptome analysis of developing endosperm and aril tissues using pyrosequencing technology was performed to isolate the enzyme necessary for the synthesis of acTAGs. An uncharacterized membrane-bound O-acyltransferase (MBOAT) family member was the most abundant acyltransferase in the endosperm but was absent from the aril. Expression of this MBOAT in yeast resulted in the accumulation of acTAGs but not lcTAG; hence, the enzyme was named EaDAcT (Euonymus alatus diacylglycerol acetyltransferase). Yeast microsomes expressing EaDAcT possessed acetyl-CoA diacylglycerol acetyltransferase activity but lacked long-chain acyl-CoA diacylglycerol acyltransferase activity. Expression of EaDAcT under the control of a strong, seed-specific promoter in Arabidopsis resulted in the accumulation of acTAGs, up to 40 mol % of total TAG in the seed oil. These results demonstrate the utility of deep transcriptional profiling with multiple tissues as a gene discovery strategy for low-abundance proteins. They also show that EaDAcT is the acetyltransferase necessary and sufficient for the production of acTAGs in Euonymus seeds, and that this activity can be introduced into the seeds of other plants, allowing the evaluation of these unusual TAGs for biofuel and other applications.

  19. Distinct expression of alkaline phosphatase activity in epilimnetic bacteria: Implication for persistent DOC consumption in a P-limited reservoir

    Science.gov (United States)

    Tseng, Y.; Kao, S.; Shiah, F.

    2013-12-01

    In a P-deficient system, P availability usually controls the microbial activity and thus the ecosystem function. Thingstad et al. (1997) first addressed a 'Malfunctioning Microbial-loop' theory, which stated that low bacterial production (BP) caused by insufficient nutrient supply would result in DOC accumulation in an oligotrophic ecosystem. In this study we re-examined the theory by conducting seasonal patterns and correlations among soluble reactive phosphate (SRP) and DOC, microbial abundances (picocyanobacteria, bacteria, and heterotrophic nanoflagellate; HNF) and activities (primary production, bacterial production, and alkaline phosphatase activity; APA) coupled with enzyme-labeled fluorescence (ELF) assays on bacterioplankton in a subtropical reservoir sharing the common features, nitrate-replete and P-deficient, with most natural freshwater system during Oct 2007-Oct 2008. Persistently high APA was recorded during most of time, implying that the system was P-deficient. Size fractionated APA and ELF assay revealed that bacteria were the major APA contributor. However, significantly low epilimnion DOC was recorded during the stratified summer season accompanying with high BP and APA as well as high PP, implying that heterotrophic bacteria can well sustain in P-deficient system by utilizing DOP to rapidly lower down DOC under relatively high PP. Such findings oppose the 'Malfunctioning Microbial-loop' theory. On the other hand, strong epilimnetic DOC accumulation occurred in Oct 2007 under low light and low PP condition accompanying with high abundance of HNF, implying that HNF grazing may contribute to a certain degree of DOC accumulation. Correlation matrix supported our suggestions. This study testified the DOC dynamics in P-deficient ecosystem are tightly coupled with the source (PP and grazing) and sink (BP). We also suggested that in SRP-limited freshwater systems bacteria are capable of breaking down autochthonous DOC to reduce the chance of DOC

  20. Activated AKT/PKB signaling in C. elegans uncouples temporally distinct outputs of DAF-2/insulin-like signaling

    Directory of Open Access Journals (Sweden)

    Hanselman Keaton B

    2006-10-01

    Full Text Available Abstract Background In the nematode, Caenorhabditis elegans, a conserved insulin-like signaling pathway controls larval development, stress resistance and adult lifespan. AGE-1, a homolog of the p110 catalytic subunit of phosphoinositide 3-kinases (PI3K comprises the major known effector pathway downstream of the insulin receptor, DAF-2. Phospholipid products of AGE-1/PI3K activate AKT/PKB kinase signaling via PDK-1. AKT/PKB signaling antagonizes nuclear translocation of the DAF-16/FOXO transcription factor. Reduced AGE-1/PI3K signaling permits DAF-16 to direct dauer larval arrest and promote long lifespan in adult animals. In order to study the downstream effectors of AGE-1/PI3K signaling in C. elegans, we conducted a genetic screen for mutations that suppress the constitutive dauer arrest phenotype of age-1(mg109 animals. Results This report describes mutations recovered in a screen for suppressors of the constitutive dauer arrest (daf-C phenotype of age-1(mg109. Two mutations corresponded to alleles of daf-16. Two mutations were gain-of-function alleles in the genes, akt-1 and pdk-1, encoding phosphoinositide-dependent serine/threonine kinases. A fifth mutation, mg227, located on chromosome X, did not correspond to any known dauer genes, suggesting that mg227 may represent a new component of the insulin pathway. Genetic epistasis analysis by RNAi showed that reproductive development in age-1(mg109;akt-1(mg247 animals was dependent on the presence of pdk-1. Similarly, reproductive development in age-1(mg109;pdk-1(mg261 animals was dependent on akt-1. However, reproductive development in age-1(mg109; mg227 animals required only akt-1, and pdk-1 activity was dispensable in this background. Interestingly, while mg227 suppressed dauer arrest in age-1(mg109 animals, it enhanced the long lifespan phenotype. In contrast, akt-1(mg247 and pdk-1(mg261 did not affect lifespan or stress resistance, while both daf-16 alleles fully suppressed these

  1. Activated AKT/PKB signaling in C. elegans uncouples temporally distinct outputs of DAF-2/insulin-like signaling.

    Science.gov (United States)

    Gami, Minaxi S; Iser, Wendy B; Hanselman, Keaton B; Wolkow, Catherine A

    2006-10-04

    In the nematode, Caenorhabditis elegans, a conserved insulin-like signaling pathway controls larval development, stress resistance and adult lifespan. AGE-1, a homolog of the p110 catalytic subunit of phosphoinositide 3-kinases (PI3K) comprises the major known effector pathway downstream of the insulin receptor, DAF-2. Phospholipid products of AGE-1/PI3K activate AKT/PKB kinase signaling via PDK-1. AKT/PKB signaling antagonizes nuclear translocation of the DAF-16/FOXO transcription factor. Reduced AGE-1/PI3K signaling permits DAF-16 to direct dauer larval arrest and promote long lifespan in adult animals. In order to study the downstream effectors of AGE-1/PI3K signaling in C. elegans, we conducted a genetic screen for mutations that suppress the constitutive dauer arrest phenotype of age-1(mg109) animals. This report describes mutations recovered in a screen for suppressors of the constitutive dauer arrest (daf-C) phenotype of age-1(mg109). Two mutations corresponded to alleles of daf-16. Two mutations were gain-of-function alleles in the genes, akt-1 and pdk-1, encoding phosphoinositide-dependent serine/threonine kinases. A fifth mutation, mg227, located on chromosome X, did not correspond to any known dauer genes, suggesting that mg227 may represent a new component of the insulin pathway. Genetic epistasis analysis by RNAi showed that reproductive development in age-1(mg109);akt-1(mg247) animals was dependent on the presence of pdk-1. Similarly, reproductive development in age-1(mg109);pdk-1(mg261) animals was dependent on akt-1. However, reproductive development in age-1(mg109); mg227 animals required only akt-1, and pdk-1 activity was dispensable in this background. Interestingly, while mg227 suppressed dauer arrest in age-1(mg109) animals, it enhanced the long lifespan phenotype. In contrast, akt-1(mg247) and pdk-1(mg261) did not affect lifespan or stress resistance, while both daf-16 alleles fully suppressed these phenotypes. A screen for suppressors of PI3K

  2. The Relationship Between Digit Ratio (2D:4D) and Sexual Orientation in Men from China.

    Science.gov (United States)

    Xu, Yin; Zheng, Yong

    2016-04-01

    We examined the relationship between 2D:4D digit ratio and sexual orientation in men from China and analyzed the influences of the components used to assess sexual orientation and the criteria used to classify individuals as homosexual on this relationship. A total of 309 male and 110 female participants took part in a web-based survey. Our results showed that heterosexual men had a significantly lower 2D:4D than heterosexual women and exclusively homosexual men had a significantly higher left 2D:4D than heterosexual men whereas only exclusively homosexual men had a significantly higher right 2D:4D than heterosexual men when sexual orientation was assessed via sexual attraction. The left 2D:4D showed a significant positive correlation with sexual identity, sexual attraction, and sexual behavior, and the right 2D:4D showed a significant positive correlation with sexual attraction. The effect sizes for differences in 2D:4D between homosexual and heterosexual men varied according to criteria used to classify individuals as homosexual and sexual orientation components; the more stringent the criteria (scores closer to the homosexual category), the larger the effect sizes; further, sexual attraction yielded the largest effect size. There were no significant effects of age and latitude on Chinese 2D:4D. This study contributes to the current understanding of the relationship between 2D:4D and male sexual orientation.

  3. Distinct regions of the Phytophthora essential effector Avh238 determine its function in cell death activation and plant immunity suppression.

    Science.gov (United States)

    Yang, Bo; Wang, Qunqing; Jing, Maofeng; Guo, Baodian; Wu, Jiawei; Wang, Haonan; Wang, Yang; Lin, Long; Wang, Yan; Ye, Wenwu; Dong, Suomeng; Wang, Yuanchao

    2017-04-01

    Phytophthora pathogens secrete effectors to manipulate host innate immunity, thus facilitating infection. Among the RXLR effectors highly induced during Phytophthora sojae infection, Avh238 not only contributes to pathogen virulence but also triggers plant cell death. However, the detailed molecular basis of Avh238 functions remains largely unknown. We mapped the regions responsible for Avh238 functions in pathogen virulence and plant cell death induction using a strategy that combines investigation of natural variation and large-scale mutagenesis assays. The correlation between cellular localization and Avh238 functions was also evaluated. We found that the 79 th residue (histidine or leucine) of Avh238 determined its cell death-inducing activity, and that the 53 amino acids in its C-terminal region are responsible for promoting Phytophthora infection. Transient expression of Avh238 in Nicotiana benthamiana revealed that nuclear localization is essential for triggering cell death, while Avh238-mediated suppression of INF1-triggered cell death requires cytoplasmic localization. Our results demonstrate that a representative example of an essential Phytophthora RXLR effector can evolve to escape recognition by the host by mutating one nucleotide site, and can also retain plant immunosuppressive activity to enhance pathogen virulence in planta. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  4. The metabolically active subpopulation in Pseudomonas aeruginosa biofilms survives exposure to membrane-targeting antimicrobials via distinct molecular mechanisms

    DEFF Research Database (Denmark)

    Chiang, Wen-Chi; Pamp, Sünje Johanna; Nilsson, Martin

    2012-01-01

    encoding lipopolysaccharide modification enzymes, as well as on the mexAB-oprM, mexCD-oprJ, and muxABC-opmB genes encoding antimicrobial efflux pumps, but does not depend on the mexPQ-opmE efflux pump genes. Development of chlorhexidine-tolerant subpopulations was found to depend on the mexCD-oprJ genes......, but does not depend on the pmr, mexAB-oprM, mexPQ-opmE, or muxABC-opmB genes. Tolerance to SDS and EDTA in P. aeruginosa biofilms is linked to metabolically active cells, but does not depend on the pmr, mexAB, mexCD, mexPQ, or muxABC genes. Our data suggest that the active subpopulation in P. aeruginosa......-targeting compounds colistin, EDTA, SDS, and chlorhexidine resulted in the same spatial distribution of live and dead bacteria, we investigated whether tolerance to these compounds originated from the same molecular mechanisms. Development of colistin-tolerant subpopulations was found to depend on the pmr genes...

  5. Distinct activation phenotype of a highly conserved novel HLA-B57-restricted epitope during dengue virus infection.

    Science.gov (United States)

    Townsley, Elizabeth; Woda, Marcia; Thomas, Stephen J; Kalayanarooj, Siripen; Gibbons, Robert V; Nisalak, Ananda; Srikiatkhachorn, Anon; Green, Sharone; Stephens, Henry A F; Rothman, Alan L; Mathew, Anuja

    2014-01-01

    Variation in the sequence of T-cell epitopes between dengue virus (DENV) serotypes is believed to alter memory T-cell responses during second heterologous infections. We identified a highly conserved, novel, HLA-B57-restricted epitope on the DENV NS1 protein. We predicted higher frequencies of B57-NS1(26-34) -specific CD8(+) T cells in peripheral blood mononuclear cells from individuals undergoing secondary rather than primary DENV infection. However, high tetramer-positive T-cell frequencies during acute infection were seen in only one of nine subjects with secondary infection. B57-NS1(26-34) -specific and other DENV epitope-specific CD8(+) T cells, as well as total CD8(+) T cells, expressed an activated phenotype (CD69(+) and/or CD38(+)) during acute infection. In contrast, expression of CD71 was largely limited to DENV epitope-specific CD8(+) T cells. In vitro stimulation of cell lines indicated that CD71 expression was differentially sensitive to stimulation by homologous and heterologous variant peptides. CD71 may represent a useful marker of antigen-specific T-cell activation. © 2013 John Wiley & Sons Ltd.

  6. DMPD: Distinct functions of IRF-3 and IRF-7 in IFN-alpha gene regulation and controlof anti-tumor activity in primary macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16846591 Distinct functions of IRF-3 and IRF-7 in IFN-alpha gene regulation and con...cott J. Biochem Pharmacol. 2006 Nov 30;72(11):1469-76. Epub 2006 Jul 17. (.png) (.svg) (.html) (.csml) Show Distinct function...anti-tumor activity in primary macrophages. PubmedID 16846591 Title Distinct functions of IRF-3 and IRF-7 in

  7. The 11S Proteasomal Activator REGγ Impacts Polyglutamine-Expanded Androgen Receptor Aggregation and Motor Neuron Viability through Distinct Mechanisms

    Directory of Open Access Journals (Sweden)

    Jill M. Yersak

    2017-05-01

    Full Text Available Spinal and bulbar muscular atrophy (SBMA is caused by expression of a polyglutamine (polyQ-expanded androgen receptor (AR. The inefficient nuclear proteasomal degradation of the mutant AR results in the formation of nuclear inclusions containing amino-terminal fragments of the mutant AR. PA28γ (also referred to as REGγ is a nuclear 11S-proteasomal activator with limited proteasome activation capabilities compared to its cytoplasmic 11S (PA28α, PA28β counterparts. To clarify the role of REGγ in polyQ-expanded AR metabolism, we carried out genetic and biochemical studies in cell models of SBMA. Overexpression of REGγ in a PC12 cell model of SBMA increased polyQ-expanded AR aggregation and contributed to polyQ-expanded AR toxicity in the presence of dihydrotestosterone (DHT. These effects of REGγ were independent of its association with the proteasome and may be due, in part, to the decreased binding of polyQ-expanded AR by the E3 ubiquitin-ligase MDM2. Unlike its effects in PC12 cells, REGγ overexpression rescued transgenic SBMA motor neurons from DHT-induced toxicity in a proteasome binding-dependent manner, suggesting that the degradation of a specific 11S proteasome substrate or substrates promotes motor neuron viability. One potential substrate that we found to play a role in mutant AR toxicity is the splicing factor SC35. These studies reveal that, depending on the cellular context, two biological roles for REGγ impact cell viability in the face of polyQ-expanded AR; a proteasome binding-independent mechanism directly promotes mutant AR aggregation while a proteasome binding-dependent mechanism promotes cell viability. The balance between these functions likely determines REGγ effects on polyQ-expanded AR-expressing cells.

  8. Endothelial and Neuronal Nitric Oxide Activate Distinct Pathways on Sympathetic Neurotransmission in Rat Tail and Mesenteric Arteries.

    Directory of Open Access Journals (Sweden)

    Joana Beatriz Sousa

    Full Text Available Nitric oxide (NO seems to contribute to vascular homeostasis regulating neurotransmission. This work aimed at assessing the influence of NO from different sources and respective intracellular pathways on sympathetic neurotransmission, in two vascular beds. Electrically-evoked [3H]-noradrenaline release was assessed in rat mesenteric and tail arteries in the presence of NO donors or endothelial/neuronal nitric oxide synthase (NOS inhibitors. The influence of NO on adenosine-mediated effects was also studied using selective antagonists for adenosine receptors subtypes. Location of neuronal NOS (nNOS was investigated by immunohistochemistry (with specific antibodies for nNOS and for Schwann cells and Confocal Microscopy. Results indicated that: 1 in mesenteric arteries, noradrenaline release was reduced by NO donors and it was increased by nNOS inhibitors; the effect of NO donors was only abolished by the adenosine A1 receptors antagonist; 2 in tail arteries, noradrenaline release was increased by NO donors and it was reduced by eNOS inhibitors; adenosine receptors antagonists were devoid of effect; 3 confocal microscopy showed nNOS staining in adventitial cells, some co-localized with Schwann cells. nNOS staining and its co-localization with Schwann cells were significantly lower in tail compared to mesenteric arteries. In conclusion, in mesenteric arteries, nNOS, mainly located in Schwann cells, seems to be the main source of NO influencing perivascular sympathetic neurotransmission with an inhibitory effect, mediated by adenosine A1 receptors activation. Instead, in tail arteries endothelial NO seems to play a more relevant role and has a facilitatory effect, independent of adenosine receptors activation.

  9. Microsolvated Model for the Kinetics and Thermodynamics of Glycosidic Bond Dissociative Cleavage of Nucleoside D4G.

    Science.gov (United States)

    Jiang, Yang; Xue, Ying; Zeng, Yi

    2018-02-15

    Using the microsolvated model that involves explicit water molecules and implicit solvent in the optimization, two proposed dissociative hydrolysis mechanisms of 2',3'-didehydro-2',3'-dideoxyguanosine (d4G) have been first investigated by means of M06-2X(CPCM, water)/6-31++G(d,p) method. The glycosidic bond dissociation for the generation of the oxacarbenium ion intermediate is the rate-determining step (RDS). The subsequent nucleophilic water attack from different side of the oxacarbenium ion intermediate gives either the α-product [(2S,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-ol] or β-product [(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-ol] and is thus referred to as α-path (inversion) and β-path (retention). Two to five explicit water molecules (n = 2-5) are considered in the microsolvated model, and n = 3 or 4 is the smallest model capable of minimizing the activation energy for α-path and β-path, respectively. Our theoretical results suggest that α-path (n = 3) is more kinetically favorable with lower free energy barrier (RDS) of 27.7 kcal mol -1 , in contrast to that of 30.7 kcal mol -1 for the β-path (n = 4). The kinetic preference of the α-path is rationalized by NBO analysis. Whereas thte β-path is more thermodynamically favorable over the α-path, where the formation of β-product and α-product are exergonic and endergonic, respectively, providing theoretical support for the experimental observation that the β-cleavage product was the major one after sufficient reaction time. Comparisons of d4G with analogous cyclo-d4G and dG from kinetic free energy barriers and thermodynamic heterolytic dissociation energies were also carried out. Our kinetic and thermodynamic results manifest that the order of glycosidic bond stability should be d4G < cyclo-d4G < dG, which agrees well with the reported experimental stability order of d4G compounds and analogues and gives further understanding on the influence of 6-cyclopropylamino and unsaturated ribose to

  10. Distinct action of aranidipine and its active metabolite on renal arterioles, with special reference to renal protection.

    Science.gov (United States)

    Nakamura, A; Hayashi, K; Fujiwara, K; Ozawa, Y; Honda, M; Saruta, T

    2000-06-01

    Aranidipine, a newly developed calcium antagonist, possesses unique pharmacologic characteristics in that its metabolite (M-1) still has antihypertensive action. We examined the effects of both agents on renal microcirculation using the isolated perfused hydronephrotic rat kidney. During norepinephrine-induced constriction, the addition of aranidipine dilated both afferent and efferent arterioles in a dose-dependent manner; at 10(-6) M, 83 +/- 6% and 90 +/- 6% reversal, respectively. In contrast, its active metabolite exerted dilator action predominantly on the afferent arteriole (79 +/- 4% vs. 44 +/- 17% at 10(-6) M for afferent and efferent arterioles, respectively). We further examined the long-term (8 weeks) effect of these agents on the development of renal injury in salt-loaded subtotally nephrectomized spontaneously hypertensive rats. Both aranidipine and M-1 reduced blood pressure by a similar magnitude. The decreases in proteinuria were observed in the aranidipine-treated group at weeks 6, 8, and 10, whereas in the M-1 group, significant reduction was attained only at week 6. Histopathologic examination revealed that both treatments improved glomerular and arteriolar sclerosis. Glomerular sclerosis, however, was less pronounced in the aranidipine-treated group than in the M-1 group. In conclusion, aranidipine has dilator action on both arterioles, whereas M-1 caused predominant dilation of afferent arterioles. Such metabolic changes may constitute a determinant of efferent arteriolar action of the calcium antagonist.

  11. Activity-Dependent Ubiquitination of GluA1 Mediates a Distinct AMPAR Endocytosis and Sorting Pathway

    Science.gov (United States)

    Schwarz, Lindsay A.; Hall, Benjamin J.; Patrick, Gentry N.

    2010-01-01

    The accurate trafficking of AMPA receptors (AMPARs) to and from the synapse is a critical component of learning and memory in the brain, while dysfunction of AMPAR trafficking is hypothesized to be an underlying mechanism of Alzheimer’s disease. Previous work has shown that ubiquitination of integral membrane proteins is a common post-translational modification used to mediate endocytosis and endocytic sorting of surface proteins in eukaryotic cells. Here we report that mammalian AMPARs become ubiquitinated in response to their activation. Using a mutant of GluA1 that is unable to be ubiquitinated at lysines on its carboxy-terminus, we demonstrate that ubiquitination is required for internalization of surface AMPARs and their trafficking to the lysosome in response to the AMPAR agonist AMPA, but not for internalization of AMPARs in response to the NMDA receptor (NMDAR) agonist NMDA. Through over-expression or RNAi-mediated knockdown, we identify that a specific E3 ligase, Nedd4-1, is necessary for this process. Finally, we show that ubiquitination of GluA1 by Nedd4-1 becomes more prevalent as neurons mature. Together, these data show that ubiquitination of GluA1-containing AMPARs by Nedd4-1 mediates their endocytosis and trafficking to the lysosome. Furthermore, these results provide insight into how hippocampal neurons regulate AMPAR trafficking and degradation with high specificity in response to differing neuronal signaling cues, and suggest that changes to this pathway may occur as neurons mature. PMID:21148011

  12. Distinct symmetry and limited peptide refolding activity of the thermosomes from the acidothermophilic archaea Acidianus tengchongensis S5T

    International Nuclear Information System (INIS)

    Wang, Li; Hu, Zhong-jun; Luo, Yuan-ming; Huo, Yan-wu; Ma, Qing; He, Yong-zhi; Zhang, Yu-ying; Sun, Fei; Dong, Zhi-yang

    2010-01-01

    Recombinant thermosomes from the Acidianus tengchongensis strain S5 T were purified to homogeneity and assembled in vitro into homo-oligomers (rATcpnα or rATcpnβ) and hetero-oligomers (rATcpnαβ). The symmetries of these complexes were determined by electron microscopy and image analysis. The rATcpnα homo-oligomer was shown to possess 8-fold symmetry while both rATcpnβ and rATcpnαβ oligomers adopted 9-fold symmetry. rATcpnαβ oligomers were shown to contain the α and β subunits in a 1:2 ratio. All of the complexes prevented the irreversible inactivation of yeast alcohol dehydrogenase at 55 o C and completely prevented the formation of aggregates during thermal inactivation of citrate synthase at 45 o C. All rATcpn complexes showed trace ATP hydrolysis activity. Furthermore, rATcpnβ sequestered fully chemically denatured substrates (GFP and thermophilic malic dehydrogenase) in vitro without refolding them in an ATP-dependent manner. This property is similar to previously reported properties of chaperonins from Sulfolobus tokodaii and Sulfolobus acidocaldarius. These features are consistent with the slow growth rates of these species of archaea in their native environment.

  13. Activity-dependent ubiquitination of GluA1 mediates a distinct AMPA receptor endocytosis and sorting pathway.

    Science.gov (United States)

    Schwarz, Lindsay A; Hall, Benjamin J; Patrick, Gentry N

    2010-12-08

    The accurate trafficking of AMPA receptors (AMPARs) to and from the synapse is a critical component of learning and memory in the brain, whereas dysfunction of AMPAR trafficking is hypothesized to be an underlying mechanism of Alzheimer's disease. Previous work has shown that ubiquitination of integral membrane proteins is a common posttranslational modification used to mediate endocytosis and endocytic sorting of surface proteins in eukaryotic cells. Here we report that mammalian AMPARs become ubiquitinated in response to their activation. Using a mutant of GluA1 that is unable to be ubiquitinated at lysines on its C-terminus, we demonstrate that ubiquitination is required for internalization of surface AMPARs and their trafficking to the lysosome in response to the AMPAR agonist AMPA but not for internalization of AMPARs in response to the NMDA receptor agonist NMDA. Through overexpression or RNA interference-mediated knockdown, we identify that a specific E3 ligase, Nedd4-1 (neural-precursor cell-expressed developmentally downregulated gene 4-1), is necessary for this process. Finally, we show that ubiquitination of GluA1 by Nedd4-1 becomes more prevalent as neurons mature. Together, these data show that ubiquitination of GluA1-containing AMPARs by Nedd4-1 mediates their endocytosis and trafficking to the lysosome. Furthermore, these results provide insight into how hippocampal neurons regulate AMPAR trafficking and degradation with high specificity in response to differing neuronal signaling cues and suggest that changes to this pathway may occur as neurons mature.

  14. 2D:4D in Men Is Related to Aggressive Dominance but Not to Sociable Dominance

    NARCIS (Netherlands)

    van der Meij, L.; Almela, M.; Buunk, A.P.; Dubbs, S.; Salvador, A.

    2012-01-01

    It has been shown that a smaller ratio between the length of the second and fourth digit (2D:4D) is an indicator of the exposure to prenatal testosterone (T). This study measured the 2D:4D of men and assessed dominance as a personality trait to investigate indirectly if the exposure to prenatal T is

  15. 2D : 4D in Men Is Related to Aggressive Dominance but Not to Sociable Dominance

    NARCIS (Netherlands)

    van der Meij, Leander; Almela, Mercedes; Buunk, Abraham P.; Dubbs, Shelli; Salvador, Alicia

    2012-01-01

    It has been shown that a smaller ratio between the length of the second and fourth digit (2D:4D) is an indicator of the exposure to prenatal testosterone (T). This study measured the 2D:4D of men and assessed dominance as a personality trait to investigate indirectly if the exposure to prenatal T is

  16. 300 Area D4 Project 4th Quarter Fiscal Year 2006 Building Completion Report

    International Nuclear Information System (INIS)

    D. S. Smith

    2007-01-01

    This report documents the deactivation, decontamination, decommissioning, and demolition (D4) of nine buildings in the 300 Area of the Hanford Site. The D4 of these facilities included characterization, engineering, removal of hazardous and radiologically contaminated materials, equipment removal, utility disconnection, deactivation, decontamination, demolition of the structure, and stabilization or removal of the remaining slab and foundation, as appropriate

  17. 26 CFR 1.337(d)-4 - Taxable to tax-exempt.

    Science.gov (United States)

    2010-04-01

    ... deductions. The tax-exempt entity also must use this same reasonable method of allocation for each taxable... 26 Internal Revenue 4 2010-04-01 2010-04-01 false Taxable to tax-exempt. 1.337(d)-4 Section 1.337(d)-4 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX...

  18. Low and high gamma oscillations in rat ventral striatum have distinct relationships to behavior, reward, and spiking activity on a learned spatial decision task

    Directory of Open Access Journals (Sweden)

    Matthijs A A Van Der Meer

    2009-06-01

    Full Text Available Local field potential (LFP oscillations in the brain reflect organization thought to be important for perception, attention, movement, and memory. In the basal ganglia, including dorsal striatum, dysfunctional LFP states are associated with Parkinson’s disease, while in healthy subjects, dorsal striatal LFPs have been linked to decision-making processes. However, LFPs in ventral striatum have been less studied. We report that in rats running a spatial decision task, prominent gamma-50 (45-55 Hz and gamma-80 (70-85 Hz oscillations in ventral striatum had distinct relationships to behavior, task events, and spiking activity. Gamma-50 power increased sharply following reward delivery and before movement initiation, while in contrast, gamma-80 power ramped up gradually to reward locations. Gamma-50 power was low and contained little structure during early learning, but rapidly developed a stable pattern, while gamma-80 power was initially high before returning to a stable level within a similar timeframe. Putative fast-spiking interneurons (FSIs showed phase, firing rate, and coherence relationships with gamma-50 and gamma-80, indicating that the observed LFP patterns are locally relevant. Furthermore, in a number of FSIs such relationships were specific to gamma-50 or gamma-80, suggesting that partially distinct FSI populations mediate the effects of gamma-50 and gamma-80.

  19. Bartonella henselae trimeric autotransporter adhesin BadA expression interferes with effector translocation by the VirB/D4 type IV secretion system.

    Science.gov (United States)

    Lu, Yun-Yueh; Franz, Bettina; Truttmann, Matthias C; Riess, Tanja; Gay-Fraret, Jérémie; Faustmann, Marco; Kempf, Volkhard A J; Dehio, Christoph

    2013-05-01

    The Gram-negative, zoonotic pathogen Bartonella henselae is the aetiological agent of cat scratch disease, bacillary angiomatosis and peliosis hepatis in humans. Two pathogenicity factors of B. henselae - each displaying multiple functions in host cell interaction - have been characterized in greater detail: the trimeric autotransporter Bartonella adhesin A (BadA) and the type IV secretion system VirB/D4 (VirB/D4 T4SS). BadA mediates, e.g. binding to fibronectin (Fn), adherence to endothelial cells (ECs) and secretion of vascular endothelial growth factor (VEGF). VirB/D4 translocates several Bartonella effector proteins (Beps) into the cytoplasm of infected ECs, resulting, e.g. in uptake of bacterial aggregates via the invasome structure, inhibition of apoptosis and activation of a proangiogenic phenotype. Despite this knowledge of the individual activities of BadA or VirB/D4 it is unknown whether these major virulence factors affect each other in their specific activities. In this study, expression and function of BadA and VirB/D4 were analysed in a variety of clinical B. henselae isolates. Data revealed that most isolates have lost expression of either BadA or VirB/D4 during in vitro passages. However, the phenotypic effects of coexpression of both virulence factors was studied in one clinical isolate that was found to stably coexpress BadA and VirB/D4, as well as by ectopic expression of BadA in a strain expressing VirB/D4 but not BadA. BadA, which forms a dense layer on the bacterial surface, negatively affected VirB/D4-dependent Bep translocation and invasome formation by likely preventing close contact between the bacterial cell envelope and the host cell membrane. In contrast, BadA-dependent Fn binding, adhesion to ECs and VEGF secretion were not affected by a functional VirB/D4 T4SS. The obtained data imply that the essential virulence factors BadA and VirB/D4 are likely differentially expressed during different stages of the infection cycle of

  20. Modulating the Activity of the DLPFC and OFC Has Distinct Effects on Risk and Ambiguity Decision-Making: A tDCS Study.

    Science.gov (United States)

    Yang, Xiaolan; Gao, Mei; Shi, Jinchuan; Ye, Hang; Chen, Shu

    2017-01-01

    Human beings are constantly exposed to two types of uncertainty situations, risk and ambiguity. Neuroscientific studies suggest that the dorsolateral prefrontal cortex (DLPFC) and the orbital frontal cortex (OFC) play significant roles in human decision making under uncertainty. We applied the transcranial direct current stimulation (tDCS) device to modulate the activity of participants' DLPFC and OFC separately, comparing the causal relationships between people's behaviors and the activity of the corresponding brain cortex when confronted with situations of risk and ambiguity. Our experiment employed a pre-post design and a risk/ambiguity decision-making task, from which we could calculate the preferences via an estimation model. We found evidences that modulating the activity of the DLPFC using right anodal/left cathodal tDCS significantly enhanced the participants' preferences for risk, whereas modulating the activity of the OFC with right anodal/left cathodal tDCS significantly decreased the participants' preferences for ambiguity. The reverse effects were also observed in the reversed tDCS treatments on the two areas. Our results suggest that decision-making processes under risk and ambiguity are complicated and may be encoded in two distinct circuits in our brains as the DLPFC primarily impacts decisions under risk whereas the OFC affects ambiguity.

  1. Modulating the Activity of the DLPFC and OFC Has Distinct Effects on Risk and Ambiguity Decision-Making: A tDCS Study

    Directory of Open Access Journals (Sweden)

    Xiaolan Yang

    2017-08-01

    Full Text Available Human beings are constantly exposed to two types of uncertainty situations, risk and ambiguity. Neuroscientific studies suggest that the dorsolateral prefrontal cortex (DLPFC and the orbital frontal cortex (OFC play significant roles in human decision making under uncertainty. We applied the transcranial direct current stimulation (tDCS device to modulate the activity of participants’ DLPFC and OFC separately, comparing the causal relationships between people’s behaviors and the activity of the corresponding brain cortex when confronted with situations of risk and ambiguity. Our experiment employed a pre–post design and a risk/ambiguity decision-making task, from which we could calculate the preferences via an estimation model. We found evidences that modulating the activity of the DLPFC using right anodal/left cathodal tDCS significantly enhanced the participants’ preferences for risk, whereas modulating the activity of the OFC with right anodal/left cathodal tDCS significantly decreased the participants’ preferences for ambiguity. The reverse effects were also observed in the reversed tDCS treatments on the two areas. Our results suggest that decision-making processes under risk and ambiguity are complicated and may be encoded in two distinct circuits in our brains as the DLPFC primarily impacts decisions under risk whereas the OFC affects ambiguity.

  2. Distinct summer and winter bacterial communities in the active layer of Svalbard permafrost revealed by DNA- and RNA-based analyses

    Science.gov (United States)

    Schostag, Morten; Stibal, Marek; Jacobsen, Carsten S.; Bælum, Jacob; Taş, Neslihan; Elberling, Bo; Jansson, Janet K.; Semenchuk, Philipp; Priemé, Anders

    2015-01-01

    The active layer of soil overlaying permafrost in the Arctic is subjected to dramatic annual changes in temperature and soil chemistry, which likely affect bacterial activity and community structure. We studied seasonal variations in the bacterial community of active layer soil from Svalbard (78°N) by co-extracting DNA and RNA from 12 soil cores collected monthly over a year. PCR amplicons of 16S rRNA genes (DNA) and reverse transcribed transcripts (cDNA) were quantified and sequenced to test for the effect of low winter temperature and seasonal variation in concentration of easily degradable organic matter on the bacterial communities. The copy number of 16S rRNA genes and transcripts revealed no distinct seasonal changes indicating potential bacterial activity during winter despite soil temperatures well below −10°C. Multivariate statistical analysis of the bacterial diversity data (DNA and cDNA libraries) revealed a season-based clustering of the samples, and, e.g., the relative abundance of potentially active Cyanobacteria peaked in June and Alphaproteobacteria increased over the summer and then declined from October to November. The structure of the bulk (DNA-based) community was significantly correlated with pH and dissolved organic carbon, while the potentially active (RNA-based) community structure was not significantly correlated with any of the measured soil parameters. A large fraction of the 16S rRNA transcripts was assigned to nitrogen-fixing bacteria (up to 24% in June) and phototrophic organisms (up to 48% in June) illustrating the potential importance of nitrogen fixation in otherwise nitrogen poor Arctic ecosystems and of phototrophic bacterial activity on the soil surface. PMID:25983731

  3. Complete identification of E-selectin ligand activity on neutrophils reveals a dynamic interplay and distinct functions of PSGL-1, ESL-1 and CD44

    Science.gov (United States)

    Wild, Martin; Vestweber, Dietmar; Frenette, Paul S.

    2014-01-01

    SUMMARY The selectins and their ligands are required for leukocyte extravasation during inflammation. Several glycoproteins have been suggested to bind to E-selectin in vitro but the complete identification of its physiological ligands has remained elusive. Here, we show using gene- and RNA-targeted loss-of-function that E-selectin ligand-1 (ESL-1), PSGL-1 and CD44 encompass all endothelial selectin ligand activity on neutrophils. PSGL-1 plays a major role in the initial leukocyte capture, while ESL-1 is critical to convert initial tethers into steady slow rolling. CD44 controls rolling velocity and mediates E-selectin-dependent redistribution of PSGL-1 and L-selectin to a major pole on slowly rolling leukocytes through p38 signaling. These results suggest distinct and dynamic contributions of these three glycoproteins in selectin-mediated neutrophil adhesion and signaling. PMID:17442598

  4. Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci.

    Science.gov (United States)

    Smeets, Daniel; Markaki, Yolanda; Schmid, Volker J; Kraus, Felix; Tattermusch, Anna; Cerase, Andrea; Sterr, Michael; Fiedler, Susanne; Demmerle, Justin; Popken, Jens; Leonhardt, Heinrich; Brockdorff, Neil; Cremer, Thomas; Schermelleh, Lothar; Cremer, Marion

    2014-01-01

    A Xist RNA decorated Barr body is the structural hallmark of the compacted inactive X territory in female mammals. Using super-resolution three-dimensional structured illumination microscopy (3D-SIM) and quantitative image analysis, we compared its ultrastructure with active chromosome territories (CTs) in human and mouse somatic cells, and explored the spatio-temporal process of Barr body formation at onset of inactivation in early differentiating mouse embryonic stem cells (ESCs). We demonstrate that all CTs are composed of structurally linked chromatin domain clusters (CDCs). In active CTs the periphery of CDCs harbors low-density chromatin enriched with transcriptionally competent markers, called the perichromatin region (PR). The PR borders on a contiguous channel system, the interchromatin compartment (IC), which starts at nuclear pores and pervades CTs. We propose that the PR and macromolecular complexes in IC channels together form the transcriptionally permissive active nuclear compartment (ANC). The Barr body differs from active CTs by a partially collapsed ANC with CDCs coming significantly closer together, although a rudimentary IC channel system connected to nuclear pores is maintained. Distinct Xist RNA foci, closely adjacent to the nuclear matrix scaffold attachment factor-A (SAF-A) localize throughout Xi along the rudimentary ANC. In early differentiating ESCs initial Xist RNA spreading precedes Barr body formation, which occurs concurrent with the subsequent exclusion of RNA polymerase II (RNAP II). Induction of a transgenic autosomal Xist RNA in a male ESC triggers the formation of an 'autosomal Barr body' with less compacted chromatin and incomplete RNAP II exclusion. 3D-SIM provides experimental evidence for profound differences between the functional architecture of transcriptionally active CTs and the Barr body. Basic structural features of CT organization such as CDCs and IC channels are however still recognized, arguing against a uniform

  5. The D4Z4 macrosatellite repeat acts as a CTCF and A-type lamins-dependent insulator in facio-scapulo-humeral dystrophy.

    Directory of Open Access Journals (Sweden)

    Alexandre Ottaviani

    2009-02-01

    Full Text Available Both genetic and epigenetic alterations contribute to Facio-Scapulo-Humeral Dystrophy (FSHD, which is linked to the shortening of the array of D4Z4 repeats at the 4q35 locus. The consequence of this rearrangement remains enigmatic, but deletion of this 3.3-kb macrosatellite element might affect the expression of the FSHD-associated gene(s through position effect mechanisms. We investigated this hypothesis by creating a large collection of constructs carrying 1 to >11 D4Z4 repeats integrated into the human genome, either at random sites or proximal to a telomere, mimicking thereby the organization of the 4q35 locus. We show that D4Z4 acts as an insulator that interferes with enhancer-promoter communication and protects transgenes from position effect. This last property depends on both CTCF and A-type Lamins. We further demonstrate that both anti-silencing activity of D4Z4 and CTCF binding are lost upon multimerization of the repeat in cells from FSHD patients compared to control myoblasts from healthy individuals, suggesting that FSHD corresponds to a gain-of-function of CTCF at the residual D4Z4 repeats. We propose that contraction of the D4Z4 array contributes to FSHD physio-pathology by acting as a CTCF-dependent insulator in patients.

  6. Assessment of the 2D:4D ratio in aggression-related injuries in children attending a paediatric emergency department.

    Science.gov (United States)

    O'Briain, D E; Dawson, P H; Kelly, J C; Connolly, P

    2017-05-01

    The 2D:4D ratio is a sexually dimorphic trait. A lower ratio is correlated with sporting prowess, successful financial trading, risk taking behaviour, aggression, and aggression-related injuries, such as the fifth metacarpal fractures. We aimed to assess if the ratio correlates to skeletally immature patient aggression. Radiology reports were searched for the terms "5th metacarpal" or "boxer". Of 537 X-rays, 142 had fractures. The mechanism of injury was recorded in 102 patients, differentiating aggressive and non-aggressive injury groups. Bone age and chronological age were recorded. A clear male preponderance for aggression was identified with only 60% of non-aggressive injuries occurring in males compared to 95% in the aggression group (p aggression injuries were older chronologically (14.6 vs 12.7, p Aggression injuries occur at an older age and are more common in males. In the female cohort, there was a distinct difference in digit ratio.

  7. Auxin-activated NADH oxidase activity of soybean plasma membranes is distinct from the constitutive plasma membrane NADH oxidase and exhibits prion-like properties

    Science.gov (United States)

    Morre, D. James; Morre, Dorothy M.; Ternes, Philipp

    2003-01-01

    The hormone-stimulated and growth-related cell surface hydroquinone (NADH) oxidase activity of etiolated hypocotyls of soybeans oscillates with a period of about 24 min or 60 times per 24-h day. Plasma membranes of soybean hypocotyls contain two such NADH oxidase activities that have been resolved by purification on concanavalin A columns. One in the apparent molecular weight range of 14-17 kDa is stimulated by the auxin herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). The other is larger and unaffected by 2,4-D. The 2,4-D-stimulated activity absolutely requires 2,4-D for activity and exhibits a period length of about 24 min. Also exhibiting 24-min oscillations is the rate of cell enlargement induced by the addition of 2,4-D or the natural auxin indole-3-acetic acid (IAA). Immediately following 2,4-D or IAA addition, a very complex pattern of oscillations is frequently observed. However, after several hours a dominant 24-min period emerges at the expense of the constitutive activity. A recruitment process analogous to that exhibited by prions is postulated to explain this behavior.

  8. Facts and Misconceptions about 2D:4D, Social and Risk Preferences

    Science.gov (United States)

    Alonso, Judit; Di Paolo, Roberto; Ponti, Giovanni; Sartarelli, Marcello

    2018-01-01

    We study how the ratio between the length of the second and fourth digit (2D:4D) correlates with choices in social and risk preferences elicitation tasks by building a large dataset from five experimental projects with more than 800 subjects. Our results confirm the recent literature that downplays the link between 2D:4D and many domains of economic interest, such as social and risk preferences. As for the former, we find that social preferences are significantly lower when 2D:4D is above the median value only for subjects with low cognitive ability. As for the latter, we find that a high 2D:4D is not correlated with the frequency of subjects' risky choices. PMID:29487510

  9. Synthesis and crystal structure of lithium beryllium deuteride Li2BeD4.

    Science.gov (United States)

    Bulychev, Boris M; Shpanchenko, Roman V; Antipov, Evgeny V; Sheptyakov, Denis V; Bushmeleva, Svetlana N; Balagurov, Anatoly M

    2004-10-04

    Single-phase ternary deuteride Li(2)BeD(4) was synthesized by a high-pressure high-temperature technique from LiD and BeD(2). The crystal structure of Li(2)BeD(4) was solved from X-ray and neutron powder diffraction data. The compound crystallizes in the monoclinic space group P2(1)/c with lattice parameters a = 7.06228(9) A, b = 8.3378(1) A, c = 8.3465(1) A, beta =93.577(1) degrees, and Z = 8. Its structure contains isolated BeD(4) tetrahedra and Li atoms that are located in the structure interstices. Li(2)BeD(4) does not undergo any structural phase transitions at temperatures down to 8 K.

  10. Generating functional for Donaldson invariants and operator algebra in topological D=4 Yang-Mills theory

    International Nuclear Information System (INIS)

    Johansen, A.A.

    1992-01-01

    It is shown, that under the certain constraints the generating functional for the Donaldson invariants in the D=4 topological Yang-Mills theory can be interpreted as a partition function for the renormalizable theory. 20 refs

  11. Low 2D:4D values are associated with video game addiction.

    Science.gov (United States)

    Kornhuber, Johannes; Zenses, Eva-Maria; Lenz, Bernd; Stoessel, Christina; Bouna-Pyrrou, Polyxeni; Rehbein, Florian; Kliem, Sören; Mößle, Thomas

    2013-01-01

    Androgen-dependent signaling regulates the growth of the fingers on the human hand during embryogenesis. A higher androgen load results in lower 2D:4D (second digit to fourth digit) ratio values. Prenatal androgen exposure also impacts brain development. 2D:4D values are usually lower in males and are viewed as a proxy of male brain organization. Here, we quantified video gaming behavior in young males. We found lower mean 2D:4D values in subjects who were classified according to the CSAS-II as having at-risk/addicted behavior (n = 27) compared with individuals with unproblematic video gaming behavior (n = 27). Thus, prenatal androgen exposure and a hyper-male brain organization, as represented by low 2D:4D values, are associated with problematic video gaming behavior. These results may be used to improve the diagnosis, prediction, and prevention of video game addiction.

  12. Low 2D:4D values are associated with video game addiction.

    Directory of Open Access Journals (Sweden)

    Johannes Kornhuber

    Full Text Available Androgen-dependent signaling regulates the growth of the fingers on the human hand during embryogenesis. A higher androgen load results in lower 2D:4D (second digit to fourth digit ratio values. Prenatal androgen exposure also impacts brain development. 2D:4D values are usually lower in males and are viewed as a proxy of male brain organization. Here, we quantified video gaming behavior in young males. We found lower mean 2D:4D values in subjects who were classified according to the CSAS-II as having at-risk/addicted behavior (n = 27 compared with individuals with unproblematic video gaming behavior (n = 27. Thus, prenatal androgen exposure and a hyper-male brain organization, as represented by low 2D:4D values, are associated with problematic video gaming behavior. These results may be used to improve the diagnosis, prediction, and prevention of video game addiction.

  13. Endogenous leukotriene D4 formation during anaphylactic shock in the guinea pig

    International Nuclear Information System (INIS)

    Keppler, A.; Oerning, L.; Bernstroem, K.; Hammarstroem, S.

    1987-01-01

    Experiments on the metabolism and excretion of i.v. administered selectively labeled [ 3 H 8 ]leukotriene C 4 in bile duct-cannulated guinea pigs indicated predominantly biliary excretion of tritium. The major leukotriene metabolite in bile was identified as leukotriene D 4 . By monitoring leukotriene excretion radioimmunochromatographically, it was shown that guinea pigs suffering from anaphylactic shock produce leukotriene D 4 endogenously. Immunological challenge of animals sensitized to ovalbumin was accompanied by an increase of biliary leukotriene D 4 concentrations from 10 +/- 1 to 86 +/- 10 nM. When considering that bile flow was decreased to about half after challenge, the excretion rate of leukotriene D 4 in bile increased from 0.88 +/- 0.16 before 3.18 +/- 0.38 pmol x min -1 x kg -1 after challenge. It is concluded that systemic anaphylaxis in the guinea pig is associated with endogenous generation of leukotriene C 4

  14. The 3d4-3d34p transitions of triply ionized manganese (Mn IV)

    International Nuclear Information System (INIS)

    Tchang-Brillet, W.Ue.L.; Artru, M.C.; Wyart, J.F.

    1986-01-01

    The analysis of Mn IV is extended in the wavelength range 473-847 A. A total of 600 classified lines are given, of which 372 are newly observed. All of them are due to 3d 4 -3d 3 4p transitions. Their classification and the identification of 59 new levels are supported by the parametric studies of the 3d 4 and 3d 3 4p configurations. The ground configuration 3d 4 is calculated by taking into account the effective magnetic interactions which improve by an order of magnitude the theoretical fine structure of the quintet and triplet terms. The analysis was guided by the prediction of relative line strengths in intermediate coupling. Calculated energies and LS composition are given for all levels of the configuration, 3d 4 and 3d 3 4p. (orig).

  15. Diverse Brain Myeloid Expression Profiles Reveal Distinct Microglial Activation States and Aspects of Alzheimer’s Disease Not Evident in Mouse Models

    Directory of Open Access Journals (Sweden)

    Brad A. Friedman

    2018-01-01

    Full Text Available Microglia, the CNS-resident immune cells, play important roles in disease, but the spectrum of their possible activation states is not well understood. We derived co-regulated gene modules from transcriptional profiles of CNS myeloid cells of diverse mouse models, including new tauopathy model datasets. Using these modules to interpret single-cell data from an Alzheimer’s disease (AD model, we identified microglial subsets—distinct from previously reported “disease-associated microglia”—expressing interferon-related or proliferation modules. We then analyzed whole-tissue RNA profiles from human neurodegenerative diseases, including a new AD dataset. Correcting for altered cellular composition of AD tissue, we observed elevated expression of the neurodegeneration-related modules, but also modules not implicated using expression profiles from mouse models alone. We provide a searchable, interactive database for exploring gene expression in all these datasets (http://research-pub.gene.com/BrainMyeloidLandscape. Understanding the dimensions of CNS myeloid cell activation in human disease may reveal opportunities for therapeutic intervention.

  16. Hadza hunter-gatherer men do not have more masculine digit ratios (2D:4D).

    Science.gov (United States)

    Apicella, Coren L; Tobolsky, Victoria A; Marlowe, Frank W; Miller, Kathleen W

    2016-02-01

    The ratio between the length of the second and the length of the fourth digit (2D:4D) is sexually dimorphic such that males of many species possess a lower ratio than females, particularly in the right hand. Still, men and women often exhibit overlapping 2D:4D ranges and the ratio is highly variable between populations. In order to further explore populational variability, we chose to analyze 2D:4D in the Hadza, a population of hunter-gatherers living in Tanzania. Data were collected separately by two researchers over the course of three years (1998, 2001, 2006) from 152 adult participants (male: n = 76, female: n = 76). Independent samples t-tests were used to explore sex differences, paired samples t-tests were used to explore directional effects within each sex, and linear regression and one-way ANOVA were used to test possible age effects. In none of the years, or pooled (n = 152), did we find evidence that adult men have a lower 2D:4D than adult women. If anything, the data suggest that women in this population have a significantly lower right hand 2D:4D than men (P < 0.001, d = 0.57). In contrast, left hand 2D:4D did not exhibit a sex difference (P = 0.862, d = 0.03). These findings challenge the current view that lower 2D:4D in men is a uniform characteristic of our species. Cross-populational variance in 2D:4D may be related to known patterns of hormonal variation resulting from both genetic and environmental mechanisms, though this relationship merits further investigation. © 2015 Wiley Periodicals, Inc.

  17. Wess-Zumino and super Yang-Mills theories in D=4 integral superspace

    Science.gov (United States)

    Castellani, L.; Catenacci, R.; Grassi, P. A.

    2018-05-01

    We reconstruct the action of N = 1 , D = 4 Wess-Zumino and N = 1 , 2 , D = 4 super-Yang-Mills theories, using integral top forms on the supermanifold M^{(.4|4)} . Choosing different Picture Changing Operators, we show the equivalence of their rheonomic and superspace actions. The corresponding supergeometry and integration theory are discussed in detail. This formalism is an efficient tool for building supersymmetric models in a geometrical framework.

  18. Digit ratio (2D:4D) in primary brain tumor patients: A case-control study.

    Science.gov (United States)

    Bunevicius, Adomas; Tamasauskas, Sarunas; Deltuva, Vytenis Pranas; Tamasauskas, Arimantas; Sliauzys, Albertas; Bunevicius, Robertas

    2016-12-01

    The second-to-fourth digit ratio (2D:4D) reflects prenatal estrogen and testosterone exposure, and is established in utero. Sex steroids are implicated in development and progression of primary brain tumors. To investigate whether there is a link between 2D:4D ratio and primary brain tumors, and age at presentation. Digital images of the right and left palms of 85 primary brain tumor patients (age 56.96±13.68years; 71% women) and 106 (age 54.31±13.68years; 68% women) gender and age matched controls were obtained. The most common brain tumor diagnoses were meningioma (41%), glioblastoma (20%) and pituitary adenoma (16%). Right and left 2D:4D ratios, and right minus left 2D:4D (D r-l ) were compared between patients and controls, and were correlated with age. Right and left 2D:4D ratios were significantly lower in primary brain tumor patients relative to controls (t=-4.28, pbrain tumor patients and controls (p=0.27). In meningioma and glioma patients, age at presentation correlated negatively with left 2D:4D ratio (rho=-0.42, p=0.01 and rho=-0.36, p=0.02, respectively) and positively with D r-l (rho=0.45, p=0.009 and rho=0.65, p=0.04, respectively). Right and left hand 2D:4D ratios are lower in primary brain tumor patients relative to healthy individuals suggesting greater prenatal testosterone and lower prenatal estrogen exposure in brain tumor patients. Greater age at presentation is associated with greater D r-l and with lower left 2D:4D ratio of meningioma and glioma patients. Due to small sample size our results should be considered preliminary and interpreted with caution. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Quantum Distinction: Quantum Distinctiones!

    OpenAIRE

    Zeps, Dainis

    2009-01-01

    10 pages; How many distinctions, in Latin, quantum distinctiones. We suggest approach of anthropic principle based on anthropic reference system which should be applied equally both in theoretical physics and in mathematics. We come to principle that within reference system of life subject of mathematics (that of thinking) should be equated with subject of physics (that of nature). For this reason we enter notions of series of distinctions, quantum distinction, and argue that quantum distinct...

  20. cAMP response element binding protein (CREB activates transcription via two distinct genetic elements of the human glucose-6-phosphatase gene

    Directory of Open Access Journals (Sweden)

    Stefano Luisa

    2005-01-01

    Full Text Available Abstract Background The enzyme glucose-6-phosphatase catalyzes the dephosphorylation of glucose-6-phosphatase to glucose, the final step in the gluconeogenic and glycogenolytic pathways. Expression of the glucose-6-phosphatase gene is induced by glucocorticoids and elevated levels of intracellular cAMP. The effect of cAMP in regulating glucose-6-phosphatase gene transcription was corroborated by the identification of two genetic motifs CRE1 and CRE2 in the human and murine glucose-6-phosphatase gene promoter that resemble cAMP response elements (CRE. Results The cAMP response element is a point of convergence for many extracellular and intracellular signals, including cAMP, calcium, and neurotrophins. The major CRE binding protein CREB, a member of the basic region leucine zipper (bZIP family of transcription factors, requires phosphorylation to become a biologically active transcriptional activator. Since unphosphorylated CREB is transcriptionally silent simple overexpression studies cannot be performed to test the biological role of CRE-like sequences of the glucose-6-phosphatase gene. The use of a constitutively active CREB2/CREB fusion protein allowed us to uncouple the investigation of target genes of CREB from the variety of signaling pathways that lead to an activation of CREB. Here, we show that this constitutively active CREB2/CREB fusion protein strikingly enhanced reporter gene transcription mediated by either CRE1 or CRE2 derived from the glucose-6-phosphatase gene. Likewise, reporter gene transcription was enhanced following expression of the catalytic subunit of cAMP-dependent protein kinase (PKA in the nucleus of transfected cells. In contrast, activating transcription factor 2 (ATF2, known to compete with CREB for binding to the canonical CRE sequence 5'-TGACGTCA-3', did not transactivate reporter genes containing CRE1, CRE2, or both CREs derived from the glucose-6-phosphatase gene. Conclusions Using a constitutively active CREB2

  1. Dopamine D4 receptor polymorphism modulates cue-elicited heroin craving in Chinese.

    Science.gov (United States)

    Shao, Chunhong; Li, Yifeng; Jiang, Kaida; Zhang, Dandan; Xu, Yifeng; Lin, Ling; Wang, Qiuying; Zhao, Min; Jin, Li

    2006-06-01

    Subjective craving, which contributes to the continuation of drug use in active abuser and the occurrence of relapse in detoxified abusers, is considered to be a central phenomenon in addiction. Dopamine pathway has been implicated in the mechanism underlying the cue-elicited craving for a variety of addictive substances. The objective of this study was to test the hypothesis that heroin addicts carrying D4 dopamine receptor gene (DRD4) variable number tandem repeat (VNTR) long type allele would have higher craving after exposure to a heroin-related cue. Craving was induced by a series of exposure to neutral and heroin-related cue and were assessed in a cohort of Chinese heroin abusers (n=420) recruited from the Voluntary Drug Dependence Treatment Center at Shanghai. Significantly stronger cue-elicited heroin craving was found in individuals carrying DRD4 VNTR long type allele than the non-carriers (F=31.040, pcue-elicited craving in heroin dependence, indicating DRD4 VNTR represents one of potential genetic risk factors for cue-induced craving.

  2. Hypersexual, Sexually Compulsive, or Just Highly Sexually Active? Investigating Three Distinct Groups of Gay and Bisexual Men and Their Profiles of HIV-Related Sexual Risk

    Science.gov (United States)

    Rendina, H. Jonathon; Ventuneac, Ana; Moody, Raymond L.; Grov, Christian

    2015-01-01

    Emerging research supports the notion that sexual compulsivity (SC) and hypersexual disorder (HD) among gay and bisexual men (GBM) might be conceptualized as comprising three groups—Neither SC nor HD; SC only, and Both SC and HD—that capture distinct levels of severity across the SC/HD continuum. We examined data from 370 highly sexually active GBM to assess how the three groups compare across a range of risk factors for HIV infection. Comparisons focused on psychosexual measures—temptation for condomless anal sex (CAS), self-efficacy for avoiding CAS, sexual excitation and inhibition—as well as reports of actual sexual behavior. Nearly half (48.9 %) of this highly sexually active sample was classified as Neither SC nor HD, 30 % as SC Only, and 21.1 % as Both SC and HD. While we found no significant differences between the three groups on reported number of male partners, anal sex acts, or anal sex acts with serodiscordant partners, the Both SC and HD group reported higher numbers of CAS acts and CAS acts with serodiscordant partners and also had a higher proportion of their anal sex acts without condoms compared to the SC Only group. Our findings support the validity of a three-group classification system of SC/HD severity in differentiating psychosexual and HIV-related sexual risk behavior outcomes in a sample of GBM who report similarly high levels of sexual activity. Notwithstanding the need for sex positive HIV prevention programs, interventions that attempt to help Both SC and HD men deal with distress and address their psychosexual needs specifically may derive HIV prevention benefits. PMID:25750052

  3. Antigen presentation by resting B cells. Radiosensitivity of the antigen-presentation function and two distinct pathways of T cell activation

    International Nuclear Information System (INIS)

    Ashwell, J.D.; DeFranco, A.L.; Paul, W.E.; Schwartz, R.H.

    1984-01-01

    In this report we have examined the ability of small resting B cells to act as antigen-presenting cells (APC) to antigen-specific MHC-restricted T cells as assessed by either T cell proliferation or T cell-dependent B cell stimulation. We found that 10 of 14 in vitro antigen-specific MHC-restricted T cell clones and lines and three of four T cell hybridomas could be induced to either proliferate or secrete IL-2 in the presence of lightly irradiated (1,000 rads) purified B cells and the appropriate foreign antigen. All T cell lines and hybridomas were stimulated to proliferate or make IL-2 by macrophage- and dendritic cell-enriched populations and all T cells tested except one hybridoma caused B cell activation when stimulated with B cells as APC. Furthermore, lightly irradiated, highly purified syngeneic B cells were as potent a source of APC for inducing B cell activation as were low density dendritic and macrophage-enriched cells. Lymph node T cells freshly taken from antigen-primed animals were also found to proliferate when cultured with purified B cells and the appropriate antigen. This APC function was easily measured when the cells were irradiated with 1,000 rads, but was greatly diminished or absent when they were irradiated with 3,300 rads. In addition, this radiosensitivity allowed us to easily distinguish B cell antigen presentation from presentation by the dendritic cell and macrophage, as the latter was resistant to 3,300 rads. Finally, one T cell clone that failed to proliferate when B cells were used as APC was able to recruit allogeneic B cells to proliferate in the presence of syngeneic B cells and the appropriate antigen. This result suggests that there are at least two distinct pathways of activation in T cells, one that leads to T cell proliferation and one that leads to the secretion of B cell recruitment factor(s)

  4. Adenoviral gene transfer of PLD1-D4 enhances insulin sensitivity in mice by disrupting phospholipase D1 interaction with PED/PEA-15.

    Directory of Open Access Journals (Sweden)

    Angela Cassese

    Full Text Available Over-expression of phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (PED/PEA-15 causes insulin resistance by interacting with the D4 domain of phospholipase D1 (PLD1. Indeed, the disruption of this association restores insulin sensitivity in cultured cells over-expressing PED/PEA-15. Whether the displacement of PLD1 from PED/PEA-15 improves insulin sensitivity in vivo has not been explored yet. In this work we show that treatment with a recombinant adenoviral vector containing the human D4 cDNA (Ad-D4 restores normal glucose homeostasis in transgenic mice overexpressing PED/PEA-15 (Tg ped/pea-15 by improving both insulin sensitivity and secretion. In skeletal muscle of these mice, D4 over-expression inhibited PED/PEA-15-PLD1 interaction, decreased Protein Kinase C alpha activation and restored insulin induced Protein Kinase C zeta activation, leading to amelioration of insulin-dependent glucose uptake. Interestingly, Ad-D4 administration improved insulin sensitivity also in high-fat diet treated obese C57Bl/6 mice. We conclude that PED/PEA-15-PLD1 interaction may represent a novel target for interventions aiming at improving glucose tolerance.

  5. Dopamine D4 receptor stimulation contributes to novel object recognition: Relevance to cognitive impairment in schizophrenia.

    Science.gov (United States)

    Miyauchi, Masanori; Neugebauer, Nichole M; Meltzer, Herbert Y

    2017-04-01

    Several atypical antipsychotic drugs (APDs) have high affinity for the dopamine (DA) D 4 receptor, but the relevance to the efficacy for the treatment of cognitive impairment associated with schizophrenia (CIAS) is poorly understood. The aim of this study was to investigate the effects of D 4 receptor stimulation or blockade on novel object recognition (NOR) in normal rats and on the sub-chronic phencyclidine (PCP)-induced novel object recognition deficit. The effect of the D 4 agonist, PD168077, and the D 4 antagonist, L-745,870, were studied alone, and in combination with clozapine and lurasidone. In normal rats, L-745,870 impaired novel object recognition, whereas PD168077 had no effect. PD168077 acutely reversed the sub-chronic phencyclidine-induced novel object recognition deficit. Co-administration of a sub-effective dose (SED) of PD168077 with a sub-effective dose of lurasidone also reversed this deficit, but a sub-effective dose of PD168077 with a sub-effective dose of clozapine, a more potent D 4 antagonist than lurasidone, did not reverse the sub-chronic phencyclidine-induced novel object recognition deficit. At a dose that did not induce a novel object recognition deficit, L-745,870 blocked the ability of clozapine, but not lurasidone, to reverse the novel object recognition deficit. D 4 receptor agonism has a beneficial effect on novel object recognition in sub-chronic PCP-treated rats and augments the cognitive enhancing efficacy of an atypical antipsychotic drug that lacks affinity for the D 4 receptor, lurasidone.

  6. Risk Preferences and Predictions about Others: No Association with 2D:4D Ratio

    Directory of Open Access Journals (Sweden)

    Katharina Lima de Miranda

    2018-02-01

    Full Text Available Prenatal androgen exposure affects the brain development of the fetus which may facilitate certain behaviors and decision patterns in the later life. The ratio between the lengths of second and the fourth fingers (2D:4D is a negative biomarker of the ratio between prenatal androgen and estrogen exposure and men typically have lower ratios than women. In line with the typical findings suggesting that women are more risk averse than men, several studies have also shown negative relationships between 2D:4D and risk taking although the evidence is not conclusive. Previous studies have also reported that both men and women believe women are more risk averse than men. In the current study, we re-test the relationship between 2D:4D and risk preferences in a German student sample and also investigate whether the 2D:4D ratio is associated with people’s perceptions about others’ risk preferences. Following an incentivized risk elicitation task, we asked all participants their predictions about (i others’ responses (without sex specification, (ii men’s responses, and (iii women’s responses; then measured their 2D:4D ratios. In line with the previous findings, female participants in our sample were more risk averse. While both men and women underestimated other participants’ (non sex-specific and women’s risky decisions on average, their predictions about men were accurate. We also found evidence for the false consensus effect, as risky choices are positively correlated with predictions about other participants’ risky choices. The 2D:4D ratio was not directly associated either with risk preferences or the predictions of other participants’ choices. An unexpected finding was that women with mid-range levels of 2D:4D estimated significantly larger sex differences in participants’ decisions. This finding needs further testing in future studies.

  7. Risk Preferences and Predictions about Others: No Association with 2D:4D Ratio

    Science.gov (United States)

    Lima de Miranda, Katharina; Neyse, Levent; Schmidt, Ulrich

    2018-01-01

    Prenatal androgen exposure affects the brain development of the fetus which may facilitate certain behaviors and decision patterns in the later life. The ratio between the lengths of second and the fourth fingers (2D:4D) is a negative biomarker of the ratio between prenatal androgen and estrogen exposure and men typically have lower ratios than women. In line with the typical findings suggesting that women are more risk averse than men, several studies have also shown negative relationships between 2D:4D and risk taking although the evidence is not conclusive. Previous studies have also reported that both men and women believe women are more risk averse than men. In the current study, we re-test the relationship between 2D:4D and risk preferences in a German student sample and also investigate whether the 2D:4D ratio is associated with people’s perceptions about others’ risk preferences. Following an incentivized risk elicitation task, we asked all participants their predictions about (i) others’ responses (without sex specification), (ii) men’s responses, and (iii) women’s responses; then measured their 2D:4D ratios. In line with the previous findings, female participants in our sample were more risk averse. While both men and women underestimated other participants’ (non sex-specific) and women’s risky decisions on average, their predictions about men were accurate. We also found evidence for the false consensus effect, as risky choices are positively correlated with predictions about other participants’ risky choices. The 2D:4D ratio was not directly associated either with risk preferences or the predictions of other participants’ choices. An unexpected finding was that women with mid-range levels of 2D:4D estimated significantly larger sex differences in participants’ decisions. This finding needs further testing in future studies. PMID:29472846

  8. Finger length ratio (2D:4D) in adults with gender identity disorder.

    Science.gov (United States)

    Kraemer, Bernd; Noll, Thomas; Delsignore, Aba; Milos, Gabriella; Schnyder, Ulrich; Hepp, Urs

    2009-06-01

    From early childhood, gender identity and the 2nd to 4th finger length ratio (2D:4D) are discriminative characteristics between sexes. Both the human brain and 2D:4D may be influenced by prenatal testosterone levels. This calls for an examination of 2D:4D in patients with gender identity disorder (GID) to study the possible influence of prenatal testosterone on gender identity. Until now, the only study carried out on this issue suggests lower prenatal testosterone levels in right-handed male-to-female GID patients (MtF). We compared 2D:4D of 56 GID patients (39 MtF; 17 female-to-male GID patients, FtM) with data from a control sample of 176 men and 190 women. Bivariate group comparisons showed that right hand 2D:4D in MtF was significantly higher (feminized) than in male controls, but similar to female controls. The comparison of 2D:4D ratios of biological women revealed significantly higher (feminized) values for right hands of right handed FtM. Analysis of variance confirmed significant effects for sex and for gender identity on 2D:4D ratios but not for sexual orientation or for the interaction among variables. Our results indirectly point to the possibility of a weak influence of reduced prenatal testosterone as an etiological factor in the multifactorially influenced development of MtF GID. The development of FtM GID seems even more unlikely to be notably influenced by prenatal testosterone.

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

    Science.gov (United States)

    Yakovleva, Lyudmila; Shuman, Stewart

    2012-08-01

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

  10. Three Fusarium oxysporum mitogen-activated protein kinases (MAPKs) have distinct and complementary roles in stress adaptation and cross-kingdom pathogenicity.

    Science.gov (United States)

    Segorbe, David; Di Pietro, Antonio; Pérez-Nadales, Elena; Turrà, David

    2017-09-01

    Mitogen-activated protein kinase (MAPK) cascades mediate cellular responses to environmental signals. Previous studies in the fungal pathogen Fusarium oxysporum have revealed a crucial role of Fmk1, the MAPK orthologous to Saccharomyces cerevisiae Fus3/Kss1, in vegetative hyphal fusion and plant infection. Here, we genetically dissected the individual and combined contributions of the three MAPKs Fmk1, Mpk1 and Hog1 in the regulation of development, stress response and virulence of F. oxysporum on plant and animal hosts. Mutants lacking Fmk1 or Mpk1 were affected in reactive oxygen species (ROS) homeostasis and impaired in hyphal fusion and aggregation. Loss of Mpk1 also led to increased sensitivity to cell wall and heat stress, which was exacerbated by simultaneous inactivation of Fmk1, suggesting that both MAPKs contribute to cellular adaptation to high temperature, a prerequisite for mammalian pathogens. Deletion of Hog1 caused increased sensitivity to hyperosmotic stress and resulted in partial rescue of the restricted colony growth phenotype of the mpk1Δ mutant. Infection assays on tomato plants and the invertebrate animal host Galleria mellonella revealed distinct and additive contributions of the different MAPKs to virulence. Our results indicate that positive and negative cross-talk between the three MAPK pathways regulates stress adaptation, development and virulence in the cross-kingdom pathogen F. oxysporum. © 2016 BSPP AND JOHN WILEY & SONS LTD.

  11. Indicine N-oxide binds to tubulin at a distinct site and inhibits the assembly of microtubules: a mechanism for its cytotoxic activity.

    Science.gov (United States)

    Appadurai, Prakash; Rathinasamy, Krishnan

    2014-02-10

    Indicine N-oxide, a pyrrolizidine alkaloid present in the plant Heliotropium indicum had shown promising cytotoxic activity in various tumor models. The compound exhibited severe toxicity to hepatocytes and bone marrow cells. The present work was aimed to evaluate the molecular mechanism of the toxicity of indicine N-oxide. We found that indicine N-oxide inhibited the proliferation of various cancer cell lines in a concentration dependent manner with IC50 ranging from 46 to 100 μM. At the half maximal inhibitory concentration it blocked the cell cycle progression at mitosis without significantly altering the organization of the spindle and interphase microtubules. The toxicities of the compound at higher concentrations are attributed to its severe depolymerizing effect on both the interphase and spindle microtubules. Binding studies using purified goat brain tubulin indicated that indicine N-oxide binds to tubulin at a distinct site not shared by colchicine or taxol. It decreased the polymer mass of both purified tubulin and MAP-rich tubulin. It was found to induce cleavage of DNA using pUC18 plasmid. The interactions of indicine N-oxide on DNA were also confirmed by computational analysis; which predicted its binding site at the minor groove of DNA. These studies bring to light that the toxicities of indicine N-oxide were due to its DNA damaging effects and depolymerization of microtubules. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. Microglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a rAAV based model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Vanesa Sanchez-Guajardo

    Full Text Available Post-mortem analysis of brains from Parkinson's disease (PD patients strongly supports microglia activation and adaptive immunity as factors contributing to disease progression. Such responses may be triggered by alpha-synuclein (alpha-syn, which is known to be the main constituent of the aggregated proteins found in Lewy bodies in the brains of PD patients. To investigate this we used a recombinant viral vector to express human alpha-syn in rat midbrain at levels that induced neuronal pathology either in the absence or the presence of dopaminergic cell death, thereby mimicking early or late stages of the disease. Microglia activation was assessed by stereological quantification of Mac1+ cells, as well as the expression patterns of CD68 and MCH II. In our study, when alpha-syn induced neuronal pathology but not cell death, a fast transient increase in microglia cell numbers resulted in the long-term induction of MHC II+ microglia, denoting antigen-presenting ability. On the other hand, when alpha-syn induced both neuronal pathology and cell death, there was a delayed increase in microglia cell numbers, which correlated with long-lasting CD68 expression and a morphology reminiscent of peripheral macrophages. In addition T-lymphocyte infiltration, as judged by the presence of CD4+ and CD8+ cells, showed distinct kinetics depending on the degree of neurodegeneration, and was significantly higher when cell death occurred. We have thus for the first time shown that the microglial response differs depending on whether alpha-syn expression results on cell death or not, suggesting that microglia may play different roles during disease progression. Furthermore, our data suggest that the microglial response is modulated by early events related to alpha-syn expression in substantia nigra and persists at the long term.

  13. Distinct alterations in motor & reward seeking behavior are dependent on the gestational age of exposure to LPS-induced maternal immune activation.

    Science.gov (United States)

    Straley, Megan E; Van Oeffelen, Wesley; Theze, Sarah; Sullivan, Aideen M; O'Mahony, Siobhain M; Cryan, John F; O'Keeffe, Gerard W

    2017-07-01

    The dopaminergic system is involved in motivation, reward and the associated motor activities. Mesodiencephalic dopaminergic neurons in the ventral tegmental area (VTA) regulate motivation and reward, whereas those in the substantia nigra (SN) are essential for motor control. Defective VTA dopaminergic transmission has been implicated in schizophrenia, drug addiction and depression whereas dopaminergic neurons in the SN are lost in Parkinson's disease. Maternal immune activation (MIA) leading to in utero inflammation has been proposed to be a risk factor for these disorders, yet it is unclear how this stimulus can lead to the diverse disturbances in dopaminergic-driven behaviors that emerge at different stages of life in affected offspring. Here we report that gestational age is a critical determinant of the subsequent alterations in dopaminergic-driven behavior in rat offspring exposed to lipopolysaccharide (LPS)-induced MIA. Behavioral analysis revealed that MIA on gestational day 16 but not gestational day 12 resulted in biphasic impairments in motor behavior. Specifically, motor impairments were evident in early life, which were resolved by adolescence, but subsequently re-emerged in adulthood. In contrast, reward seeking behaviors were altered in offspring exposed MIA on gestational day 12. These changes were not due to a loss of dopaminergic neurons per se in the postnatal period, suggesting that they reflect functional changes in dopaminergic systems. This highlights that gestational age may be a key determinant of how MIA leads to distinct alterations in dopaminergic-driven behavior across the lifespan of affected offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. IMPLEMESTASI E-KRS PADA PROGRAM STUDI D4 TEKNIK INFORMATIKA

    Directory of Open Access Journals (Sweden)

    Chairul Fikri Ramadhan

    2016-08-01

    Full Text Available Seiring dengan kemajuan ilmu pengetahuan dan teknologi, komputer telah digunakan untuk berbagai keperluan dan menjadi bagian yang sangat penting untuk menunjang aktifitas maupun pekerjaan dalam segala hal. Pemanfaatan atau pengembangan sistem komputer ini sangat membantu pekerjaan seseorang termasuk dalam kegiatan akademik. Termasuk pula perguruan tinggi Politeknik Harapan Bersama Tegal, khususnya Program Studi D4 Teknik Informatika. Pada setiap perguruan tinggi tentunya memiliki system pengisian KRS sebagai syarat untuk mengambil matakuliah yang akan ditempuh disemester depan. Namun banyak perguruan tinggi yang masih menggunakan sistem pengisian KRS dengan cara manual termasuk pada Program Studi D4 Teknik Informatika Politeknik Harapan Bersama Tegal.Berdasarkan kondisi tersebut, maka diperlukan perencanaan sebagai langkah awal, menganalisis data yang diperlukan, merancang sistem yang ada menggunakan UML, serta penerapannya untuk mengimplementasikan  sebuah sistem E-KRS pada program studi D4 Teknik Informatika dengan tujuan untuk menghasilkan sebuah aplikasi E-KRS pada Program Studi D4 Teknik Informatika sehingga mempermudah mahasiswa dalam mengisi formulir KRS secara online. Sistem dirancang dan dibangun dengan menggunakan teknologi PHP serta Framework Code Igniter, Xampp sebagai web server, MySql sebagai database server. Dan Adobe Dreamweaver sebagai editor. Kata kunci: Tegal, E-KRS, Program Studi D4 Teknik Informatika

  15. Crystal structure and stability of LiAlD4 with TiF3 additive

    International Nuclear Information System (INIS)

    Brinks, H.W.; Fossdal, A.; Fonnelop, J.E.; Hauback, B.C.

    2005-01-01

    LiAlD 4 samples with TiF 3 additives have been investigated by synchrotron X-ray diffraction, neutron diffraction and a Sieverts-type apparatus. Directly after ball milling there are no signs of any Ti-containing phases, and the unit-cell of LiAlD 4 and Al give no indication of any solid solutions. Hence it is concluded that the Ti is in an amorphous state directly after ball milling. Furthermore, no LiF was observed in the samples. Based on Sieverts-type measurements the plateau pressure at 80 deg C has been proved to be higher than 85 bar. Samples stored in a glove box are slowly desorbed, and after 6 months for a LiAlD 4 + TiF 3 sample, the reaction to LiD + Al is nearly finished

  16. MSSM-like from SU5×D4 models

    Directory of Open Access Journals (Sweden)

    R. Ahl Laamara

    2016-05-01

    Full Text Available Using finite discrete group characters and symmetry breaking by hyperflux as well as constraints on top-quark family, we study minimal low energy effective theory following from SU5×D4 models embedded in F-theory with non-abelian flux. Matter curves spectrum of the models is obtained from SU5×S5 theory with monodromy S5 by performing two breakings: first from symmetric group S5 to S4 subsymmetry, and next to dihedral D4 subgroup. As a consequence, and depending on the ways of decomposing triplets of S4, we end with three types of D4-models. Explicit constructions of these theories are given and a MSSM-like spectrum is derived.

  17. An evolutionary conserved region (ECR in the human dopamine receptor D4 gene supports reporter gene expression in primary cultures derived from the rat cortex

    Directory of Open Access Journals (Sweden)

    Haddley Kate

    2011-05-01

    Full Text Available Abstract Background Detecting functional variants contributing to diversity of behaviour is crucial for dissecting genetics of complex behaviours. At a molecular level, characterisation of variation in exons has been studied as they are easily identified in the current genome annotation although the functional consequences are less well understood; however, it has been difficult to prioritise regions of non-coding DNA in which genetic variation could also have significant functional consequences. Comparison of multiple vertebrate genomes has allowed the identification of non-coding evolutionary conserved regions (ECRs, in which the degree of conservation can be comparable with exonic regions suggesting functional significance. Results We identified ECRs at the dopamine receptor D4 gene locus, an important gene for human behaviours. The most conserved non-coding ECR (D4ECR1 supported high reporter gene expression in primary cultures derived from neonate rat frontal cortex. Computer aided analysis of the sequence of the D4ECR1 indicated the potential transcription factors that could modulate its function. D4ECR1 contained multiple consensus sequences for binding the transcription factor Sp1, a factor previously implicated in DRD4 expression. Co-transfection experiments demonstrated that overexpression of Sp1 significantly decreased the activity of the D4ECR1 in vitro. Conclusion Bioinformatic analysis complemented by functional analysis of the DRD4 gene locus has identified a a strong enhancer that functions in neurons and b a transcription factor that may modulate the function of that enhancer.

  18. Association between dopamine D4 receptor polymorphism and age related changes in brain glucose metabolism.

    Directory of Open Access Journals (Sweden)

    Nora D Volkow

    Full Text Available Aging is associated with reductions in brain glucose metabolism in some cortical and subcortical regions, but the rate of decrease varies significantly between individuals, likely reflecting genetic and environmental factors and their interactions. Here we test the hypothesis that the variant of the dopamine receptor D4 (DRD4 gene (VNTR in exon 3, which has been associated with novelty seeking and sensitivity to environmental stimuli (negative and positive including the beneficial effects of physical activity on longevity, influence the effects of aging on the human brain. We used positron emission tomography (PET and [(18F]fluoro-D-glucose ((18FDG to measure brain glucose metabolism (marker of brain function under baseline conditions (no stimulation in 82 healthy individuals (age range 22-55 years. We determined their DRD4 genotype and found an interaction with age: individuals who did not carry the 7-repeat allele (7R-, n = 53 had a significant (p<0.0001 negative association between age and relative glucose metabolism (normalized to whole brain glucose metabolism in frontal (r = -0.52, temporal (r = -0.51 and striatal regions (r = -0.47, p<0.001; such that older individuals had lower metabolism than younger ones. In contrast, for carriers of the 7R allele (7R+ n = 29, these correlations with age were not significant and they only showed a positive association with cerebellar glucose metabolism (r = +0.55; p = 0.002. Regression slopes of regional brain glucose metabolism with age differed significantly between the 7R+ and 7R- groups in cerebellum, inferior temporal cortex and striatum. These results provide evidence that the DRD4 genotype might modulate the associations between regional brain glucose metabolism and age and that the carriers of the 7R allele appear to be less sensitive to the effects of age on brain glucose metabolism.

  19. Methodology and application of the WIMS-D4M fission product data

    International Nuclear Information System (INIS)

    Mo, S.C.

    1995-01-01

    The WIMS-D4 code has been modified (WIMS-D4m) to generate burn-up dependent microscopic cross sections for use in full core depletion calculations. The calculation of neutron absorption by fission products can be obtained from a reduced fission-product-chain model that includes the 135 Xe and 149 Sm chains, and a lumped fission product to account for the absorption by fission products not explicitly treated. Burn-up calculations were performed for the ANS MEU core using WIMS and EPRI-CELL cross sections. The calculated eigenvalues and material loadings are in good agreements

  20. Is there a minimum length in D=4 lattice quantum gravity?

    International Nuclear Information System (INIS)

    Greensite, J.

    1990-11-01

    It is argued that, as in string theory, a minimum length exists in D=4 quantum gravity. The argument is based on a (naive) lattice regularization of tetrad gravity, where it appears that any formal reduction of the lattice spacing ε=χ n+1 -x n is countered by an increase in metric fluctuations. In D=4 dimensions, these fluctuations prevent the average physical separation between neighboring lattice points from falling below a certain minimum, which is on the order of the Planck length. (orig.)

  1. Small and intermediate conductance Ca(2+)-activated K+ channels confer distinctive patterns of distribution in human tissues and differential cellular localisation in the colon and corpus cavernosum.

    Science.gov (United States)

    Chen, Mao Xiang; Gorman, Shelby A; Benson, Bill; Singh, Kuljit; Hieble, J Paul; Michel, Martin C; Tate, Simon N; Trezise, Derek J

    2004-06-01

    The SK/IK family of small and intermediate conductance calcium-activated potassium channels contains four members, SK1, SK2, SK3 and IK1, and is important for the regulation of a variety of neuronal and non-neuronal functions. In this study we have analysed the distribution of these channels in human tissues and their cellular localisation in samples of colon and corpus cavernosum. SK1 mRNA was detected almost exclusively in neuronal tissues. SK2 mRNA distribution was restricted but more widespread than SK1, and was detected in adrenal gland, brain, prostate, bladder, liver and heart. SK3 mRNA was detected in almost every tissue examined. It was highly expressed in brain and in smooth muscle-rich tissues including the clitoris and the corpus cavernosum, and expression in the corpus cavernosum was upregulated up to 5-fold in patients undergoing sex-change operations. IK1 mRNA was present in surface-rich, secretory and inflammatory cell-rich tissues, highest in the trachea, prostate, placenta and salivary glands. In detailed immunohistochemical studies of the colon and the corpus cavernosum, SK1-like immunoreactivity was observed in the enteric neurons. SK3-like immunoreactivity was observed strongly in smooth muscle and vascular endothelium. IK1-like immunoreactivity was mainly observed in inflammatory cells and enteric neurons of the colon, but absent in corpus cavernosum. These distinctive patterns of distribution suggest that these channels are likely to have different biological functions and could be specifically targeted for a number of human diseases, such as irritable bowel syndrome, hypertension and erectile dysfunction.

  2. Evolution of Enzymatic Activities in the Enolase Superfamily: Stereochemically Distinct Mechanisms in Two Families of cis,cis-Muconate Lactonizing Enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, A.; Fedorov, A; Fedorov, E; Schnoes, A; Glasner, M; Burley, S; Babbitt, P; Almo, S; Gerlt, J

    2009-01-01

    The mechanistically diverse enolase superfamily is a paradigm for elucidating Nature's strategies for divergent evolution of enzyme function. Each of the different reactions catalyzed by members of the superfamily is initiated by abstraction of the a-proton of a carboxylate substrate that is coordinated to an essential Mg2+. The muconate lactonizing enzyme (MLE) from Pseudomonas putida, a member of a family that catalyzes the syn-cycloisomerization of cis,cis-muconate to (4S)-muconolactone in the e-ketoadipate pathway, has provided critical insights into the structural bases for evolution of function within the superfamily. A second, divergent family of homologous MLEs that catalyzes anti-cycloisomerization has been identified. Structures of members of both families liganded with the common (4S)-muconolactone product (syn, Pseudomonas fluorescens, gi 70731221; anti, Mycobacterium smegmatis, gi 118470554) document that the conserved Lys at the end of the second e-strand in the (e/a)7e-barrel domain serves as the acid catalyst in both reactions. The different stereochemical courses (syn and anti) result from different structural strategies for determining substrate specificity: although the distal carboxylate group of the cis,cis-muconate substrate attacks the same face of the proximal double bond, opposite faces of the resulting enolate anion intermediate are presented to the conserved Lys acid catalyst. The discovery of two families of homologous, but stereochemically distinct, MLEs likely provides an example of 'pseudoconvergent' evolution of the same function from different homologous progenitors within the enolase superfamily, in which different spatial arrangements of active site functional groups and substrate specificity determinants support catalysis of the same reaction.

  3. Evolution of Enzymatic Activities in the Enolase Superfamily: Stereochemically Distinct Mechanisms in Two Families of cis,cis-Muconate Lactonizing Enzymes†

    Science.gov (United States)

    Sakai, Ayano; Fedorov, Alexander A.; Fedorov, Elena V.; Schnoes, Alexandra M.; Glasner, Margaret E.; Brown, Shoshana; Rutter, Marc E.; Bain, Kevin; Chang, Shawn; Gheyi, Tarun; Sauder, J. Michael; Burley, Stephen K.; Babbitt, Patricia C.; Almo, Steven C.; Gerlt, John A.

    2009-01-01

    The mechanistically diverse enolase superfamily is a paradigm for elucidating Nature’s strategies for divergent evolution of enzyme function. Each of the different reactions catalyzed by members of the superfamily is initiated by abstraction of the α-proton of a carboxylate substrate that is coordinated to an essential Mg2+. The muconate lactonizing enzyme (MLE) from Pseudomonas putida, a member of a family that catalyzes the syn-cycloisomerization of cis,cis-muconate to (4S)-muconolactone in the β-ketoadipate pathway, has provided critical insights into the structural bases for evolution of function within the superfamily. A second, divergent family of homologues MLEs that catalyzes anti-cycloisomerization has been identified. Structures of members of both families liganded with the common (4S)-muconolactone product (syn, Pseudomonas fluorescens, GI:70731221; anti, Mycobacterium smegmatis, GI:118470554) document that the conserved Lys at the end of the second β-strand in the (β/α)7β-barrel domain serves as the acid catalyst in both reactions. The different stereochemical courses (syn and anti) result from different structural strategies for determining substrate specificity: although the distal carboxylate group of the cis,cis-muconate substrate attacks the same face of the proximal double bond, opposite faces of the resulting enolate anion intermediate are presented to the conserved Lys acid catalyst. The discovery of two families of homologous, but stereochemically distinct, MLEs likely provides an example of “pseudoconvergent” evolution of the same function from different homologous progenitors within the enolase superfamily, in which different spatial arrangements of active site functional groups and substrate specificity determinants support catalysis of the same reaction. PMID:19220063

  4. A context dependent interpretation of inconsistencies in 2D : 4D findings: The moderating role of status relevance

    NARCIS (Netherlands)

    Millet, Kobe; Buehler, Florian

    2018-01-01

    Whereas direct relationships between 2D:4D and dominance related attitudes or behavior often turn out to be weak, some literature suggests that the relation between 2D:4D and dominance is context-specific. That is, especially in status-challenging situations 2D:4D may be related to dominant behavior

  5. Peroxisomes in Different Skeletal Cell Types during Intramembranous and Endochondral Ossification and Their Regulation during Osteoblast Differentiation by Distinct Peroxisome Proliferator-Activated Receptors.

    Directory of Open Access Journals (Sweden)

    Guofeng Qian

    Full Text Available Ossification defects leading to craniofacial dysmorphism or rhizomelia are typical phenotypes in patients and corresponding knockout mouse models with distinct peroxisomal disorders. Despite these obvious skeletal pathologies, to date no careful analysis exists on the distribution and function of peroxisomes in skeletal tissues and their alterations during ossification. Therefore, we analyzed the peroxisomal compartment in different cell types of mouse cartilage and bone as well as in primary cultures of calvarial osteoblasts. The peroxisome number and metabolism strongly increased in chondrocytes during endochondral ossification from the reserve to the hypertrophic zone, whereas in bone, metabolically active osteoblasts contained a higher numerical abundance of this organelle than osteocytes. The high abundance of peroxisomes in these skeletal cell types is reflected by high levels of Pex11β gene expression. During culture, calvarial pre-osteoblasts differentiated into secretory osteoblasts accompanied by peroxisome proliferation and increased levels of peroxisomal genes and proteins. Since many peroxisomal genes contain a PPAR-responsive element, we analyzed the gene expression of PPARɑ/ß/ɣ in calvarial osteoblasts and MC3T3-E1 cells, revealing higher levels for PPARß than for PPARɑ and PPARɣ. Treatment with different PPAR agonists and antagonists not only changed the peroxisomal compartment and associated gene expression, but also induced complex alterations of the gene expression patterns of the other PPAR family members. Studies in M3CT3-E1 cells showed that the PPARß agonist GW0742 activated the PPRE-mediated luciferase expression and up-regulated peroxisomal gene transcription (Pex11, Pex13, Pex14, Acox1 and Cat, whereas the PPARß antagonist GSK0660 led to repression of the PPRE and a decrease of the corresponding mRNA levels. In the same way, treatment of calvarial osteoblasts with GW0742 increased in peroxisome number and

  6. 300 Area D4 Project 2nd Quarter FY06 Building Completion Report

    International Nuclear Information System (INIS)

    Smith, David S.

    2006-01-01

    This report documents the deactivation, decontamination, decommissioning, and demolition of 16 buildings in the 300 Area of the Hanford Site. The D4 of these facilities included characterization, engineering, removal of hazardous and radiologically contaminated materials, equipment removal, utility disconnection, deactivation, decontamination, demolition of the structure, and stabilization or removal of the remaining slab and foundation as appropriate.

  7. 300 Area D4 Project 3rd Quarter Fiscal Year 2006 Building Completion Report

    International Nuclear Information System (INIS)

    Smith, D.S.

    2006-01-01

    This report documents the deactivation, decontamination, decommissioning, and demolition of five buildings in the 300 Area of the Hanford Site. The D4 of these facilities included characterization, engineering, removal of hazardous and radiologically contaminated materials, equipment removal, utility disconnection, deactivation, decontamination, demolition of the structure, and stabilization or removal of the remaining slab and foundation as appropriate.

  8. The D4-D8 Brane System and Five Dimensional Fixed Points

    OpenAIRE

    Brandhuber, A; Oz, Y

    1999-01-01

    We construct dual Type I' string descriptions to five dimensional supersymmetric fixed points with $E_{N_f+1}$ global symmetry. The background is obtained as the near horizon geometry of the D4-D8 brane system in massive Type IIA supergravity. We use the dual description to deduce some properties of the fixed points.

  9. Effective potential in N=1, d=4 supergravity coupled to the Volkov-Akulov field

    International Nuclear Information System (INIS)

    Jasinschi, R.S.; Smith, A.W.

    1984-01-01

    The only-loop effective potential for N=1, d=4 supergravity theory coupled to the Volkov-Akulov field is calculated. Then it is shown that after an ajustment of some parameters the local supersymmetry is dynamically broken and as a consequence the gravitino acquires mass. (Author) [pt

  10. Data for Environmental Modeling (D4EM): Background and Applications of Data Automation

    Science.gov (United States)

    The Data for Environmental Modeling (D4EM) project demonstrates the development of a comprehensive set of open source software tools that overcome obstacles to accessing data needed by automating the process of populating model input data sets with environmental data available fr...

  11. 2D: 4D Is Negatively Associated to Aggressive Dominance in Men: A Response to Voracek

    NARCIS (Netherlands)

    van der Meij, L.; Almela, M.; Salvador, A.; Buunk, A.P.

    2013-01-01

    We do not agree with the interpretation and evaluation of our article by Voracek. We feel that our results and our interpretation of the results are supported by our data analyses and do add to the current understanding of the relationship between 2D:4D and personality. We feel confident we can

  12. Data of evolutionary structure change: 1BXSC-2D4ED [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available KIQ-GRTIP >GGG - > ATOM 8584 CA ...bID> D 2D4ED AEHAMEDRTFP ...>GGG > ATOM 13219 CA ALA D 139 -2.022 -17.489 1.680 1.0...AFQ---RWSRT >HHHHH---HGGG > ATOM...XS C 1BXSC RQAFQIGSPWRTM

  13. N=2, D=4 supersymmetric σ-models and Hamiltonian mechanics

    International Nuclear Information System (INIS)

    Galperin, A.; Ogievetsky, V.

    1991-05-01

    A deep similarity is established between the Hamiltonian mechanics of point particle and supersymmetric N=2, D=4 σ-models formulated within harmonic superspace. An essential part of the latter, the sphere S 2 , comes out as a counterpart of the time variable. (author). 7 refs

  14. Digit Ratio (2D:4D and Gender Inequalities Across Nations

    Directory of Open Access Journals (Sweden)

    John T. Manning

    2014-10-01

    Full Text Available Gender inequality varies across nations, where such inequality is defined as the disproportionate representation of one sex over the other in desirable social, economic, and biological roles (typically male over female. Thus in Norway, 40% of parliamentarians are women, in the USA 17%, and in Saudi Arabia 0%. Some of this variation is associated with economic prosperity but there is evidence that this cause and effect can go in either direction. Here we show that within a population the average ratio of index (2D to ring (4D finger lengths (2D:4D—a proxy measure of the relative degree to which offspring is exposed in utero to testosterone versus estrogen—is correlated with measures of gender inequality between nations. We compared male and female 2D:4D ratios to female parliamentary representation, labor force participation, female education level, maternal mortality rates, and juvenile pregnancy rates per nation in a sample of 29 countries. We found those nations who showed higher than expected female fetal exposure to testosterone (low 2D:4D and lower than expected male exposure to fetal testosterone (high 2D:4D had higher rates of female parliamentary representation, and higher female labor force participation. In short, the more similar the two sexes were in 2D:4D, the more equal were the two sexes in parliamentary and labor force participation. The other variables were not as strongly correlated. We suggest that higher than expected fetal testosterone in females and lower fetal testosterone in males may lead to high female representation in the national labor force and in parliament.

  15. The inflammatory mediator leukotriene D4 induces subcellular β-catenin translocation and migration of colon cancer cells

    International Nuclear Information System (INIS)

    Salim, Tavga; Sand-Dejmek, Janna; Sjölander, Anita

    2014-01-01

    The abnormal activation of the Wnt/β-catenin pathway frequently occurs in colorectal cancer. The nuclear translocation of β-catenin activates the transcription of target genes that promote cell proliferation, survival, and invasion. The pro-inflammatory mediator leukotriene D 4 (LTD 4 ) exerts its effects through the CysLT 1 receptor. We previously reported an upregulation of CysLT 1 R in patients with colon cancer, suggesting the importance of leukotrienes in colon cancer. The aim of this study was to investigate the impact of LTD 4 on Wnt/β-catenin signaling and its effects on proliferation and migration of colon cancer cells. LTD 4 stimulation led to an increase in β-catenin expression, β-catenin nuclear translocation and the subsequent transcription of MYC and CCND1. Furthermore, LTD 4 significantly reduced the expression of E-cadherin and β-catenin at the plasma membrane and increased the migration and proliferation of HCT116 colon cancer cells. The effects of LTD 4 can be blocked by the inhibition of CysLT 1 R. Furthermore, LTD 4 induced the inhibition of glycogen synthase kinase 3 (GSK)-3β activity, indicating a crosstalk between the G-protein-coupled receptor CysLT 1 and the Wnt/β-catenin pathway. In conclusion, LTD 4 , which can be secreted from macrophages and leukocytes in the tumor microenvironment, induces β-catenin translocation and the activation of β-catenin target genes, resulting in the increased proliferation and migration of colon cancer cells. - Highlights: • Leukotriene D 4 (LTD 4 ) lowers membrane β-catenin but increases nuclear β-catenin levels in colon cancer cells. • In agreement, LTD 4 triggers inactivation of GSK-3β, activation of TCF/LEF and increased expression of Cyclin D1 and c-Myc. • LTD 4 also caused a significant reduction in the expression of E-cadherin and an increased migration of colon cancer cells

  16. [18F]fluoromethylated phenyl-pyrroles and 7-azaindole analog as potential dopamine D4 receptor imaging agents

    International Nuclear Information System (INIS)

    Ji, D. Y.; Oh, S. Z.; Choi, Y. S.; Lee, K. C.; Kim, S. E.; Choi, Y.; Lee, K. H.; Kim, B. T.

    1997-01-01

    An association between the dopamine D 4 receptor and schizophrenia was recently suggested and the D 4 receptor antagonists may thus have potential in elucidating the role of the receptor in schizophrenic patients. The purpose of this study was to develop some of these antagonists as potential dopamine D 4 receptor imaging agents for PET. We have prepared 1-(3-[ 18 F]fluoromethylphenyl)-3-([4-(pyridin-2-yl)piperazin-1-yl)methyl) pyrrole (1), 1-(3-[ 18 F]fluoromethylphenyl)-3-([4-(pyridin-2-yl)piperazin-1-yl)methyl) pyrrole (2), and 3-([4-(4-[ 18 F]fluoro methylbenzyl)piperazin-1-yl)methyl)-1H-pyrrolo(2,3,-b)pyridine (3) as potential imaging agents for the dopamine D 4 receptor for PET. The compounds [ 18 F]1 and [ 18 F]2 were prepared by coupling of (3-[ 18 F]fluoromethylphenyl)-pyrrol-1- yl-3-aldehyde and the piperazine moiety in the presence of NaBH 3 CN. The [ 18 F]fluorinated aldehyde was obtained in 60-85% yield by the displacement of the corresponding mesylate with F-18-(THF, 90 .deg. C, 5 min). HPLC purification (Alltech Econosil C-18 columm, 250 x 10 mm, 35: 65 = 0.1M NH 4 CI 2 H : CH 3 OH, 4 ml/min, t R =26.6 min) gave the [ 18 F]1 and [ 18 F]2 in 7-12% yield. In the case of azaindole 3, a methlene link was inserted between the piperazinyl and a fluoromethyl phenyl group. Radiochemical synthesis of the [ 18 F]3 was carried out by coupling of the piperazne moiety and [ 18 F]fluoromethylbenzyl mesylate in the presence of NEt 3 (3:1-CH 3 CN: DMF, 120 .deg. C, 30 min). Purification was carried out by HPLC using a C-18 column (Alltech Econosil, 50 x 10 mm, 100% 0.1M NH 4 CO 2 H for 5 min followed by 40:60=0.1 M NH 4 CO 2 H : MeOH, 4 ml/min t R =28.7 min). The time of synthesis including HPLC purification was 100 min. The overall yield of [ 18 F]3 was 10-15% with a radiochemical purity better than 97% and a specific activity greater than 1000 ci/mmol

  17. Fear Memory Recall Potentiates Opiate Reward Sensitivity through Dissociable Dopamine D1 vs. D4 Receptor-Dependent Memory Mechanisms in the Prefrontal Cortex.

    Science.gov (United States)

    Li, Jing Jing; Szkudlarek, Hanna; Renard, Justine; Hudson, Roger; Rushlow, Walter; Laviolette, Steven R

    2018-04-23

    Disturbances in prefrontal cortical (PFC) dopamine (DA) transmission are well-established features of psychiatric disorders involving pathological memory processing, such as post-traumatic stress disorder (PTSD) and opioid addiction. Transmission through PFC DA D4 receptors (D4R) has been shown to potentiate the emotional salience of normally non-salient emotional memories whereas transmission through PFC DA D1 receptors (D1R) has been demonstrated to selectively block recall of reward or aversion-related associative memories. In the present study, using a combination of fear conditioning and opiate reward conditioning in male rats, we examined the role of PFC D4/D1R signaling during the processing of fear-related memory acquisition and recall and subsequent sensitivity to opiate reward memory formation. We report that PFC D4R activation potentiates the salience of normally sub-threshold fear conditioning memory cues and simultaneously potentiates the rewarding effects of systemic or intra-ventral tegmental area (VTA) morphine conditioning cues. In contrast, blocking the recall of salient fear memories with intra-PFC D1R activation, blocks the ability of fear memory recall to potentiate systemic or intra-VTA morphine place preference. These effects were dependent upon dissociable PFC phosphorylation states involving calcium-calmodulin-kinase II (CaMKII-α) or extracellular-signal-related-kinase 1-2 (ERK 1/2), following intra-PFC D4 or D1R activation, respectively. Together, these findings reveal new insights into how aberrant PFC DAergic transmission and associated downstream molecular signaling pathways may modulate fear-related emotional memory processing and concomitantly increase opioid addiction vulnerability. Significance Statement: Post-traumatic stress disorder is highly comorbid with addiction. In this study, we use a translational model of fear memory conditioning to examine how transmission through dopamine D1 or D4 receptors, in the prefrontal cortex

  18. Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes

    DEFF Research Database (Denmark)

    Petrovic, Natasa; Walden, Tomas B; Shabalina, Irina G

    2009-01-01

    The recent insight that brown adipocytes and muscle cells share a common origin and in this respect are distinct from white adipocytes has spurred questions concerning the origin and molecular characteristics of the UCP1-expressing cells observed in classic white adipose tissue depots under certain...... physiological or pharmacological conditions. Examining precursors from the purest white adipose tissue depot (epididymal), we report here that chronic treatment with the peroxisome proliferator-activated receptor gamma agonist rosiglitazone promotes not only the expression of PGC-1alpha and mitochondriogenesis...... associated with classic brown adipocytes (Zic1, Lhx8, Meox2, and characteristically PRDM16) or for myocyte-associated genes (myogenin and myomirs (muscle-specific microRNAs)) and retain white fat characteristics such as Hoxc9 expression. Co-culture experiments verify that the UCP1-expressing cells...

  19. Spread of Measles Virus D4-Hamburg, Europe, 2008–2011

    Science.gov (United States)

    Mihneva, Zefira; Gold, Hermann; Baumgarte, Sigrid; Baillot, Armin; Helble, Rudolph; Roggendorf, Hedwig; Bosevska, Golubinka; Nedeljkovic, Jasminka; Makowka, Agata; Hutse, Veronik; Holzmann, Heidemarie; Aberle, Stefan W.; Cordey, Samuel; Necula, Gheorghe; Mentis, Andreas; Korukluoğlu, Gulay; Carr, Michael; Brown, Kevin E.; Hübschen, Judith M.; Muller, Claude P.; Mulders, Mick N.; Santibanez, Sabine

    2011-01-01

    A new strain of measles virus, D4-Hamburg, was imported from London to Hamburg in December 2008 and subsequently spread to Bulgaria, where an outbreak of >24,300 cases was observed. We analyzed spread of the virus to demonstrate the importance of addressing hard-to-reach communities within the World Health Organization European Region regarding access to medical care and vaccination campaigns. The D4-Hamburg strain appeared during 2009–2011 in Poland, Ireland, Northern Ireland, Austria, Greece, Romania, Turkey, Macedonia, Serbia, Switzerland, and Belgium and was repeatedly reimported to Germany. The strain was present in Europe for >27 months and led to >25,000 cases in 12 countries. Spread of the virus was prevalently but not exclusively associated with travel by persons in the Roma ethnic group; because this travel extends beyond the borders of any European country, measures to prevent the spread of measles should be implemented by the region as a whole. PMID:21801615

  20. An off-shell superspace reformulation of D = 4, N = 4 super-Yang-Mills theory

    Energy Technology Data Exchange (ETDEWEB)

    Cederwall, Martin [Division for Theoretical Physics, Department of Physics, Chalmers University of Technology, Gothenburg (Sweden)

    2018-01-15

    D = 4, N = 4 super-Yang-Mills theory has an off-shell superspace formulation in terms of pure spinor superfields, which is directly inherited from the D = 10 theory. That superspace, in particular the choice of pure spinor variables, is less suitable for dealing with fields that are inherently 4-dimensional, such as the superfields based on the scalars, which are gauge-covariant, and traces of powers of scalars, which are gauge-invariant. We give a reformulation of D = 4, N = 4 super-Yang-Mills theory in N = 4 superspace, using inherently 4-dimensional pure spinors. All local degrees of freedom reside in a superfield based on the physical scalars. The formalism should be suited for calculations of correlators of traces of scalar superfields. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  1. Fluid/gravity correspondence: second order transport coefficients in compactified D4-branes

    International Nuclear Information System (INIS)

    Wu, Chao; Chen, Yidian; Huang, Mei

    2017-01-01

    We develop the boundary derivative expansion (BDE) formalism of fluid/gravity correspondence to nonconformal version through the compactified, near-extremal black D4-brane. We offer an explicit calculation of 9 second order transport coefficients, i.e., the τ π , τ π ∗ , τ Π , λ 1,2,3 and ξ 1,2,3 for the strongly coupled, uncharged and nonconformal relativistic fluid which is the holographic dual of compactified, near extremal black D4-brane. We also show that the nonconformal fluid considered in this work is free of causal problem and admits the Haack-Yarom relation 4λ 1 −λ 2 =2ητ π .

  2. Discounting and Digit Ratio: Low 2D:4D Predicts Patience for a Sample of Females

    Directory of Open Access Journals (Sweden)

    Diego Aycinena

    2018-01-01

    Full Text Available Inter-temporal trade-offs are ubiquitous in human decision making. We study the relationship between preferences over such trade-offs and the ratio of the second digit to that of the forth (2D:4D, a marker for pre-natal exposure to sex hormones. Specifically, we study whether 2D:4D affects discounting. Our sample consists of 419 female participants of a Guatemalan conditional cash transfer program who take part in an experiment. Their choices in the convex time budget (CTB experimental task allow us to make inferences regarding their patience (discounting, while controlling for present-biasedness and preference for smoothing consumption (utility curvature. We find that women with lower digit ratios tend to be more patient.

  3. Manifestation of 12-quark bag state of 4He nucleus in elastic d4He scattering

    International Nuclear Information System (INIS)

    Mosallem, A.M.; Uzhinskij, V.V.

    2002-01-01

    The 4 He d elastic scattering at the momentum of 19.8 GeV/c is analyzed in the framework of the Glauber theory. The scattering amplitude was evaluated using different sets of values of the nucleon-nucleon amplitude parameters and the 4 He density function as a superposition of the Gaussian functions. It is shown that it is impossible to describe simultaneously the p 4 He and d 4 He elastic scattering cross sections using the same set of the NN-amplitude parameters. Inclusion of the twelve-quark bag admixture to the ground state of the 4 He nucleus in the calculations allows one to reproduce the experimental data quite well. It is shown that the admixture manifests itself in the d 4 He elastic scattering in the whole region of the momentum transfer. At small t the effect can be at the level of ∼ 10%. At large t it can be ∼30%

  4. CHST14/D4ST1 deficiency: New form of Ehlers-Danlos syndrome.

    Science.gov (United States)

    Kosho, Tomoki

    2016-02-01

    Carbohydrate sulfotransferase 14/dermatan 4-O-sulfotransferase-1 (CHST14/D4ST1) deficiency represents a specific form of Ehlers-Danlos syndrome (EDS) caused by recessive loss-of-function mutations in CHST14. The disorder has been independently termed "adducted thumb-clubfoot syndrome", "EDS, Kosho type", and "EDS, musculocontractural type". To date, 31 affected patients from 21 families have been described. Clinically, CHST14/D4ST1 deficiency is characterized by multiple congenital malformations (craniofacial features including large fontanelle, hypertelorism, short and downslanting palpebral fissures, blue sclerae, short nose with hypoplastic columella, low-set and rotated ears, high palate, long philtrum, thin upper lip vermilion, small mouth, and micro-retrognathia; multiple congenital contractures including adduction-flexion contractures and talipes equinovarus as well as other visceral or ophthalmological malformations) and progressive multisystem fragility-related complications (skin hyperextensibility, bruisability, and fragility with atrophic scars; recurrent dislocations; progressive talipes or spinal deformities; pneumothorax or pneumohemothorax; large subcutaneous hematomas; and diverticular perforation). Etiologically, multisystem fragility is presumably caused by impaired assembly of collagen fibrils resulting from loss of dermatan sulfate (DS) in the decorin glycosaminoglycan side chain that promotes electrostatic binding between collagen fibrils. This is the first reported human disorder that specifically affects biosynthesis of DS. Its clinical characteristics indicate that CHST14/D4ST1 and, more fundamentally, DS, play a critical role in fetal development and maintenance of connective tissues in multiple organs. Considering that patients with CHST14/D4ST1 deficiency develop progressive multisystem fragility-related manifestations, establishment of a comprehensive and detailed natural history and health-care guidelines as well as further elucidation

  5. Digit ratio (2D:4D) and social integration: an effect of prenatal sex hormones

    OpenAIRE

    Kovářík, Jaromír; Branas-Garza, Pablo; Davidson, Michael W.; Haim, Dotan A.; Carcelli, Shannon; Fowler, James H.

    2017-01-01

    The position people occupy in their social and professional networks is related to their social status and has strong effects on their access to social resources. While attainment of particular positions is driven by behavioral traits, many biological factors predispose individuals to certain behaviors and motivations. Prior work on exposure to fetal androgens (measured by second-to-fourth digit ratio, 2D:4D) shows that it correlates with behaviors and traits related to social status, which m...

  6. D4SCIENCE-II - Report on inter-projects coordination and collaboration

    OpenAIRE

    Castelli, Donatella; Zoppi, Franco

    2010-01-01

    This deliverable reports on the collaborations with other FP7 projects and R&D programmes established by D4Science-II from the beginning of the project until July 2010. The collaborations described are of different nature, as they range from purely technical exchanges involving mutual exploitation of technologies to the sharing of e- Infrastructure resources and to the joint organization of networking and dissemination events. The deliverable presents these collaborations clustered into: (i) ...

  7. D=2 and D=4 realization of κ-conformal algebra

    International Nuclear Information System (INIS)

    Klimek, M.

    1996-01-01

    The generators of κ-conformal transformations leaving the κ-deformed d'Alembert equation invariant are described. The algebraic structure of the conformal extension of the off-shell spin zero realization of κ-Poincare algebra is discussed for D=4. The D=2 off-shell realization of κ-conformal algebra for an arbitrary spin and its commutation relations were studied. 14 refs

  8. Benefits and costs of clearer distinction between networks and sales activities; Nytte og kostnader ved klarere skille mellom nett- og omsetningsvirksomhet

    Energy Technology Data Exchange (ETDEWEB)

    2008-12-15

    There will be substantial socio-economic cost connected to an introduction to a stronger distinction between the grid company and power provider in the vertically integrated companies or companies in the same group, provided information from a variety of network companies and suppliers. Full separation will result in additional costs to society in the order of 300 to 500 million kroner per year. The rewards for society can be expected to be modest, a maximum of two million per year. It may therefore be useful to consider other measures that can help to increase companies 'net neutrality, such as measures that restrict net companies' direct contact with end customers, clearer distinction between the operator and electricity supplier in the communication that takes place and strengthen NVE regulator's role. (AG)

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

    OpenAIRE

    Yakovleva, Lyudmila; Shuman, Stewart

    2012-01-01

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

  10. Stavudine (d4T) concentrations in women receiving post-partum antiretroviral treatment and their breastfeeding infants

    Science.gov (United States)

    Fogel, Jessica M.; Taha, Taha E.; Sun, Jin; Hoover, Donald R.; Parsons, Teresa L.; Kumwenda, Johnstone J.; Mofenson, Lynne M.; Fowler, Mary Glenn; Hendrix, Craig W.; Kumwenda, Newton I.; Eshleman, Susan H.; Mirochnick, Mark

    2012-01-01

    First-line antiretroviral treatment regimens in resource-limited settings used in breastfeeding mothers often include stavudine (d4T). Limited data describing d4T concentrations in breast milk are available. We analyzed d4T concentrations in 52 mother-infant pairs using ultra-performance liquid chromatography-tandem mass spectrometry (lower limit of quantification: 5 ng/ml in plasma, 20 ng/ml in breast milk). Median (interquartile range) d4T concentrations were 86 (36–191) ng/ml in maternal plasma, 151 (48–259) ng/ml in whole milk, 190 (58–296) ng/ml in skim milk, and <5 (<5-<5) ng/ml in infant plasma. While d4T is concentrated in breast milk relative to maternal plasma, the infant d4T dose received from breast milk is very small and not clinically significant. PMID:22614899

  11. Elucidating the role of D4 receptors in mediating attributions of salience to incentive stimuli on Pavlovian conditioned approach and conditioned reinforcement paradigms.

    Science.gov (United States)

    Cocker, P J; Vonder Haar, C; Winstanley, C A

    2016-10-01

    The power of drug-associated cues to instigate drug 'wanting' and consequently promote drug seeking is a corner stone of contemporary theories of addiction. Gambling disorder has recently been added to the pantheon of addictive disorders due to the phenomenological similarities between the diseases. However, the neurobiological mechanism that may mediate increased sensitivity towards conditioned stimuli in addictive disorders is unclear. We have previously demonstrated using a rodent analogue of a simple slot machine that the dopamine D4 receptor is critically engaged in controlling animals' attribution of salience to stimuli associated with reward in this paradigm, and consequently may represent a target for the treatment of gambling disorder. Here, we investigated the role of acute administration of a D4 receptor agonist on animals' responsivity to conditioned stimuli on both a Pavlovian conditioned approach (autoshaping) and a conditioned reinforcement paradigm. Following training on one of the two tasks, separate cohorts of rats (male and female) were administered a dose of PD168077 shown to be maximally effective at precipitating errors in reward expectancy on the rat slot machine task (10mg/kg). However, augmenting the activity of the D4 receptors in this manner did not alter behaviour on either task. These data therefore provide novel evidence that the D4 receptor does not alter incentive motivation in response to cues on simple behavioural tasks. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. The Relationship of Digit Ratio (2D:4D) with Cerebral Lateralization and Grip Strength in Elite Swimmers

    Science.gov (United States)

    Acar, Hakan; Eler, Nebahat

    2018-01-01

    The index finger and the 4th finger ratio (2D:4D) is the indicator of the prenatal testosterone. The aim of this study is to investigate the relationship between 2D:4D, hand preference and hand grip strength in swimmers. A total of 80 elite swimmers, participated in the study. Height, body weight, body mass index (BMI), hand 2D:4D finger…

  13. Digit Ratio (2D:4D, Aggression, and Testosterone in Men Exposed to an Aggressive Video Stimulus

    Directory of Open Access Journals (Sweden)

    Liam P. Kilduff

    2013-07-01

    Full Text Available The relative lengths of the 2nd and 4th digits (2D:4D is a negative biomarker for prenatal testosterone, and low 2D:4D may be associated with aggression. However, the evidence for a 2D:4D-aggression association is mixed. Here we test the hypothesis that 2D:4D is robustly linked to aggression in “challenge” situations in which testosterone is increased. Participants were exposed to an aggressive video and a control video. Aggression was measured after each video and salivary free testosterone levels before and after each video. Compared to the control video, the aggressive video was associated with raised aggression responses and a marginally significant increase in testosterone. Left 2D:4D was negatively correlated with aggression after the aggressive video and the strength of the correlation was higher in those participants who showed the greatest increases in testosterone. Left 2D:4D was also negatively correlated to the difference between aggression scores in the aggressive and control conditions. The control video did not influence testosterone concentrations and there were no associations between 2D:4D and aggression. We conclude that 2D:4D moderates the impact of an aggressive stimulus on aggression, such that an increase in testosterone resulting from a “challenge” is associated with a negative correlation between 2D:4D and aggression.

  14. The 2D:4D Marker and Different Forms of Internet Use Disorder.

    Science.gov (United States)

    Müller, Marko; Brand, Matthias; Mies, Julia; Lachmann, Bernd; Sariyska, Rayna Yordanova; Montag, Christian

    2017-01-01

    Internet use disorder (IUD) presents a growing problem worldwide. Among others, it manifests in loss of control over Internet usage and social problems due to problematic Internet use. Although IUD currently is not an official diagnosis in DSM-5 or ICD-10, mounting evidence suggests that IUD indeed could be categorized as a behavioral addiction. On a systemic neuroscientific level, IUD is well characterized and dysfunctions in the fronto-striatal-limbic loop have been observed in persons being afflicted with IUD. On a molecular level underlying these neural dysfunctions less is known. Therefore, the present research investigates the influence of prenatal testosterone as measured via the 2D:4D marker of the hand on IUD. Testosterone represents an interesting hormonal marker, because sex differences in IUD have been observed, e.g., males show higher tendencies toward Internet gaming disorder (IGD) or females toward overusage of online social networks (both compared to the contrary sex). In N  = 217 participants associations between the 2D:4D marker of the hand and both unspecified IUD and specific forms of IUD were investigated. It appeared that more female hands (right side; characterized by higher digit ratio of the index to the ring finger, i.e., >1, meaning lower prenatal testosterone) were associated with lower IGD ( rho  = -0.17, p  = 0.01, N  = 211). This effect was driven by the facet of loss of control of Internet Gaming in the whole sample ( rho  = -0.20, p  negative association appeared between the facet of loss of control of generalized IUD and the right digit ratio in males underlining earlier work. In sum, the present work demonstrates that the 2D:4D marker is an interesting marker for Internet addiction and can be easily included as a biomarker to understand the biological underpinnings of Internet (over-)usage.

  15. Dopamine receptor D4 promoter hypermethylation increases the risk of drug addiction.

    Science.gov (United States)

    Ji, Huihui; Xu, Xuting; Liu, Guili; Liu, Huifen; Wang, Qinwen; Shen, Wenwen; Li, Longhui; Xie, Xiaohu; Hu, Haochang; Xu, Lei; Zhou, Wenhua; Duan, Shiwei

    2018-02-01

    Heroin and methylamphetamine (METH) are two addictive drugs that cause serious problems for society. Dopamine receptor D4 (DRD4), a key receptor in the dopaminergic system, may facilitate the development of drug addiction. The aim of the present study was to investigate the association between the promoter methylation level of DRD4 gene and drug addiction. Bisulfite pyrosequencing technology was used to measure the methylation levels of DRD4 promoter in 60 drug addicts and 52 matched controls. Significantly higher levels of DRD4 CpG1 and CpG4 methylation were detected in METH and heroin drug addicts compared with controls (Pdrug addiction.

  16. Infrared behaviour of massless QED in space-time dimensions 2<d<4

    International Nuclear Information System (INIS)

    Mitra, Indrajit; Ratabole, Raghunath; Sharatchandra, H.S.

    2005-01-01

    We show that the logarithmic infrared divergences in electron self-energy and vertex function of massless QED in 2+1 dimensions can be removed at all orders of 1/N by an appropriate choice of a non-local gauge. Thus the infrared behaviour given by the leading order in 1/N is not modified by higher order corrections. Our analysis gives a computational scheme for the Amati-Testa model, resulting in a non-trivial conformal invariant field theory for all space-time dimensions 2< d<4

  17. Infrared behaviour of massless QED in space-time dimensions 2<d<4

    Energy Technology Data Exchange (ETDEWEB)

    Mitra, Indrajit [The Institute of Mathematical Sciences, C.I.T. Campus, Taramani P.O., Chennai 600113 (India) and Theory Group, Saha Institute of Nuclear Physics, 1/AF Bidhan-Nagar, Kolkata 700064 (India)]. E-mail: indra@theory.saha.ernet.in; Ratabole, Raghunath [The Institute of Mathematical Sciences, C.I.T. Campus, Taramani P.O., Chennai 600113 (India)]. E-mail: raghu@imsc.res.in; Sharatchandra, H.S. [The Institute of Mathematical Sciences, C.I.T. Campus, Taramani P.O., Chennai 600113 (India)]. E-mail: sharat@imsc.res.in

    2005-04-07

    We show that the logarithmic infrared divergences in electron self-energy and vertex function of massless QED in 2+1 dimensions can be removed at all orders of 1/N by an appropriate choice of a non-local gauge. Thus the infrared behaviour given by the leading order in 1/N is not modified by higher order corrections. Our analysis gives a computational scheme for the Amati-Testa model, resulting in a non-trivial conformal invariant field theory for all space-time dimensions 2<d<4.

  18. Conformational analysis and vibrational studies of ethylenediamine-d4, using DFT method

    International Nuclear Information System (INIS)

    Catikkas, B.

    2010-01-01

    In this work, conformational analysis and quantum chemical calculations of ethylenediamine-d4 were carried out. The geometry optimization and the geometric parameters (bond length, bond angle and tortion angle) were calculated. The Infrared and Raman frequencies of fundamental modes of the most stable conformer were determined. Calculations were carried out by using the MPW1PW91/6-311+G(d,p) method and Gaussian03 and GaussView3.0 programs. Populations of the conformers was calculated. Vibrational assignments of the title molecule were calculated by using Scaled Quantum Mechanical (SQM) analysis. Calculated values were compared with the experimental ones.

  19. The supersymmetric configurations of N=2, d=4 supergravity coupled to vector supermultiplets

    CERN Document Server

    Meessen, P

    2006-01-01

    We classify all the supersymmetric configurations of ungauged N=2,d=4 supergravity coupled to n vector multiplets and determine under which conditions they are also classical solutions of the equations of motion. The supersymmetric configurations fall into two classes, depending on the timelike or null nature of the Killing vector constructed from Killing spinor bilinears. The timelike class configurations are essentially the ones found by Behrndt, Luest and Sabra, which exhaust this class and are the ones that include supersymmetric black holes. The null class configurations include pp-waves and cosmic strings.

  20. Molecular Fluoride-Bridged 3d-4f Complexes and Their Magnetic Properties

    DEFF Research Database (Denmark)

    Pedersen, K. S.; Bendix, J.

    2016-01-01

    trifluorides with very high lattice enthalpies, building block approaches are not limited to robust systems and use of labile transition metal fluoride complexes has met with unexpected success. The physical properties of fluoride-bridged 3d-4f systems are crucially dependent on coordination geometries, which...... be utilized efficiently in tailored synthesis of polynuclear complexes and extended structures. In particular, the strong affinity of the lanthanides for fluoride makes it a good choice for directed synthesis of mixed lanthanide-transition metal complexes. Despite the competition from formation of lanthanide...

  1. GIS 3D/4D per le reti tecnologiche sottosuolo (e soprasuolo

    Directory of Open Access Journals (Sweden)

    Andrea Deiana

    2016-10-01

    Full Text Available Organizations managing underground networks are asking, with growing strength, upgraded information systems and we can find several software/ hardware houses offering solutions for mapping these underground networks in order to visualize them. In this paper we try to show the 3D/4D GIS solutions by Skyline for underground networks' visualization and querying: one simply procedure for the visualization and a slightly complex one for alphanumeric data querying.

  2. Are natural scientists more masculine than humanists? The association patterns between 2D:4D ratio and field of study.

    Science.gov (United States)

    Kainz, Sarah; Weitzer, Jacob; Zingale, Stefania; Köllner, Johanna; Albrecht, Cornelia; Gaidora, Angelika; Rudorfer, Marie-Theres; Nürnberger, Anna; Kirchengast, Sylvia

    2018-06-11

    Natural sciences are still considered as typical male fields, while humanities are interpreted as typical female topics. Economic, social but also biological factors are discussed to influence the choice of study field. In the present study, the impact of prenatal sex hormone exposure - estimated by 2D:4D ratio - on the choice of study field was analyzed. Two hundred Viennese students between the ages 18 and 28 years were enrolled. Lengths of the index finger and the ring finger were measured directly from the hand of the participants. 2D:4D ratios were calculated. Male and female students differed significantly in 2D:4D ratio. As expected, female students showed significantly higher 2D:4D ratios than their male counterparts ( p < 0.001). Male scientists and male humanists differed significantly in 2D:4D ratio. The 2D:4D of male humanists was significantly higher than that of scientists ( p = 0.037). Female scientists and female humanists however, did not differ significantly in 2D:4D ratio. Both showed a typical female 2D:4D ratio. This was also true of male humanists. Consequently low prenatal androgen exposure may be associated with the choice of humanities among male students.

  3. Potential role of TBC1D4 in enhanced post-exercise insulin action in human skeletal muscle

    DEFF Research Database (Denmark)

    Treebak, Jonas Thue; Frøsig, Christian; Pehmøller, Christian

    2009-01-01

    .01). However, TBC1D4 phosphorylation on Ser-318, Ser-341, Ser-588 and Ser-751 was higher in the previously exercised leg, both in the absence and in the presence of insulin (p power = 0.39). 14-3-3 binding capacity for TBC1D4 increased equally (p

  4. Synthesis of Polysiloxanes In Microemulsion Via ring opening of D4

    Directory of Open Access Journals (Sweden)

    Liu Jiesheng

    2016-07-01

    Full Text Available Polydimethylsiloxane (PDMS has been synthesized by ring-opening polymerization of octamethylcyclotetrasiloxane (D4 in microemulsion with acidic catalyst. The structure and properties of microemulsion were characterized by Transmission Electron Microscopy (TEM, Fourier Transform Infrared Spectroscopy (FT-IR, Photo Correlation Spectroscopy (PCS. The effect of the variation in pH value, amount of catalyst, emulsifier and monomer dropping rate on the properties of microemulsion were investigated and discussed. The results showed that the particle size of the latex becomes smaller, and the distribution size becomes wider with increasing the content of catalyst and emulsifier. When pH value changed, the reaction rate of ring-opening of D4 was faster with strong acid than that under the weak acid condition. The emulsification of 2 % OP-10 (Alkylphenol polyoxyethylene ether and 3.0% DBSA (Dodecyl benzenesulfonic acid reached to equilibrium in microemulsion. As the amount of OP-10 increases, the size of particles lowered and their corresponding  distribution widened. It is observed that emulsifier (OP-10 does not affect the transparency of the microemulsion in the case of the application of DBSA. As the monomer dropping time increased, the grain size diminished and the size distribution widened. PCS results showed that the smallest particle size was around 20nm. Taking into account of the stability of the microemulsions, the dropping time of the monomer was around 30 min.

  5. Modeling Bottom-Up Visual Attention Using Dihedral Group D4 §

    Directory of Open Access Journals (Sweden)

    Puneet Sharma

    2016-08-01

    Full Text Available In this paper, first, we briefly describe the dihedral group D 4 that serves as the basis for calculating saliency in our proposed model. Second, our saliency model makes two major changes in a latest state-of-the-art model known as group-based asymmetry. First, based on the properties of the dihedral group D 4 , we simplify the asymmetry calculations associated with the measurement of saliency. This results is an algorithm that reduces the number of calculations by at least half that makes it the fastest among the six best algorithms used in this research article. Second, in order to maximize the information across different chromatic and multi-resolution features, the color image space is de-correlated. We evaluate our algorithm against 10 state-of-the-art saliency models. Our results show that by using optimal parameters for a given dataset, our proposed model can outperform the best saliency algorithm in the literature. However, as the differences among the (few best saliency models are small, we would like to suggest that our proposed model is among the best and the fastest among the best. Finally, as a part of future work, we suggest that our proposed approach on saliency can be extended to include three-dimensional image data.

  6. The 'donations for decreased ALT (D4D)' prosocial behavior incentive scheme for NAFLD patients.

    Science.gov (United States)

    Sumida, Yoshio; Yoshikawa, Toshikazu; Tanaka, Saiyu; Taketani, Hiroyoshi; Kanemasa, Kazuyuki; Nishimura, Tekeshi; Yamaguchi, Kanji; Mitsuyoshi, Hironori; Yasui, Kohichiroh; Minami, Masahito; Naito, Yuji; Itoh, Yoshito

    2014-12-01

    Physicians often experience difficulties in motivating patients with non-alcoholic fatty liver disease (NAFLD) to undergo lifestyle changes. The aim of this study is to examine whether 'Donations for Decreased alanine aminotransferase (ALT)' (D4D) prosocial behavior incentive can serve as an effective intrinsic motivational factor in comparison with conventional dietary and exercise intervention alone for NAFLD patients. Twenty-five NAFLD patients with elevated ALT were randomly assigned to a control group that received conventional dietary and exercise intervention alone, or a donation group whereby, as an incentive, we would make a monetary donation to the United Nations World Food Programme (WFP) based on the decrease in their ALT levels achieved over 12 weeks, in addition to receiving control intervention. In a donation group, we would donate US$1 to the WFP for every 1 IU/l of decrease in their ALT levels. There were no differences of pre-treatment clinical characteristics between the two groups. Significant reductions of ALT levels were achieved only in a donation group, although post-treatment ALT levels were not different between the two groups. These patients raised a total of $316 for the WFP. Promoting patients' intrinsic motivation by incorporating 'D4D' prosocial behavior incentive into conventional dietary and exercise intervention may provide a means to improve NAFLD. © The Author 2013. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Threshold photoelectron--photonion coincidence mass spectrometric study of ethylene and ethylene-d4

    International Nuclear Information System (INIS)

    Stockbauer, R.; Inghram, M.G.

    1975-01-01

    Experimental curves have been obtained for the fragmentation of ethylene and ethylene-d 4 ions as a function of the internal energy of those ions using threshold photoelectron--photoion coincidence mass spectrometry. The results are compared with the previous results of photoionization mass spectrometry, He I photoelectron--photoion coicidence, charge exchange experiments, and with quasiequilibrium theory (QET) calculations. The discrepancies between results of these previous experiments and QET calculations do not appear in the present data. It is suggested that ion--molecule reactions competing with charge exchange has led to erroneous conclusions in the interpretation of the charge exchange data. It is concluded that QET does describe the fragmentation of ethylene and ethylene-d 4 within the limits of the data and calculations available. The secondary ion fragmentation C 2 H 4 + → C 2 H 3 + +H → C 2 H 2 + +2H is discussed in detail with regard to the C 2 H 3 + fragment ion internal energy distribution

  8. Chronic Stressors and Adolescents' Externalizing Problems: Genetic Moderation by Dopamine Receptor D4. The TRAILS Study.

    Science.gov (United States)

    Zandstra, Anna Roos E; Ormel, Johan; Hoekstra, Pieter J; Hartman, Catharina A

    2018-01-01

    The existing literature does not provide consistent evidence that carriers of the Dopamine D4 Receptor 7-repeat allele are more sensitive to adverse environmental influences, resulting in enhanced externalizing problems, compared to noncarriers. One explanation is that the adverse influences examined in prior studies were not severe, chronic, or distressing enough to reveal individual differences in sensitivity reflected by DRD4-7R. This study examined whether the 7-repeat allele moderated the association between chronic stressors capturing multiple stressful aspects of individuals' lives and externalizing problems in adolescence. We expected that chronic stressor levels would be associated with externalizing levels only in 7-repeat carriers. Using Linear Mixed Models, we analyzed data from 1621 Dutch adolescents (52.2% boys), obtained in three measurement waves (mean age approximately 11, 13.5, and 16 years) from the TRacking Adolescents' Individual Lives Survey (TRAILS) population-based birth cohort and the parallel clinic-referred cohort. Across informants, we found that higher levels of chronic stressors were related to higher externalizing levels in 7-repeat carriers but not in noncarriers, as hypothesized. Although previous studies on the 7-repeat allele as a moderator of environmental influences on adolescents' externalizing problems have not convincingly demonstrated individual differences in sensitivity to adverse environmental influences, our findings suggest that adolescent carriers of the Dopamine D4 Receptor 7-repeat allele are more sensitive to chronic, multi-context stressors than noncarriers.

  9. Presidential address: distinction or extinction.

    Science.gov (United States)

    Pressman, Barry D

    2008-10-01

    Despite its continuing scientific successes in imaging, radiology as a specialty is faced with a very difficult and competitive environment. Nonradiologists are more and more interested in vertically integrating imaging into their practices, while teleradiology and picture archiving and communication systems are resulting in the greater isolation of radiologists. Commoditization is a realistic and devastating threat to the survival and professionalism of the specialty. To remain viable as a specialty, radiologists must elevate their practice by subspecializing, becoming more involved with clinical care, and actively interacting with patients and referring clinicians. Distinction will prevent extinction.

  10. Beta-Adrenergic Receptor Activation during Distinct Patterns of Stimulation Critically Modulates the PKA-Dependence of LTP in the Mouse Hippocampus

    Science.gov (United States)

    Gelinas, Jennifer N.; Tenorio, Gustavo; Lemon, Neal; Abel, Ted; Nguyen, Peter V.

    2008-01-01

    Activation of Beta-adrenergic receptors (Beta-ARs) enhances hippocampal memory consolidation and long-term potentiation (LTP), a likely mechanism for memory storage. One signaling pathway linked to Beta-AR activation is the cAMP-PKA pathway. PKA is critical for the consolidation of hippocampal long-term memory and for the expression of some forms…

  11. Early nucleoside reverse transcriptase inhibitors for the treatment of HIV: a brief history of stavudine (D4T) and its comparison with other dideoxynucleosides.

    Science.gov (United States)

    Martin, John C; Hitchcock, Michael J M; De Clercq, Erik; Prusoff, William H

    2010-01-01

    The occasion of this 25th anniversary issue encouraged us to reminisce about the important history of the discovery of the dideoxynucleoside analogues for the treatment of HIV/AIDS and to chronicle our thoughts about a particular exciting and rewarding period of our scientific careers. Following the identification of the anti-HIV activity of zidovudine (AZT), we participated in the urgent quest to discover optimal treatments of HIV infection and AIDS. A number of previously synthesized nucleoside analogues were comparatively evaluated, and stavudine (D4T) emerged as a promising candidate for development. Following clinical evaluation, D4T became a mainstay of the initial antiretroviral combination therapy, prolonging and saving numerous lives. It has only recently been supplanted by better-tolerated treatments. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, vol. 85, issue 1, 2010. Copyright 2009 Elsevier B.V. All rights reserved.

  12. Activity-Based Anorexia Reduces Body Weight without Inducing a Separate Food Intake Microstructure or Activity Phenotype in Female Rats—Mediation via an Activation of Distinct Brain Nuclei

    Science.gov (United States)

    Scharner, Sophie; Prinz, Philip; Goebel-Stengel, Miriam; Kobelt, Peter; Hofmann, Tobias; Rose, Matthias; Stengel, Andreas

    2016-01-01

    Anorexia nervosa (AN) is accompanied by severe somatic and psychosocial complications. However, the underlying pathogenesis is poorly understood, treatment is challenging and often hampered by high relapse. Therefore, more basic research is needed to better understand the disease. Since hyperactivity often plays a role in AN, we characterized an animal model to mimic AN using restricted feeding and hyperactivity. Female Sprague-Dawley rats were divided into four groups: no activity/ad libitum feeding (ad libitum, AL, n = 9), activity/ad libitum feeding (activity, AC, n = 9), no activity/restricted feeding (RF, n = 12) and activity/restricted feeding (activity-based anorexia, ABA, n = 11). During the first week all rats were fed ad libitum, ABA and AC had access to a running wheel for 24 h/day. From week two ABA and RF only had access to food from 9:00 to 10:30 a.m. Body weight was assessed daily, activity and food intake monitored electronically, brain activation assessed using Fos immunohistochemistry at the end of the experiment. While during the first week no body weight differences were observed (p > 0.05), after food restriction RF rats showed a body weight decrease: −13% vs. day eight (p 0.05). Similarly, the daily physical activity was not different between AC and ABA (p > 0.05). The investigation of Fos expression in the brain showed neuronal activation in several brain nuclei such as the supraoptic nucleus, arcuate nucleus, locus coeruleus and nucleus of the solitary tract of ABA compared to AL rats. In conclusion, ABA combining physical activity and restricted feeding likely represents a suited animal model for AN to study pathophysiological alterations and pharmacological treatment options. Nonetheless, cautious interpretation of the data is necessary since rats do not voluntarily reduce their body weight as observed in human AN. PMID:27826222

  13. Activity-based anorexia reduces body weight without inducing a separate food intake microstructure or activity phenotype in female rats – mediation via an activation of distinct brain nuclei

    Directory of Open Access Journals (Sweden)

    Sophie Scharner

    2016-10-01

    Full Text Available Anorexia nervosa (AN is accompanied by severe somatic and psychosocial complications. However, the underlying pathogenesis is poorly understood, treatment is challenging and often hampered by high relapse. Therefore, more basic research is needed to better understand the disease. Since hyperactivity often plays a role in AN, we characterized an animal model to mimic AN using restricted feeding and hyperactivity. Female Sprague-Dawley rats were divided into four groups: no activity/ad libitum feeding (ad libitum, AL, n=9, activity/ad libitum feeding (activity, AC, n=9, no activity/restricted feeding (RF, n=12 and activity/restricted feeding (activity-based anorexia, ABA, n=11. During the first week all rats were fed ad libitum, ABA and AC had access to a running wheel for 24h/d. From week two ABA and RF only had access to food from 9:00-10:30 am. Body weight was assessed daily, activity and food intake monitored electronically, brain activation assessed using Fos immunohistochemistry at the end of the experiment. While during the first week no body weight differences were observed (p>0.05, after food restriction RF rats showed a body weight decrease: -13% vs. day eight (p0.05. Similarly, the daily physical activity was not different between AC and ABA (p>0.05. The investigation of Fos expression in the brain showed neuronal activation in several brain nuclei such as the supraoptic nucleus, arcuate nucleus, locus coeruleus and nucleus of the solitary tract of ABA compared to AL rats. In conclusion, ABA combining physical activity and restricted feeding likely represents a suited animal model for AN to study pathophysiological alterations and pharmacological treatment options. Nonetheless, cautious interpretation of the data is necessary since rats do not voluntarily reduce their body weight as observed in human AN.

  14. The 2D:4D Marker and Different Forms of Internet Use Disorder

    Directory of Open Access Journals (Sweden)

    Marko Müller

    2017-11-01

    Full Text Available Internet use disorder (IUD presents a growing problem worldwide. Among others, it manifests in loss of control over Internet usage and social problems due to problematic Internet use. Although IUD currently is not an official diagnosis in DSM-5 or ICD-10, mounting evidence suggests that IUD indeed could be categorized as a behavioral addiction. On a systemic neuroscientific level, IUD is well characterized and dysfunctions in the fronto-striatal-limbic loop have been observed in persons being afflicted with IUD. On a molecular level underlying these neural dysfunctions less is known. Therefore, the present research investigates the influence of prenatal testosterone as measured via the 2D:4D marker of the hand on IUD. Testosterone represents an interesting hormonal marker, because sex differences in IUD have been observed, e.g., males show higher tendencies toward Internet gaming disorder (IGD or females toward overusage of online social networks (both compared to the contrary sex. In N = 217 participants associations between the 2D:4D marker of the hand and both unspecified IUD and specific forms of IUD were investigated. It appeared that more female hands (right side; characterized by higher digit ratio of the index to the ring finger, i.e., >1, meaning lower prenatal testosterone were associated with lower IGD (rho = −0.17, p = 0.01, N = 211. This effect was driven by the facet of loss of control of Internet Gaming in the whole sample (rho = −0.20, p < 0.01, N = 211 and the female subsample (rho = −0.20, p = 0.02, N(f = 137. Aside from this, a negative association appeared between the facet of loss of control of generalized IUD and the right digit ratio in males underlining earlier work. In sum, the present work demonstrates that the 2D:4D marker is an interesting marker for Internet addiction and can be easily included as a biomarker to understand the biological underpinnings of Internet (over-usage.

  15. A subordinate status position increases the present value of financial resources for low 2D:4D men.

    Science.gov (United States)

    Millet, Kobe; Dewitte, Siegfried

    2008-01-01

    It has been suggested that the ratio of the length of the 2nd and 4th fingers (digit ratio or 2D:4D) is related to prenatal testosterone with lower ratios thought to be influenced by higher prenatal testosterone levels. Accordingly, low 2D:4D has been associated to a number of fitness-related factors, such as high status in competitive sports and in music. Recent evidence suggests that 2D:4D is also related to economic decision making. We combine both streams of research in the present paper. In two studies we manipulated status in two different ways. We found that a subordinate position raises discount rates, consistent with the reasoning that the present utility of money is higher for men in this position. Moreover, the effect was more pronounced for men with a low 2D:4D. There was a significant negative relationship between 2D:4D and level of discounting in a subordinate status position, but no significant relationship emerged in the dominant status position. Our studies add evidence to the recent line of research associating digit ratio and economic decision making. Moreover, our studies show that future 2D:4D research should focus on plausible interactions between 2D:4D and context cues rather than on linear relations. (c) 2007 Wiley-Liss, Inc.

  16. Human mesenchymal stem cells generate a distinct pericellular zone of MMP activities via binding of MMPs and secretion of high levels of TIMPs.

    Science.gov (United States)

    Lozito, Thomas P; Jackson, Wesley M; Nesti, Leon J; Tuan, Rocky S

    2014-02-01

    Mesenchymal stem cells (MSCs) are attractive candidates for inclusion in cell-based therapies by virtue of their abilities to home to wound sites. However, in-depth characterization of the specific effects of MSCs on their microenvironments is needed to realize their full therapeutic potentials. Furthermore, since MSCs of varying properties can be isolated from a diverse spectrum of tissues, a strategic and rational approach in MSC sourcing for a particular application has yet to be achieved. For example, MSCs that activate their proteolytic environments may promote tissue remodeling, while those from different tissue sources may inhibit proteases and promote tissue stabilization. This study attempts to address these issues by analyzing MSCs isolated from three adult tissue sources in terms of their effects on their proteolytic microenvironments. Human bone marrow, adipose, and traumatized muscle derived MSCs were compared in their soluble and cellular-associated MMP components and activity. For all types of MSCs, MMP activity associated with the cell surface, but activity levels and MMP profiles differed with tissue source. All MSC types bound exogenous active MMPs at their surfaces. MSCs were also able to activate exogenous proMMP-2 and proMMP-13. This is in marked contrast to the MSC soluble compartment, which strongly inhibited MMPs via endogenous TIMPs. The exact TIMP used to inhibit the exogenous MMP differed with MSC type. Thus, MSCs saturate their environment with both MMPs and TIMPs. Since they bind and activate MMPs at their surfaces, the net result is a very controlled pericellular localization of MMP activities by MSCs. © 2013.

  17. Distinct Roles for JNK and IKK Activation in Agouti-Related Peptide Neurons in the Development of Obesity and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Eva Tsaousidou

    2014-11-01

    Full Text Available Activation of c-Jun N-terminal kinase 1 (JNK1- and inhibitor of nuclear factor kappa-B kinase 2 (IKK2-dependent signaling plays a crucial role in the development of obesity-associated insulin and leptin resistance not only in peripheral tissues but also in the CNS. Here, we demonstrate that constitutive JNK activation in agouti-related peptide (AgRP-expressing neurons of the hypothalamus is sufficient to induce weight gain and adiposity in mice as a consequence of hyperphagia. JNK activation increases spontaneous action potential firing of AgRP cells and causes both neuronal and systemic leptin resistance. Similarly, activation of IKK2 signaling in AgRP neurons also increases firing of these cells but fails to cause obesity and leptin resistance. In contrast to JNK activation, IKK2 activation blunts insulin signaling in AgRP neurons and impairs systemic glucose homeostasis. Collectively, these experiments reveal both overlapping and nonredundant effects of JNK- and IKK-dependent signaling in AgRP neurons, which cooperate in the manifestation of the metabolic syndrome.

  18. WIMSCORE, 2-Group Constant from WIMS-D/4 for Programs TDB, TRITON, CITATION

    International Nuclear Information System (INIS)

    Bartal, Yair

    1991-01-01

    1 - Description of program or function: The code processes the WIMS-D/4 binary output files for producing two-group microscopic Cross sections and macroscopic lattice cell constants (zone and cell macroscopic Cross sections, D, M, and K-infinity) in a more flexible Format needed for reactor burnup codes like CITATION, for reactor dynamics codes like NADYP-W and for other reactor codes. The purpose of the WIMSCORE-ENEA code is to facilitate the automation of data transfer between the cell calculation code WIMS and the diffusion-burnup codes. 2 - Method of solution: The code spatially homogenizes and group collapses the various Cross sections into two-group homogenized microscopic Cross sections using the flux per mesh for each energy group for WIMS multigroup lattice calculations. 3 - Restrictions on the complexity of the problem: None

  19. Meson thermalization by baryon injection in D4/D6 model

    Energy Technology Data Exchange (ETDEWEB)

    Rezaei, Z., E-mail: z.rezaei@aut.ac.ir [Department of Physics, Tafresh University, Tafresh 39518 79611 (Iran, Islamic Republic of); School of Particles and Accelerators, Institute for Research in Fundamental Sciences (IPM), P.O. Box 19395-5531, Tehran (Iran, Islamic Republic of)

    2016-12-15

    We study meson thermalization in a strongly coupled plasma of quarks and gluons using AdS/CFT duality technique. Four dimensional large-N{sub c} QCD is considered as a theory governing this quark–gluon plasma (QGP) and D4/D6-brane model is chosen to be its holographic dual theory. In order to investigate meson thermalization, we consider a time-dependent change of baryon number chemical potential. Thermalization in gauge theory side corresponds to horizon formation on the probe flavor brane in the gravity side. The gravitational dual theory is compactified on a circle that the inverse of its radius is proportional to energy scale of dual gauge theory. It is seen that increase of this energy scale results in thermalization time dilation. In addition we study the effect of magnetic field on meson thermalization. It will be seen that magnetic field also prolongs thermalization process by making mesons more stable.

  20. Meson thermalization by baryon injection in D4/D6 model

    International Nuclear Information System (INIS)

    Rezaei, Z.

    2016-01-01

    We study meson thermalization in a strongly coupled plasma of quarks and gluons using AdS/CFT duality technique. Four dimensional large-N_c QCD is considered as a theory governing this quark–gluon plasma (QGP) and D4/D6-brane model is chosen to be its holographic dual theory. In order to investigate meson thermalization, we consider a time-dependent change of baryon number chemical potential. Thermalization in gauge theory side corresponds to horizon formation on the probe flavor brane in the gravity side. The gravitational dual theory is compactified on a circle that the inverse of its radius is proportional to energy scale of dual gauge theory. It is seen that increase of this energy scale results in thermalization time dilation. In addition we study the effect of magnetic field on meson thermalization. It will be seen that magnetic field also prolongs thermalization process by making mesons more stable.

  1. Meson thermalization by baryon injection in D4/D6 model

    Science.gov (United States)

    Rezaei, Z.

    2016-12-01

    We study meson thermalization in a strongly coupled plasma of quarks and gluons using AdS/CFT duality technique. Four dimensional large-Nc QCD is considered as a theory governing this quark-gluon plasma (QGP) and D4/D6-brane model is chosen to be its holographic dual theory. In order to investigate meson thermalization, we consider a time-dependent change of baryon number chemical potential. Thermalization in gauge theory side corresponds to horizon formation on the probe flavor brane in the gravity side. The gravitational dual theory is compactified on a circle that the inverse of its radius is proportional to energy scale of dual gauge theory. It is seen that increase of this energy scale results in thermalization time dilation. In addition we study the effect of magnetic field on meson thermalization. It will be seen that magnetic field also prolongs thermalization process by making mesons more stable.

  2. Bronchial effects of leukotriene D4 inhalation in normal human lung

    DEFF Research Database (Denmark)

    Bisgaard, H; Groth, S

    1987-01-01

    airways in asthmatic patients out of attack. LTD4 caused a dose-dependent obstruction of the airways as measured by partial flow-volume curves and volume of trapped gas, yet only minor changes in forced expiratory volume in 1 s (FEV1) and peak expiratory flow rate. LTD4 was 1900-7000 times more potent......The aim of the study was to investigate whether inhaled leukotriene (LT) D4 could mimic the characteristics of asthmatic patients after allergen-induced attack, i.e. a prolonged subclinical bronchial obstruction, an increased reactivity of the airways and a late reaction. The effects of LTD4 were...... than histamine. LTD4 inhalations were almost symptomless as opposed to the irritative and dyspnoeic symptoms seen after inhalation of histamine. The time duration for the induced change in partial flow-volume curves was the same for the two drugs. Approximately 30 min elapsed until the bronchial...

  3. Series of chiral interpenetrating 3d-4f heterometallic MOFs: Luminescent sensors and magnetic properties

    Science.gov (United States)

    Zhang, Xiaolei; Chen, Chen; Liu, Xiaoli; Gao, Peng; Hu, Ming

    2017-09-01

    Series of chiral 3d-4f heterometallic MOFs based on a multidentate terpyridyl carboxylic acid ligand have been synthesized under the solvothermal conditions, namely, [LnZnL(CO3)2(H2O)]n (Ln = Eu (1), Gd (2), Dy (3), Ho (4), Er (5), Tm (6), Yb (7), Lu (8)) (HL = 4‧-(4-carboxyphenyl)-2,2‧:6‧,2″-terpyridine). Compounds 1-8 were structurally characterized by the elemental analyses, infrared spectra, and single crystal X-ray diffractions. Compounds 1-8 exhibit the chiral interpenetrating 3D frameworks. Interestingly, 1 can serve as the luminescent sensor to detect nitrobenzene molecules with high sensitivity. The investigations on CD spectra of single crystals clearly assigned the Cotton effect, indicating that there exist two chiral enantiomers of 1-8 in the course of crystallization. The magnetic properties of 2 and 7 were exploited, respectively.

  4. New ENDF/B-V nuclear data library for WIMS-D4M

    International Nuclear Information System (INIS)

    Deen, J.R.; Woodruff, W.L.; Costescu, C.I.

    1994-01-01

    A new 69-group 96-material library has been created for use in WIMS-D4M. The latest SUN version of NJOY (91.27) was used to generate the ENDF/B-V-based cross-section library. The library also includes ENDF/B-V based fission yields, energy fission and energy per capture data. The upper energy boundary has been extended from 10 to 20 MeV in order to model high energy neutron reactions. Additional fuel and moderator temperatures have been included to better predict temperature coefficients. More excess potential scattering points have been added to increase the accuracy of self-shielded resonance cross-sections. Several benchmark comparisons have been made to validate the new library. (author)

  5. Chiral vortical effect from the compactified D4-branes with smeared D0-brane charge

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Chao; Chen, Yidian [Institute of High Energy Physics, Chinese Academy of Sciences,Beijing 100049 (China); Huang, Mei [Institute of High Energy Physics, Chinese Academy of Sciences,Beijing 100049 (China); University of Chinese Academy of Sciences,Beijing 100049 (China); Theoretical Physics Center for Science Facilities, Chinese Academy of Sciences,Beijing 100049 (China)

    2017-03-15

    By using the boundary derivative expansion formalism of fluid/gravity correspondence, we study the chiral vortical effect from the compactified D4-branes with smeared D0-brane charge. This background corresponds to a strongly coupled, nonconformal relativistic fluid with a conserved vector current. The presence of the chiral vortical effect is induced by the addition of a Chern-Simons term in the bulk action. Except that the non-dissipative anomalous viscous coefficient and the sound speed rely only on the chemical potential, most of the other thermal and hydrodynamical quantities of the first order depend both on the temperature and the chemical potential. According to our result, the way that the chiral vortical effect coefficient depends on the chemical potential seems irrelevant with whether the relativistic fluid is conformal or not. Stability analysis shows that this anomalous relativistic fluid is stable and the doping of the smeared D0-brane charge will slow down the sound speed.

  6. Synthesis and magnetic properties of heteronuclear 3d-4f compound

    International Nuclear Information System (INIS)

    Cristovao, B.; Ferenc, W.

    2007-01-01

    A novel heteronuclear 3d-4f compound having formula NdCu 3 L 3 ·13H 2 O (where H 3 L = Schiff base derived from 5-bromosalicylaldehyde and glycylglycine and L 3 = C 11 H 8 N 2 O 4 Br) was obtained. It was characterized by elemental and thermal analyses and magnetic measurements. The Cu(II)-Nd(III) compound is stable up to 323 K. During dehydration process the water molecules are lost in two stages. The magnetic susceptibility data for this complex change with temperature according to the Curie-Weiss law with Θ = -35 K. The magnetic moment values decrease from 5.00μ B at 303 K to 4.38μB at 76 K. (author)

  7. Coupling of Yang-Mills to N=4, d=4 supergravity

    International Nuclear Information System (INIS)

    Bergshoeff, E.; Koh, I.G.; Sezgin, E.

    1985-01-01

    We couple N=4, d=4 supersymmetric Yang-Mills theory to supergravity. The scalars of the theory parametrize the coset (SO(n,6)/[SO(n)xSO(6)])xSU(1,1)/U(1)). Keeping the composite local SO(n)xSO(6)xU(1) invariance intact, we gauge an (n+6) parameter subgroup of SO(n,6) which is either (i) SU(2)xSU(2)xH(dim H=n), (ii) SO(4,1)xH(dim H=n-4) or (iii) SO(6,1)xH(dim H=n-15). In all these cases the theory has an indefinite potential. (orig.)

  8. Covariant quantization of the d=4 Brink-Schwarz superparticle using Lorentz harmonics

    International Nuclear Information System (INIS)

    Zima, V.G.; Fedoryuk, S.A.

    1995-01-01

    Covariant first and second quantizations of the free d=4 massless superparticle are implemented with the introduction of purely gauge auxiliary spinor Lorentz harmonics. It is shown that the general solution of the condition of masslessness is a sum of two independent chiral superfields with each of them corresponding to finite superspin. A translationally covariant, in general bijective correspondence between harmonic and massless superfields is constructed. By calculation of the commutation function it is shown that in the considered approach only harmonic fields with the correct connection between spin and statistics and with integer negative homogeneity index satisfy the microcausality condition. It is emphasized that the harmonic fields that arise are reducible at integer points. The index spinor technique is used to describe infinite-component fields of finite spin; the equations of motion of such fields are obtained, and for them Weinberg's theorem on the connection between massless helicity particles and the type of nongauge field that describes them is generalized

  9. Coupling of Yang-Mills to N=4, d=4 supergravity

    International Nuclear Information System (INIS)

    Bergshoeff, E.; Koh, I.G.; Sezgin, E.

    1985-01-01

    We couple N=4, d=4 supersymmetric Yang-Mills theory to supergravity. The scalars of the theory parametrize the coset ((SO(n,6)/SO(n)xSO(6))x((SU(1,1)/U(1)). Keeping the composite local SO(n)xSO(6)xU(1) invariance intact, we gauge an (n+6) parameter subgroup of SO(n,6) which is either (i) SU(2)xSU(2)xH (dim H=n), (ii) SO(4,1)xH (dim H=n-4) or (iii) SO(6,1)xH (dim H=n-15). In all these cases the theory has an indefinite potential. (author)

  10. A tetranucleotide repeat (D4S1652) is linked to facioscapulohumeral dystrophy and shows no linkage disequilibrium with the disease

    Energy Technology Data Exchange (ETDEWEB)

    Mathews, K.D.; Bailey, H.L.; Mills, K.A. [and others

    1994-09-01

    Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant dystrophy which is associated with a deletion in a subtelomeric repeat element on 4q35. The gene has not yet been identified. The probe detecting this deletion (D4F104S1) is not chromosome 4-specific, and at least one large family has been identified which is not linked to chromosome 4. Thus, persymptomatic/prenatal diagnosis can only be provided to families that are proven to be chromosome 4-linked or where a new mutation is demonstrated. The markers available to demonstrate linkage to chromosome 4, D4S139, D4S163, and D4F35S1, are VNTRs. We have used D4S1652, a tetranucleotide repeat recently identified by the Cooperative Human Linkage Center, in our FSHD families. We found it is completely linked to the 4q35 VNTRs and to the disease phenotype. Physical mapping, using radiation hybrids and somatic cell hybrids, places D4S1652 between D4S139, an interval of approximately 1 Mb. We have used D4S1652 to look for linkage disequilibrium in our FSHD patient population. This result is of interest because of our hypothesis that the deletion in the subtelomeric repeat element alters transcription of a more proximal gene through a position effect. Previously available markers have been unsatisfactory for this experiment because of difficulty comparing numerous VNTR alleles across families. We observed 4, easily distinguished, D4S1652 alleles in our families. We studied 14 chromosomes associated with disease phenotype and 55 chromosomes from nontransmitting parents. We found no evidence for linkage disequilibrium ({chi}{sup 2}=1.313, nonsignificant). This result will need confirmation with a larger patient population, but is consistent with the clinical observation that there is a high rate of a new mutation in this disorder.

  11. Value of digit ratio 2D:4D, a biomarker of prenatal hormone exposure, is stable across the menstrual cycle.

    Science.gov (United States)

    Klimek, Magdalena; Marcinkowska, Urszula M; Jasienska, Grazyna

    2017-07-01

    Digit ratio (2D:4D) is used as a marker of prenatal hormone exposure and, consequently, as a predictor of many characteristics throughout a woman's lifespan. A previous study has suggested that values of 2D:4D vary across menstrual cycles and further questioned the reliability of a single measurement of 2D:4D among cycling women, while another study failed to confirm these results. However, these studies estimated the timing of cycle phases based on a date of menstruation reported by participants and also had small sample sizes. For our study, we evaluated potential changes in 2D:4D values across a menstrual cycle in a group of women among whom the phases of the menstrual cycle were determined by hormonal (luteinizing hormone based) ovulation tests. We studied 32 naturally cycling women aged 22-37 from rural Poland. Lengths of second and fourth digits were measured based on scans of both hands taken three times (i.e. in the follicular phase, peri-ovulatory phase and luteal phase of the cycle) for each participant. No differences in 2D:4D value across the menstrual cycle were detected either when right-hand, left-hand, and mean 2D:4D for both hands were analysed, nor when difference in the 2D:4D value between hands (D left-right ) was evaluated. We documented that 2D:4D is independent of the phase of the menstrual cycle and these findings suggest that among naturally cycling women, a value of 2D:4D can be reliably obtained from measurements taken during any day of the menstrual cycle. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Increasing maternal body mass index is associated with systemic inflammation in the mother and the activation of distinct placental inflammatory pathways.

    Science.gov (United States)

    Aye, Irving L M H; Lager, Susanne; Ramirez, Vanessa I; Gaccioli, Francesca; Dudley, Donald J; Jansson, Thomas; Powell, Theresa L

    2014-06-01

    Obese pregnant women have increased levels of proinflammatory cytokines in maternal circulation and placental tissues. However, the pathways contributing to placental inflammation in obesity are largely unknown. We tested the hypothesis that maternal body mass index (BMI) was associated with elevated proinflammatory cytokines in maternal and fetal circulations and increased activation of placental inflammatory pathways. A total of 60 women of varying pre-/early pregnancy BMI, undergoing delivery by Cesarean section at term, were studied. Maternal and fetal (cord) plasma were collected for analysis of insulin, leptin, IL-1beta, IL-6, IL-8, monocyte chemoattractant protein (MCP) 1, and TNFalpha by multiplex ELISA. Activation of the inflammatory pathways in the placenta was investigated by measuring the phosphorylated and total protein expression of p38-mitogen-activated protein kinase (MAPK), c-Jun-N-terminal kinase (JNK)-MAPK, signal transducer-activated transcription factor (STAT) 3, caspase-1, IL-1beta, IkappaB-alpha protein, and p65 DNA-binding activity. To determine the link between activated placental inflammatory pathways and elevated maternal cytokines, cultured primary human trophoblast (PHT) cells were treated with physiological concentrations of insulin, MCP-1, and TNFalpha, and inflammatory signaling analyzed by Western blot. Maternal BMI was positively correlated with maternal insulin, leptin, MCP-1, and TNFalpha, whereas only fetal leptin was increased with BMI. Placental phosphorylation of p38-MAPK and STAT3, and the expression of IL-1beta protein, were increased with maternal BMI; phosphorylation of p38-MAPK was also correlated with birth weight. In contrast, placental NFkappaB, JNK and caspase-1 signaling, and fetal cytokine levels were unaffected by maternal BMI. In PHT cells, p38-MAPK was activated by MCP-1 and TNFalpha, whereas STAT3 phosphorylation was increased following TNFalpha treatment. Maternal BMI is associated with elevated maternal

  13. Increasing Maternal Body Mass Index Is Associated with Systemic Inflammation in the Mother and the Activation of Distinct Placental Inflammatory Pathways1

    Science.gov (United States)

    Aye, Irving L.M.H.; Lager, Susanne; Ramirez, Vanessa I.; Gaccioli, Francesca; Dudley, Donald J.; Jansson, Thomas; Powell, Theresa L.

    2014-01-01

    ABSTRACT Obese pregnant women have increased levels of proinflammatory cytokines in maternal circulation and placental tissues. However, the pathways contributing to placental inflammation in obesity are largely unknown. We tested the hypothesis that maternal body mass index (BMI) was associated with elevated proinflammatory cytokines in maternal and fetal circulations and increased activation of placental inflammatory pathways. A total of 60 women of varying pre-/early pregnancy BMI, undergoing delivery by Cesarean section at term, were studied. Maternal and fetal (cord) plasma were collected for analysis of insulin, leptin, IL-1beta, IL-6, IL-8, monocyte chemoattractant protein (MCP) 1, and TNFalpha by multiplex ELISA. Activation of the inflammatory pathways in the placenta was investigated by measuring the phosphorylated and total protein expression of p38-mitogen-activated protein kinase (MAPK), c-Jun-N-terminal kinase (JNK)-MAPK, signal transducer-activated transcription factor (STAT) 3, caspase-1, IL-1beta, IkappaB-alpha protein, and p65 DNA-binding activity. To determine the link between activated placental inflammatory pathways and elevated maternal cytokines, cultured primary human trophoblast (PHT) cells were treated with physiological concentrations of insulin, MCP-1, and TNFalpha, and inflammatory signaling analyzed by Western blot. Maternal BMI was positively correlated with maternal insulin, leptin, MCP-1, and TNFalpha, whereas only fetal leptin was increased with BMI. Placental phosphorylation of p38-MAPK and STAT3, and the expression of IL-1beta protein, were increased with maternal BMI; phosphorylation of p38-MAPK was also correlated with birth weight. In contrast, placental NFkappaB, JNK and caspase-1 signaling, and fetal cytokine levels were unaffected by maternal BMI. In PHT cells, p38-MAPK was activated by MCP-1 and TNFalpha, whereas STAT3 phosphorylation was increased following TNFalpha treatment. Maternal BMI is associated with elevated

  14. Yang-Mills instantons sitting on a Ricci-flat worldspace of double D4-branes

    International Nuclear Information System (INIS)

    Kim, Hongsu; Yoon, Yongsung

    2001-01-01

    Thus far, there seem to be no complete criteria that can settle the issue as to what the correct generalization of the Dirac-Born-Infeld (DBI) action, describing the low-energy dynamics of the D-branes, to the non-Abelian case would be. According to recent suggestions, one might pass the issue of worldvolume solitons from an Abelian to non-Abelian setting by considering the stack of multiple, coincident D-branes and use it as a guideline to construct or censor the relevant non-Abelian version of the DBI action. In this spirit, here we are interested in the explicit construction of SU(2) Yang-Mills (YM) instanton solutions in the background geometry of two coincident probe D4-brane worldspaces, particularly when the metric of the target spacetime in which the probe branes are embedded is given by the Ricci-flat, magnetic extremal 4-brane solution in type IIA supergravity theory with its worldspace metric being given by that of TaubendashNewman-Unti-Tamburino (NUT) and Eguchi-Hanson solutions, the two best-known gravitational instantons. Then we demonstrate that, with this YM instanton-gravitational instanton configuration on the probe D4-brane worldvolume, the energy of the probe branes attains its minimum value and hence enjoys a stable state provided one employs Tseytlin's non-Abelian DBI action for the description of multiple probe D-branes. In this way, we support the arguments in the literature in favor of Tseytlin's proposal for the non-Abelian DBI action

  15. Characterization of the ER-Targeted Low Affinity Ca2+ Probe D4ER

    Directory of Open Access Journals (Sweden)

    Elisa Greotti

    2016-09-01

    Full Text Available Calcium ion (Ca2+ is a ubiquitous intracellular messenger and changes in its concentration impact on nearly every aspect of cell life. Endoplasmic reticulum (ER represents the major intracellular Ca2+ store and the free Ca2+ concentration ([Ca2+] within its lumen ([Ca2+]ER can reach levels higher than 1 mM. Several genetically-encoded ER-targeted Ca2+ sensors have been developed over the last years. However, most of them are non-ratiometric and, thus, their signal is difficult to calibrate in live cells and is affected by shifts in the focal plane and artifactual movements of the sample. On the other hand, existing ratiometric Ca2+ probes are plagued by different drawbacks, such as a double dissociation constant (Kd for Ca2+, low dynamic range, and an affinity for the cation that is too high for the levels of [Ca2+] in the ER lumen. Here, we report the characterization of a recently generated ER-targeted, Förster resonance energy transfer (FRET-based, Cameleon probe, named D4ER, characterized by suitable Ca2+ affinity and dynamic range for monitoring [Ca2+] variations within the ER. As an example, resting [Ca2+]ER have been evaluated in a known paradigm of altered ER Ca2+ homeostasis, i.e., in cells expressing a mutated form of the familial Alzheimer’s Disease-linked protein Presenilin 2 (PS2. The lower Ca2+ affinity of the D4ER probe, compared to that of the previously generated D1ER, allowed the detection of a conspicuous, more clear-cut, reduction in ER Ca2+ content in cells expressing mutated PS2, compared to controls.

  16. Evaluation of static physics performance of the jPET-D4 by Monte Carlo simulations

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, Tomoyuki [Allied Health Sciences, Kitasato University, Kitasato 1-15-1, Sagamihara, Kanagawa, 228-8555 (Japan); Yoshida, Eiji [Molecular Imaging Centre, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage, Chiba, 263-8555 (Japan); Kobayashi, Ayako [Graduate School of Human Health Sciences, Tokyo Metropolitan University, Arakawa, Tokyo, 116-8551 (Japan); Shibuya, Kengo [Molecular Imaging Centre, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage, Chiba, 263-8555 (Japan); Nishikido, Fumihiko [Molecular Imaging Centre, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage, Chiba, 263-8555 (Japan); Kobayashi, Tetsuya [Graduate School of Science and Technology, Chiba University, 1-33 Yayoi, Inage, Chiba, 263-8522 (Japan); Suga, Mikio [Graduate School of Science and Technology, Chiba University, 1-33 Yayoi, Inage, Chiba, 263-8522 (Japan); Yamaya, Taiga [Molecular Imaging Centre, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage, Chiba, 263-8555 (Japan); Kitamura, Keishi [Shimadzu Corporation, 1 Nishinokyo-kuwabara-cho, Nakagyo-ku, Kyoto, 604-8511 (Japan); Maruyama, Koichi [Allied Health Sciences, Kitasato University, Kitasato 1-15-1, Sagamihara, Kanagawa, 228-8555 (Japan); Murayama, Hideo [Molecular Imaging Centre, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage, Chiba, 263-8555 (Japan)

    2007-01-07

    The jPET-D4 is the first PET scanner to introduce a unique four-layer depth-of-interaction (DOI) detector scheme in order to achieve high sensitivity and uniform high spatial resolution. This paper compares measurement and Monte Carlo simulation results of the static physics performance of this prototype research PET scanner. Measurement results include single and coincidence energy spectra, point and line source sensitivities, axial sensitivity profile (slice profile) and scatter fraction. We use GATE (Geant4 application for tomographic emission) as a Monte Carlo radiation transport model. Experimental results are reproduced well by the simulation model with reasonable assumptions on characteristic responses of the DOI detectors. In a previous study, the jPET-D4 was shown to provide a uniform spatial resolution as good as 3 mm (FHWM). In the present study, we demonstrate that a high sensitivity, 11.3 {+-} 0.5%, is provided at the FOV centre. However, about three-fourths of this sensitivity is related to multiple-crystal events, for which some misidentification of the crystal cannot be avoided. Therefore, it is crucial to develop a more efficient way to identify the crystal of interaction and to reduce misidentification in order to make use of these high performance values simultaneously. We expect that effective sensitivity can be improved by replacing the GSO crystals with more absorptive crystals such as BGO and LSO. The results we describe here are essential to take full advantage of the next generation PET systems that have DOI recognition capability.

  17. 3d-4f {Co(II)3Ln(OR)4} Cubanes as Bio-Inspired Water Oxidation Catalysts.

    Science.gov (United States)

    Evangelisti, Fabio; Moré, René; Hodel, Florian; Luber, Sandra; Patzke, Greta Ricarda

    2015-09-02

    Although the {CaMn4O5} oxygen evolving complex (OEC) of photosystem II is a major paradigm for water oxidation catalyst (WOC) development, the comprehensive translation of its key features into active molecular WOCs remains challenging. The [Co(II)3Ln(hmp)4(OAc)5H2O] ({Co(II)3Ln(OR)4}; Ln = Ho-Yb, hmp = 2-(hydroxymethyl)pyridine) cubane WOC series is introduced as a new springboard to address crucial design parameters, ranging from nuclearity and redox-inactive promoters to operational stability and ligand exchange properties. The {Co(II)3Ln(OR)4} cubanes promote bioinspired WOC design by newly combining Ln(3+) centers as redox-inactive Ca(2+) analogues with flexible aqua-/acetate ligands into active and stable WOCs (max. TON/TOF values of 211/9 s(-1)). Furthermore, they open up the important family of 3d-4f complexes for photocatalytic applications. The stability of the {Co(II)3Ln(OR)4} WOCs under photocatalytic conditions is demonstrated with a comprehensive analytical strategy including trace metal analyses and solution-based X-ray absorption spectroscopy (XAS) investigations. The productive influence of the Ln(3+) centers is linked to favorable ligand mobility, and the experimental trends are substantiated with Born-Oppenheimer molecular dynamics studies.

  18. Increase in a distinct pulmonary macrophage subset possessing an antigen-presenting cell phenotype and in vitro APC activity following silica exposure

    International Nuclear Information System (INIS)

    Migliaccio, Christopher T.; Hamilton, Raymond F.; Holian, Andrij

    2005-01-01

    Silica inhalation results in chronic lung inflammation and fibrosis. While the role of the alveolar macrophage (AM) is considered key to the effects of silica on lung pathology, the etiology is not completely understood. Evidence suggests an increase in antigen presenting cell (APC) activity as a contributing factor to this process, as well as potential roles for both AM and interstitial macrophages (IM) in silicosis. In order to study the effects of crystalline silica on the APC activity of pulmonary macrophages, mice were exposed intranasally and changes in pulmonary macrophage populations were assessed using flow cytometry. Following intranasal instillation of silica, a significant increase in the APC activity of AM was observed, as well as a significant increase in a subset of IM expressing classic APC markers (MHC class II, CD11c). In addition, an in vitro system using bone marrow-derived macrophages (BMDM) was generated to assess the effects of silica on the APC activity of macrophages in vitro. Data using BMDM in the in vitro APC assay demonstrated a significant increase in APC activity following silica exposure, but not following exposure to saline or a control particle (TiO 2 ). Using a combination of in vivo and in vitro experiments, the current study describes a significant increase in an interstitial macrophage subset with an APC phenotype, as well as an increase in the APC activity of both AM and BMDM, as a direct result of exposure to crystalline silica. These studies suggest a specific mechanism, macrophage subset activation, by which crystalline silica exposure results in chronic pulmonary inflammation and, eventually, fibrosis

  19. Transcriptional switching by the MerR protein: Activation and repression mutants implicate distinct DNA and mercury(II) binding domains

    International Nuclear Information System (INIS)

    Shewchuk, L.M.; Helmann, J.D.; Ross, W.; Park, S.J.; Summers, A.O.; Walsh, C.T.

    1989-01-01

    Bacterial resistance to mercuric compounds is controlled by the MerR metalloregulatory protein. The MerR protein functions as both a transcriptional repressor and a mercuric ion dependent transcriptional activator. Chemical mutagenesis of the cloned merR structural gene has led to the identification of mutant proteins that are specifically deficient in transcriptional repression, activation, or both. Five mutant proteins have been overproduced, purified to homogeneity, and assayed for ability to dimerize, bind mer operator DNA, and bind mercuric ion. A mutation in the recognition helix of a proposed helix-turn-helix DNA binding motif (E22K) yields protein deficient in both activation and repression in vivo (a - r - ) and deficient in operator binding in vitro. In contrast, mutations in three of the four MerR cysteine residues are repression competent but activation deficient (a - r + ) in vivo. In vitro, the purified cysteine mutant proteins bind to the mer operator site with near wild-type affinity but are variable deficient in binding the in vivo inducer mercury(II) ion. A subset of the isolated proteins also appears compromised in their ability to form dimers at low protein concentrations. These data support a model in which DNA-bound MerR dimer binds one mercuric ion and transmits this occupancy information to a protein region involved in transcriptional activation

  20. Touch communicates distinct emotions.

    Science.gov (United States)

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

    2006-08-01

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

  1. Small and intermediate conductance Ca2+-activated K+ channels confer distinctive patterns of distribution in human tissues and differential cellular localisation in the colon and corpus cavernosum

    NARCIS (Netherlands)

    Chen, Mao Xiang; Gorman, Shelby A.; Benson, Bill; Singh, Kuljit; Hieble, J. Paul; Michel, Martin C.; Tate, Simon N.; Trezise, Derek J.

    2004-01-01

    The SK/IK family of small and intermediate conductance calcium-activated potassium channels contains four members, SK1, SK2, SK3 and IK1, and is important for the regulation of a variety of neuronal and non-neuronal functions. In this study we have analysed the distribution of these channels in

  2. Differential extracellular signal-regulated kinases 1 and 2 activation by the angiotensin type 1 receptor supports distinct phenotypes of cardiac myocytes

    DEFF Research Database (Denmark)

    Aplin, Mark; Christensen, Gitte Lund; Schneider, Mikael

    2007-01-01

    that phosphorylates p90 Ribosomal S6 Kinase, a ubiquitous and versatile mediator of ERK1/2 signal transduction. Moreover, the beta-arrestin2-dependent ERK1/2 signal supports intact proliferation of cardiac myocytes. In contrast to G(q)-activated ERK1/2, and in keeping with its failure to translocate to the nucleus...

  3. Assessment of the potential activity of major dietary compounds as selective estrogen receptor modulators in two distinct cell models for proliferation and differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Lecomte, Sylvain; Lelong, Marie; Bourgine, Gaëlle [Institut de Recherche en Santé-Environnement-Travail (IRSET), Inserm UMR 1085, Team Transcription, Environment and Cancer, University of Rennes 1, 9 Avenue du Pr Léon Bernard, 35000 Rennes (France); Efstathiou, Theo [Laboratoire Nutrinov, Technopole Atalante Champeaux, 8 rue Jules Maillard de la Gournerie, 35012 Rennes Cedex (France); Saligaut, Christian [Institut de Recherche en Santé-Environnement-Travail (IRSET), Inserm UMR 1085, Team Transcription, Environment and Cancer, University of Rennes 1, 9 Avenue du Pr Léon Bernard, 35000 Rennes (France); Pakdel, Farzad, E-mail: farzad.pakdel@univ-rennes1.fr [Institut de Recherche en Santé-Environnement-Travail (IRSET), Inserm UMR 1085, Team Transcription, Environment and Cancer, University of Rennes 1, 9 Avenue du Pr Léon Bernard, 35000 Rennes (France)

    2017-06-15

    Estrogen receptors (ERs) α and β are distributed in most tissues of women and men. ERs are bound by estradiol (E2), a natural hormone, and mediate the pleiotropic and tissue-specific effects of E2, such as proliferation of breast epithelial cells or protection and differentiation of neuronal cells. Numerous environmental molecules, called endocrine disrupting compounds, also interact with ERs. Phytoestrogens belong to this large family and are considered potent therapeutic molecules that act through their selective estrogen receptor modulator (SERM) activity. Using breast cancer cell lines as a model of estrogen-dependent proliferation and a stably ER-expressing PC12 cell line as a model of neuronal differentiating cells, we studied the SERM activity of major dietary compounds, such as apigenin, liquiritigenin, daidzein, genistein, coumestrol, resveratrol and zearalenone. The ability of these compounds to induce ER-transactivation and breast cancer cell proliferation and enhance Nerve Growth Factor (NGF) -induced neuritogenesis was assessed. Surprisingly, although all compounds were able to activate the ER through an estrogen responsive element reporter gene, they showed differential activity toward proliferation or differentiation. Apigenin and resveratrol showed a partial or no proliferative effect on breast cancer cells but fully contributed to the neuritogenesis effect of NGF. However, daidzein and zearalenone showed full effects on cellular proliferation but did not induce cellular differentiation. In summary, our results suggest that the therapeutic potential of phytoestrogens can diverge depending on the molecule and the phenotype considered. Hence, apigenin and resveratrol might be used in the development of therapeutics for breast cancer and brain diseases. - Highlights: • SERM activity of dietary compounds on proliferation and differentiation is studied. • All the dietary compounds tested transactivate estrogen receptors. • Apigenin and

  4. Distinct roles of Rheb and Raptor in activating mTOR complex 1 for the self-renewal of hematopoietic stem cells.

    Science.gov (United States)

    Peng, Hui; Kasada, Atsuo; Ueno, Masaya; Hoshii, Takayuki; Tadokoro, Yuko; Nomura, Naho; Ito, Chiaki; Takase, Yusuke; Vu, Ha Thi; Kobayashi, Masahiko; Xiao, Bo; Worley, Paul F; Hirao, Atsushi

    2018-01-01

    The mammalian target of rapamycin (mTOR) complex 1 (mTORC1) senses a cell's energy status and environmental levels of nutrients and growth factors. In response, mTORC1 mediates signaling that controls protein translation and cellular metabolism. Although mTORC1 plays a critical role in hematopoiesis, it remains unclear which upstream stimuli regulate mTORC1 activity in the context of hematopoietic stem cells (HSC) maintenance in vivo. In this study, we investigated the function of Rheb, a critical regulator of mTORC1 activity controlled by the PI3K-AKT-TSC axis, both in HSC maintenance in mice at steady-state and in HSC-derived hematopoiesis post-transplantation. In contrast to the severe hematopoietic dysfunction caused by Raptor deletion, which completely inactivates mTORC1, Rheb deficiency in adult mice did not show remarkable hematopoietic failure. Lack of Rheb caused abnormalities in myeloid cells but did not have impact on hematopoietic regeneration in mice subjected to injury by irradiation. As previously reported, Rheb deficiency resulted in defective HSC-derived hematopoiesis post-transplantation. However, while Raptor is essential for HSC competitiveness in vivo, Rheb is dispensable for HSC maintenance under physiological conditions, indicating that the PI3K-AKT-TSC pathway does not contribute to mTORC1 activity for sustaining HSC self-renewal activity at steady-state. Thus, the various regulatory elements that impinge upstream of mTORC1 activation pathways are differentially required for HSC homeostasis in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. FT-IR spectra of the anti-HIV nucleoside analogue d4T (Stavudine). Solid state simulation by DFT methods and scaling by different procedures

    Science.gov (United States)

    Alcolea Palafox, M.; Kattan, D.; Afseth, N. K.

    2018-04-01

    A theoretical and experimental vibrational study of the anti-HIV d4T (stavudine or Zerit) nucleoside analogue was carried out. The predicted spectra in the three most stable conformers in the biological active anti-form of the isolated state were compared. Comparison of the conformers with those of the natural nucleoside thymidine was carried out. The calculated spectra were scaled by using different scaling procedures and three DFT methods. The TLSE procedure leads to the lowest error and is thus recommended for scaling. With the population of these conformers the IR gas-phase spectra were predicted. The crystal unit cell of the different polymorphism forms of d4T were simulated through dimer forms by using DFT methods. The scaled spectra of these dimer forms were compared. The FT-IR spectrum was recorded in the solid state in the 400-4000 cm-1 range. The respective vibrational bands were analyzed and assigned to different normal modes of vibration by comparison with the scaled vibrational values of the different dimer forms. Through this comparison, the polymorphous form of the solid state sample was identified. The study indicates that d4T exist only in the ketonic form in the solid state. The results obtained were in agreement with those determined in related anti-HIV nucleoside analogues.

  6. Dopamine D4 Receptor Counteracts Morphine-Induced Changes in µ Opioid Receptor Signaling in the Striosomes of the Rat Caudate Putamen

    Directory of Open Access Journals (Sweden)

    Diana Suárez-Boomgaard

    2014-01-01

    Full Text Available The mu opioid receptor (MOR is critical in mediating morphine analgesia. However, prolonged exposure to morphine induces adaptive changes in this receptor leading to the development of tolerance and addiction. In the present work we have studied whether the continuous administration of morphine induces changes in MOR protein levels, its pharmacological profile, and MOR-mediated G-protein activation in the striosomal compartment of the rat CPu, by using immunohistochemistry and receptor and DAMGO-stimulated [35S]GTPγS autoradiography. MOR immunoreactivity, agonist binding density and its coupling to G proteins are up-regulated in the striosomes by continuous morphine treatment in the absence of changes in enkephalin and dynorphin mRNA levels. In addition, co-treatment of morphine with the dopamine D4 receptor (D4R agonist PD168,077 fully counteracts these adaptive changes in MOR, in spite of the fact that continuous PD168,077 treatment increases the [3H]DAMGO Bmax values to the same degree as seen after continuous morphine treatment. Thus, in spite of the fact that both receptors can be coupled to Gi/0 protein, the present results give support for the existence of antagonistic functional D4R-MOR receptor-receptor interactions in the adaptive changes occurring in MOR of striosomes on continuous administration of morphine.

  7. A method for investigation of the D(4He, γ)6Li reaction in the Ultralow energy region under a high background

    Science.gov (United States)

    Bystritsky, V. M.; Dudkin, G. N.; Krylov, A. R.; Gazi, S.; Huran, J.; Nechaev, B. A.; Padalko, V. N.; Sadovsky, A. B.; Tuleushev, Yu. Zh.; Filipowicz, M.; Philippov, A. V.

    2016-07-01

    The cosmological lithium problem, that is, a noticeable discrepancy between the predicted and observed abundances of lithium, is in conflict with the Standard Big Bang Nucleosynthesis model. For example, the abundance of 7Li is 2-4 times smaller than predicted by the Standard Big Bang Nucleosynthesis. As to the abundance of 6Li, recent more accurate optical investigations have yielded only the upper limit on the 6Li/7Li ratio, which makes the problem of 6Li abundance and accordingly of disagreement with the Standard Big Bang Nucleosynthesis predictions less acute. However, experimental study of the D(4He, γ)6Li reaction cross section is still of current importance because there is a theoretical approach predicting its anomalously large value in the region of energies below the Standard Big Bang Nucleosynthesis energy. The work is dedicated to the measurement of the cross section for the D(4He, γ)6Li reaction proceeding in zirconium deuteride at the incident 4He+ion energy of 36 keV. The experiment is performed at a pulsed Hall plasma accelerator with an energy spread of 20% FWHM. A method for direct measurement of the background from the reaction chain D(4He, 4He)D→D(D, n)3He→(n, γ) and/or (n, n‧γ) ending with activation of the surrounding material by neutrons is proposed and implemented in the work. An upper limit on the D(4He, γ)6Li reaction cross section σ≤7·10-36 cm2 at the 90% confidence level is obtained.

  8. A method for investigation of the D("4He, γ)"6Li reaction in the Ultralow energy region under a high background

    International Nuclear Information System (INIS)

    Bystritsky, V.M.; Dudkin, G.N.; Krylov, A.R.; Gazi, S.; Huran, J.; Nechaev, B.A.; Padalko, V.N.; Sadovsky, A.B.; Tuleushev, Yu.Zh.; Filipowicz, M.; Philippov, A.V.

    2016-01-01

    The cosmological lithium problem, that is, a noticeable discrepancy between the predicted and observed abundances of lithium, is in conflict with the Standard Big Bang Nucleosynthesis model. For example, the abundance of "7Li is 2–4 times smaller than predicted by the Standard Big Bang Nucleosynthesis. As to the abundance of "6Li, recent more accurate optical investigations have yielded only the upper limit on the "6Li/"7Li ratio, which makes the problem of "6Li abundance and accordingly of disagreement with the Standard Big Bang Nucleosynthesis predictions less acute. However, experimental study of the D("4He, γ)"6Li reaction cross section is still of current importance because there is a theoretical approach predicting its anomalously large value in the region of energies below the Standard Big Bang Nucleosynthesis energy. The work is dedicated to the measurement of the cross section for the D("4He, γ)"6Li reaction proceeding in zirconium deuteride at the incident "4He"+ion energy of 36 keV. The experiment is performed at a pulsed Hall plasma accelerator with an energy spread of 20% FWHM. A method for direct measurement of the background from the reaction chain D("4He, "4He)D→D(D, n)"3He→(n, γ) and/or (n, n′γ) ending with activation of the surrounding material by neutrons is proposed and implemented in the work. An upper limit on the D("4He, γ)"6Li reaction cross section σ≤7·10"−"3"6 cm"2 at the 90% confidence level is obtained.

  9. Study on safety classifications of software used in nuclear power plants and distinct applications of verification and validation activities in each class

    International Nuclear Information System (INIS)

    Kim, B. R.; Oh, S. H.; Hwang, H. S.; Kim, D. I.

    2000-01-01

    This paper describes the safety classification regarding instrumentation and control (I and C) systems and their software used in nuclear power plants, provides regulatory positions for software important to safety, and proposes verification and validation (V and V) activities applied differently in software classes which are important elements in ensuring software quality assurance. In other word, the I and C systems important to safety are classified into IC-1, IC-2, IC-3, and Non-IC and their software are classified into safety-critical, safety-related, and non-safety software. Based upon these safety classifications, the extent of software V and V activities in each class is differentiated each other. In addition, the paper presents that the software for use in I and C systems important to safety is divided into newly-developed and previously-developed software in terms of design and implementation, and provides the regulatory positions on each type of software

  10. Second to fourth digit ratio (2D:4D and concentrations of circulating sex hormones in adulthood

    Directory of Open Access Journals (Sweden)

    Morris Howard A

    2011-04-01

    Full Text Available Abstract Background The second to fourth digit ratio (2D:4D is used as a marker of prenatal sex hormone exposure. The objective of this study was to examine whether circulating concentrations of sex hormones and SHBG measured in adulthood was associated with 2D:4D. Methods This analysis was based on a random sample from the Melbourne Collaborative Cohort Study. The sample consisted of of 1036 men and 620 post-menopausal women aged between 39 and 70 at the time of blood draw. Concentrations of circulating sex hormones were measured from plasma collected at baseline (1990-1994, while digit length was measured from hand photocopies taken during a recent follow-up (2003-2009. The outcome measures were circulating concentrations of testosterone, oestradiol, dehydroepiandrosterone sulphate, androstenedione, Sex Hormone Binding Globulin, androstenediol glucoronide for men only and oestrone sulphate for women only. Free testosterone and oestradiol were estimated using standard formulae derived empirically. Predicted geometric mean hormone concentrations (for tertiles of 2D:4D and conditional correlation coefficients (for continuous 2D:4D were obtained using mixed effects linear regression models. Results No strong associations were observed between 2D:4D measures and circulating concentrations of hormones for men or women. For males, right 2D:4D was weakly inversely associated with circulating testosterone (predicted geometric mean testosterone was 15.9 and 15.0 nmol/L for the lowest and highest tertiles of male right 2D:4D respectively (P-trend = 0.04. There was a similar weak association between male right 2D:4D and the ratio of testosterone to oestradiol. These associations were not evident in analyses of continuous 2D:4D. Conclusions There were no strong associations between any adult circulating concentration of sex hormone or SHGB and 2D:4D. These results contribute to the growing body of evidence indicating that 2D:4D is unrelated to adult sex

  11. Distinct Mechanism of Cysteine Oxidation-Dependent Activation and Cold Sensitization of Human Transient Receptor Potential Ankyrin 1 Channel by High and Low Oxaliplatin

    Directory of Open Access Journals (Sweden)

    Takahito Miyake

    2017-11-01

    Full Text Available Oxaliplatin, a third-generation platinum-based chemotherapeutic agent, displays unique acute peripheral neuropathy triggered or enhanced by cold, and accumulating evidence suggests that transient receptor potential ankyrin 1 (TRPA1 is responsible. TRPA1 is activated by oxaliplatin via a glutathione-sensitive mechanism. However, oxaliplatin interrupts hydroxylation of a proline residue located in the N-terminal region of TRPA1 via inhibition of prolyl hydroxylase (PHD, which causes sensitization of TRPA1 to reactive oxygen species (ROS. Furthermore, PHD inhibition endows cold-insensitive human TRPA1 (hTRPA1 with ROS-dependent cold sensitivity. Since cysteine oxidation and proline hydroxylation regulate its activity, their association with oxaliplatin-induced TRPA1 activation and acquirement of cold sensitivity were investigated in the present study. A high concentration of oxaliplatin (1 mM induced outward-rectifier whole-cell currents and increased the intracellular Ca2+ concentration in hTRPA1-expressing HEK293 cells, but did not increase the probability of hTRPA1 channel opening in the inside-out configuration. Oxaliplatin also induced the rapid generation of hydrogen peroxide, and the resultant Ca2+ influx was prevented in the presence of glutathione and in cysteine-mutated hTRPA1 (Cys641Ser-expressing cells, whereas proline-mutated hTRPA1 (Pro394Ala-expressing cells showed similar whole-cell currents and Ca2+ influx. By contrast, a lower concentration of oxaliplatin (100 μM did not increase the intracellular Ca2+ concentration but did confer cold sensitivity on hTRPA1-expressing cells, and this was inhibited by PHD2 co-overexpression. Cold sensitivity was abolished by the mitochondria-targeting ROS scavenger mitoTEMPO and was minimal in cysteine-mutated hTRPA1 (Cys641Ser or Cys665Ser-expressing cells. Thus, high oxaliplatin evokes ROS-mediated cysteine oxidation-dependent hTRPA1 activation independent of PHD activity, while a lower

  12. Microarray and pathway analysis reveal distinct mechanisms underlying cannabinoid-mediated modulation of LPS-induced activation of BV-2 microglial cells.

    Directory of Open Access Journals (Sweden)

    Ana Juknat

    Full Text Available Cannabinoids are known to exert immunosuppressive activities. However, the mechanisms which contribute to these effects are unknown. Using lipopolysaccharide (LPS to activate BV-2 microglial cells, we examined how Δ(9-tetrahydrocannabinol (THC, the major psychoactive component of marijuana, and cannabidiol (CBD the non-psychoactive component, modulate the inflammatory response. Microarray analysis of genome-wide mRNA levels was performed using Illumina platform and the resulting expression patterns analyzed using the Ingenuity Pathway Analysis to identify functional subsets of genes, and the Ingenuity System Database to denote the gene networks regulated by CBD and THC. From the 5338 transcripts that were differentially expressed across treatments, 400 transcripts were found to be upregulated by LPS, 502 by CBD+LPS and 424 by THC+LPS, while 145 were downregulated by LPS, 297 by CBD+LPS and 149 by THC+LPS, by 2-fold or more (p≤0.005. Results clearly link the effects of CBD and THC to inflammatory signaling pathways and identify new cannabinoid targets in the MAPK pathway (Dusp1, Dusp8, Dusp2, cell cycle related (Cdkn2b, Gadd45a as well as JAK/STAT regulatory molecules (Socs3, Cish, Stat1. The impact of CBD on LPS-stimulated gene expression was greater than that of THC. We attribute this difference to the fact that CBD highly upregulated several genes encoding negative regulators of both NFκB and AP-1 transcriptional activities, such as Trib3 and Dusp1 known to be modulated through Nrf2 activation. The CBD-specific expression profile reflected changes associated with oxidative stress and glutathione depletion via Trib3 and expression of ATF4 target genes. Furthermore, the CBD affected genes were shown to be controlled by nuclear factors usually involved in regulation of stress response and inflammation, mainly via Nrf2/Hmox1 axis and the Nrf2/ATF4-Trib3 pathway. These observations indicate that CBD, and less so THC, induce a cellular stress

  13. Energy transfer and reaction dynamics of matrix-isolated 1,2-difluoroethane-d4

    Science.gov (United States)

    Raff, Lionel M.

    1990-09-01

    The molecular dynamics of vibrationally excited 1,2-difluoroethane-d4 isolated in Ar, Kr, and Xe matrices at 12 K are investigated using trajectory methods. The matrix model is an fcc crystal containing 125 unit cells with 666 atoms in a cubic (5×5×5) arrangement. It is assumed that 1,2-difluoroethane-d4 is held interstitially within the volume bounded by the innermost unit cell of the crystal. The transport effects of the bulk are simulated using the velocity reset method introduced by Riley, Coltrin, and Diestler [J. Chem. Phys. 88, 5934 (1988)]. The system potential is written as the separable sum of a lattice potential, a lattice-molecule interaction and a gas-phase potential for 1,2-difluoroethane. The first two of these are assumed to have pairwise form while the molecular potential is a modified form of the global potential previously developed for 1,2-difluoroethane [J. Phys. Chem. 91, 3266 (1987)]. Calculated sublimation energies for the pure crystals are in good accord with the experimental data. The distribution of metastable-state energies for matrix-isolated 1,2-difluoroethane-d4 is Gaussian in form. In krypton, the full width at half maximum for the distribution is 0.37 eV. For a total excitation energy of 6.314 eV, the observed dynamic processes are vibrational relaxation, orientational exchange, and four-center DF elimination reactions. The first of these processes is characterized by a near linear, first-order decay curve with rate coefficients in the range 1.30-1.48×1011 s-1. The average rates in krypton and xenon are nearly equal. The process is slightly slower in argon. The decay curves exhibit characteristic high-frequency oscillations that are generally seen in energy transfer studies. It is demonstrated that these oscillations are associated with the frequencies for intramolecular energy transfer so that the entire frequency spectrum for such transfer processes can be obtained from the Fourier transform of the decay curve. Orientational

  14. Presence of D4 dopamine receptors in human prefrontal cortex: a postmortem study Presença de receptores dopaminérgicos D4 em córtex cerebral humano: um estudo post-mortem

    Directory of Open Access Journals (Sweden)

    Donatella Marazziti

    2007-06-01

    Full Text Available OBJECTIVE: The aim of our study was to explore the presence and the distribution of D4 dopamine receptors in postmortem human prefrontal cortex, by means of the binding of [³H]YM-09151-2, an antagonist that has equal affinity for D2, D3 and D4 receptors. It was therefore necessary to devise a unique assay method in order to distinguish and detect the D4 component. METHOD: Frontal cortex samples were harvested postmortem, during autopsy sessions, from 5 subjects. In the first assay, tissue homogenates were incubated with increasing concentrations of [³H]YM-09151-2, whereas L-745870, which has a high affinity for D4 and a low affinity for D2/D3 receptors, was used as the displacer. In the second assay, raclopride, which has a high affinity for D2/D3 receptors and a low affinity for D4 receptors, was used to block D2/D3. The L-745870 (500 nM was added to both assays in order to determine the nonspecific binding. RESULTS: Our experiments revealed the presence of specific and saturable binding of [³H]YM-09151-2. The blockade of D2 and D3 receptors with raclopride ensured that the D4 receptors were labeled. The mean maximum binding capacity was 88 ± 25 fmol/mg protein, and the dissociation constant was 0.8 ± 0.4 nM. DISCUSSION AND CONCLUSIONS: Our findings, although not conclusive, suggest that the density of D4 receptors is low in the human prefrontal cortex.OBJETIVO: O objetivo deste estudo foi quantificar a presença e a distribuição de receptores dopaminérgicos do tipo 4 (D4 no córtex cerebral humano em amostras post-mortem através do bloqueio com ³H-YM-09151-2 - um antagonista com afinidade equivalente pelos receptores D2, D3 e D4 - e do desenvolvimento de um método para a detecção específica do componente D4. MÉTODO: Foram obtidas amostras de córtex cerebral de cinco cadáveres. Em um primeiro ensaio, os homogeneizados de tecido cerebral foram incubados em concentrações crescentes de ³H-YM-09151-2, enquanto que o L-745

  15. Two distinct voltage-sensing domains control voltage sensitivity and kinetics of current activation in CaV1.1 calcium channels.

    Science.gov (United States)

    Tuluc, Petronel; Benedetti, Bruno; Coste de Bagneaux, Pierre; Grabner, Manfred; Flucher, Bernhard E

    2016-06-01

    Alternative splicing of the skeletal muscle CaV1.1 voltage-gated calcium channel gives rise to two channel variants with very different gating properties. The currents of both channels activate slowly; however, insertion of exon 29 in the adult splice variant CaV1.1a causes an ∼30-mV right shift in the voltage dependence of activation. Existing evidence suggests that the S3-S4 linker in repeat IV (containing exon 29) regulates voltage sensitivity in this voltage-sensing domain (VSD) by modulating interactions between the adjacent transmembrane segments IVS3 and IVS4. However, activation kinetics are thought to be determined by corresponding structures in repeat I. Here, we use patch-clamp analysis of dysgenic (CaV1.1 null) myotubes reconstituted with CaV1.1 mutants and chimeras to identify the specific roles of these regions in regulating channel gating properties. Using site-directed mutagenesis, we demonstrate that the structure and/or hydrophobicity of the IVS3-S4 linker is critical for regulating voltage sensitivity in the IV VSD, but by itself cannot modulate voltage sensitivity in the I VSD. Swapping sequence domains between the I and the IV VSDs reveals that IVS4 plus the IVS3-S4 linker is sufficient to confer CaV1.1a-like voltage dependence to the I VSD and that the IS3-S4 linker plus IS4 is sufficient to transfer CaV1.1e-like voltage dependence to the IV VSD. Any mismatch of transmembrane helices S3 and S4 from the I and IV VSDs causes a right shift of voltage sensitivity, indicating that regulation of voltage sensitivity by the IVS3-S4 linker requires specific interaction of IVS4 with its corresponding IVS3 segment. In contrast, slow current kinetics are perturbed by any heterologous sequences inserted into the I VSD and cannot be transferred by moving VSD I sequences to VSD IV. Thus, CaV1.1 calcium channels are organized in a modular manner, and control of voltage sensitivity and activation kinetics is accomplished by specific molecular mechanisms

  16. Coordination polymers of Fe(iii) and Al(iii) ions with TCA ligand: distinctive fluorescence, CO2 uptake, redox-activity and oxygen evolution reaction.

    Science.gov (United States)

    Dhara, Barun; Sappati, Subrahmanyam; Singh, Santosh K; Kurungot, Sreekumar; Ghosh, Prasenjit; Ballav, Nirmalya

    2016-04-28

    Fe and Al belong to different groups in the periodic table, one from the p-block and the other from the d-block. In spite of their different groups, they have the similarity of exhibiting a stable 3+ oxidation state. Here we have prepared Fe(iii) and Al(iii) based coordination polymers in the form of metal-organic gels with the 4,4',4''-tricarboxyltriphenylamine (TCA) ligand, namely Fe-TCA and Al-TCA, and evaluated some important physicochemical properties. Specifically, the electrical conductivity, redox-activity, porosity, and electrocatalytic activity (oxygen evolution reaction) of the Fe-TCA system were noted to be remarkably higher than those of the Al-TCA system. As for the photophysical properties, almost complete quenching of the fluorescence originating from TCA was observed in case of the Fe-TCA system, whereas for the Al-TCA system a significant retention of fluorescence with red-shifted emission was observed. Quantum mechanical calculations based on density functional theory (DFT) were performed to unravel the origin of such discriminative behaviour of these coordination polymer systems.

  17. Bio-based synthesis of silver nanoparticles from orange waste: effects of distinct biomolecule coatings on size, morphology, and antimicrobial activity.

    Science.gov (United States)

    de Barros, Caio Henrique Nasi; Cruz, Guilherme Crispim Faria; Mayrink, Willian; Tasic, Ljubica

    2018-01-01

    Despite the numerous reports on biological syntheses of silver nanoparticles (AgNPs), little is known about the composition of their capping agents, protein corona of plant extract-mediated synthesis, and their influence on the properties of AgNPs. Here, orange ( Citrus sinensis ) waste was utilized as a source of an extract for AgNP synthesis (the protein corona composition of which was elucidated), and also as a starting material for hesperidin and nanocellulose extraction, which were used for bio-based AgNP synthesis. A comparison of the results using the two methods of synthesis is presented. AgNPs were synthesized using orange ( C. sinensis ) peel extract (Or-AgNPs) in a biological route, and using hesperidin (Hsd-AgNPs) and nanocellulose (extracted from oranges) in a green chemical route. Characterization of nanoparticles was carried out using zeta potential and hydrodynamic size measurements, transmission electron microscopy, and X-ray diffraction. Elucidation of proteins from protein corona was performed via ultra performance liquid chromatography-tandem mass spectrometer experiments. Antimicrobial activity was assessed via minimum inhibitory concentration assays against Xanthomonas axonopodis pv. citri ( Xac ), the bacterium that causes citric canker in oranges. Or-AgNPs were not completely uniform in morphology, having a size of 48.1±20.5 nm and a zeta potential of -19.0±0.4 mV. Stabilization was performed mainly by three proteins, which were identified by tandem mass spectrometry (MS/MS) experiments. Hsd-AgNPs were smaller (25.4±12.5 nm) and had uniform morphology. Nanocellulose provided a strong steric and electrostatic (-28.2±1.0 mV) stabilization to the nanoparticles. Both AgNPs presented roughly the same activity against Xac , with the minimum inhibitory concentration range between 22 and 24 μg mL -1 . Despite the fact that different capping biomolecules on AgNPs had an influence on morphology, size, and stability of AgNPs, the antibacterial

  18. Bio-based synthesis of silver nanoparticles from orange waste: effects of distinct biomolecule coatings on size, morphology, and antimicrobial activity

    Science.gov (United States)

    de Barros, Caio Henrique Nasi; Cruz, Guilherme Crispim Faria; Mayrink, Willian; Tasic, Ljubica

    2018-01-01

    Purpose Despite the numerous reports on biological syntheses of silver nanoparticles (AgNPs), little is known about the composition of their capping agents, protein corona of plant extract-mediated synthesis, and their influence on the properties of AgNPs. Here, orange (Citrus sinensis) waste was utilized as a source of an extract for AgNP synthesis (the protein corona composition of which was elucidated), and also as a starting material for hesperidin and nanocellulose extraction, which were used for bio-based AgNP synthesis. A comparison of the results using the two methods of synthesis is presented. Methods AgNPs were synthesized using orange (C. sinensis) peel extract (Or-AgNPs) in a biological route, and using hesperidin (Hsd-AgNPs) and nanocellulose (extracted from oranges) in a green chemical route. Characterization of nanoparticles was carried out using zeta potential and hydrodynamic size measurements, transmission electron microscopy, and X-ray diffraction. Elucidation of proteins from protein corona was performed via ultra performance liquid chromatography-tandem mass spectrometer experiments. Antimicrobial activity was assessed via minimum inhibitory concentration assays against Xanthomonas axonopodis pv. citri (Xac), the bacterium that causes citric canker in oranges. Results Or-AgNPs were not completely uniform in morphology, having a size of 48.1±20.5 nm and a zeta potential of −19.0±0.4 mV. Stabilization was performed mainly by three proteins, which were identified by tandem mass spectrometry (MS/MS) experiments. Hsd-AgNPs were smaller (25.4±12.5 nm) and had uniform morphology. Nanocellulose provided a strong steric and electrostatic (−28.2±1.0 mV) stabilization to the nanoparticles. Both AgNPs presented roughly the same activity against Xac, with the minimum inhibitory concentration range between 22 and 24 μg mL−1. Conclusion Despite the fact that different capping biomolecules on AgNPs had an influence on morphology, size, and stability

  19. Bio-based synthesis of silver nanoparticles from orange waste: effects of distinct biomolecule coatings on size, morphology, and antimicrobial activity

    Directory of Open Access Journals (Sweden)

    Barros CHN

    2018-03-01

    Full Text Available Caio Henrique Nasi de Barros, Guilherme Crispim Faria Cruz, Willian Mayrink, Ljubica Tasic Laboratory of Chemical Biology, Department of Organic Chemistry, Instituto de Química da Universidade Estadual de Campinas–Unicamp, Campinas, SP, Brazil Purpose: Despite the numerous reports on biological syntheses of silver nanoparticles (AgNPs, little is known about the composition of their capping agents, protein corona of plant extract-mediated synthesis, and their influence on the properties of AgNPs. Here, orange (Citrus sinensis waste was utilized as a source of an extract for AgNP synthesis (the protein corona composition of which was elucidated, and also as a starting material for hesperidin and nanocellulose extraction, which were used for bio-based AgNP synthesis. A comparison of the results using the two methods of synthesis is presented. Methods: AgNPs were synthesized using orange (C. sinensis peel extract (­Or-AgNPs in a biological route, and using hesperidin (Hsd-AgNPs and nanocellulose (extracted from oranges in a green chemical route. Characterization of nanoparticles was carried out using zeta potential and hydrodynamic size measurements, transmission electron microscopy, and X-ray diffraction. Elucidation of proteins from protein corona was performed via ultra performance liquid chromatography-tandem mass spectrometer experiments. Antimicrobial activity was assessed via minimum inhibitory concentration assays against Xanthomonas axonopodis pv. citri (Xac, the bacterium that causes citric canker in oranges. Results: Or-AgNPs were not completely uniform in morphology, having a size of 48.1±20.5 nm and a zeta potential of −19.0±0.4 mV. Stabilization was performed mainly by three proteins, which were identified by tandem mass spectrometry (MS/MS experiments. Hsd-AgNPs were smaller (25.4±12.5 nm and had uniform morphology. Nanocellulose provided a strong steric and electrostatic (−28.2±1.0 mV stabilization to the nanoparticles

  20. Associations between dopamine D4 receptor gene variation with both infidelity and sexual promiscuity.

    Science.gov (United States)

    Garcia, Justin R; MacKillop, James; Aller, Edward L; Merriwether, Ann M; Wilson, David Sloan; Lum, J Koji

    2010-11-30

    Human sexual behavior is highly variable both within and between populations. While sex-related characteristics and sexual behavior are central to evolutionary theory (sexual selection), little is known about the genetic bases of individual variation in sexual behavior. The variable number tandem repeats (VNTR) polymorphism in exon III of the human dopamine D4 receptor gene (DRD4) has been correlated with an array of behavioral phenotypes and may be predicatively responsible for variation in motivating some sexual behaviors, particularly promiscuity and infidelity. We administered an anonymous survey on personal history of sexual behavior and intimate relationships to 181 young adults. We also collected buccal wash samples and genotyped the DRD4 VNTR. Here we show that individuals with at least one 7-repeat allele (7R+) report a greater categorical rate of promiscuous sexual behavior (i.e., having ever had a "one-night stand") and report a more than 50% increase in instances of sexual infidelity. DRD4 VNTR genotype varies considerably within and among populations and has been subject to relatively recent, local selective pressures. Individual differences in sexual behavior are likely partially mediated by individual genetic variation in genes coding for motivation and reward in the brain. Conceptualizing these findings in terms of r/K selection theory suggests a mechanism for selective pressure for and against the 7R+ genotype that may explain the considerable global allelic variation for this polymorphism.

  1. Classical and quantum aspects of BPS black holes in N=2,D=4 heterotic string compactifications

    International Nuclear Information System (INIS)

    Rey, S.-J.

    1997-01-01

    We study classical and quantum aspects of D=4, N=2 BPS black holes for T 2 compactification of D=6, N=1 heterotic string vacua. We extend dynamical relaxation phenomena of moduli fields to a background consisting of a BPS soliton or a black hole and provide a simpler but more general derivation of the Ferrara-Kallosh extremized black hole mass and entropy. We study quantum effects to the BPS black hole mass spectra and to their dynamical relaxation. We show that, despite non-renormalizability of string effective supergravity, the quantum effect modifies BPS mass spectra only through coupling constant and moduli field renormalizations. Based on target-space duality, we establish a perturbative non-renormalization theorem and obtain the exact BPS black hole mass and entropy in terms of the renormalized string loop-counting parameter and renormalized moduli fields. We show that a similar conclusion holds, in the large T 2 limit, for leading non-perturbative correction. We finally discuss implications to type-I and type-IIA Calabi-Yau black holes. (orig.)

  2. Domain 4 (D4 of Perfringolysin O to Visualize Cholesterol in Cellular Membranes—The Update

    Directory of Open Access Journals (Sweden)

    Masashi Maekawa

    2017-03-01

    Full Text Available The cellular membrane of eukaryotes consists of phospholipids, sphingolipids, cholesterol and membrane proteins. Among them, cholesterol is crucial for various cellular events (e.g., signaling, viral/bacterial infection, and membrane trafficking in addition to its essential role as an ingredient of steroid hormones, vitamin D, and bile acids. From a micro-perspective, at the plasma membrane, recent emerging evidence strongly suggests the existence of lipid nanodomains formed with cholesterol and phospholipids (e.g., sphingomyelin, phosphatidylserine. Thus, it is important to elucidate how cholesterol behaves in membranes and how the behavior of cholesterol is regulated at the molecular level. To elucidate the complexed characteristics of cholesterol in cellular membranes, a couple of useful biosensors that enable us to visualize cholesterol in cellular membranes have been recently developed by utilizing domain 4 (D4 of Perfringolysin O (PFO, theta toxin, a cholesterol-binding toxin. This review highlights the current progress on development of novel cholesterol biosensors that uncover new insights of cholesterol in cellular membranes.

  3. Associations between Dopamine D4 Receptor Gene Variation with Both Infidelity and Sexual Promiscuity

    Science.gov (United States)

    Garcia, Justin R.; MacKillop, James; Aller, Edward L.; Merriwether, Ann M.; Wilson, David Sloan; Lum, J. Koji

    2010-01-01

    Background Human sexual behavior is highly variable both within and between populations. While sex-related characteristics and sexual behavior are central to evolutionary theory (sexual selection), little is known about the genetic bases of individual variation in sexual behavior. The variable number tandem repeats (VNTR) polymorphism in exon III of the human dopamine D4 receptor gene (DRD4) has been correlated with an array of behavioral phenotypes and may be predicatively responsible for variation in motivating some sexual behaviors, particularly promiscuity and infidelity. Methodology/Principal Findings We administered an anonymous survey on personal history of sexual behavior and intimate relationships to 181 young adults. We also collected buccal wash samples and genotyped the DRD4 VNTR. Here we show that individuals with at least one 7-repeat allele (7R+) report a greater categorical rate of promiscuous sexual behavior (i.e., having ever had a “one-night stand”) and report a more than 50% increase in instances of sexual infidelity. Conclusions/Significance DRD4 VNTR genotype varies considerably within and among populations and has been subject to relatively recent, local selective pressures. Individual differences in sexual behavior are likely partially mediated by individual genetic variation in genes coding for motivation and reward in the brain. Conceptualizing these findings in terms of r/K selection theory suggests a mechanism for selective pressure for and against the 7R+ genotype that may explain the considerable global allelic variation for this polymorphism. PMID:21152404

  4. Associations between dopamine D4 receptor gene variation with both infidelity and sexual promiscuity.

    Directory of Open Access Journals (Sweden)

    Justin R Garcia

    2010-11-01

    Full Text Available Human sexual behavior is highly variable both within and between populations. While sex-related characteristics and sexual behavior are central to evolutionary theory (sexual selection, little is known about the genetic bases of individual variation in sexual behavior. The variable number tandem repeats (VNTR polymorphism in exon III of the human dopamine D4 receptor gene (DRD4 has been correlated with an array of behavioral phenotypes and may be predicatively responsible for variation in motivating some sexual behaviors, particularly promiscuity and infidelity.We administered an anonymous survey on personal history of sexual behavior and intimate relationships to 181 young adults. We also collected buccal wash samples and genotyped the DRD4 VNTR. Here we show that individuals with at least one 7-repeat allele (7R+ report a greater categorical rate of promiscuous sexual behavior (i.e., having ever had a "one-night stand" and report a more than 50% increase in instances of sexual infidelity.DRD4 VNTR genotype varies considerably within and among populations and has been subject to relatively recent, local selective pressures. Individual differences in sexual behavior are likely partially mediated by individual genetic variation in genes coding for motivation and reward in the brain. Conceptualizing these findings in terms of r/K selection theory suggests a mechanism for selective pressure for and against the 7R+ genotype that may explain the considerable global allelic variation for this polymorphism.

  5. Domain 4 (D4) of Perfringolysin O to Visualize Cholesterol in Cellular Membranes-The Update.

    Science.gov (United States)

    Maekawa, Masashi

    2017-03-03

    The cellular membrane of eukaryotes consists of phospholipids, sphingolipids, cholesterol and membrane proteins. Among them, cholesterol is crucial for various cellular events (e.g., signaling, viral/bacterial infection, and membrane trafficking) in addition to its essential role as an ingredient of steroid hormones, vitamin D, and bile acids. From a micro-perspective, at the plasma membrane, recent emerging evidence strongly suggests the existence of lipid nanodomains formed with cholesterol and phospholipids (e.g., sphingomyelin, phosphatidylserine). Thus, it is important to elucidate how cholesterol behaves in membranes and how the behavior of cholesterol is regulated at the molecular level. To elucidate the complexed characteristics of cholesterol in cellular membranes, a couple of useful biosensors that enable us to visualize cholesterol in cellular membranes have been recently developed by utilizing domain 4 (D4) of Perfringolysin O (PFO, theta toxin), a cholesterol-binding toxin. This review highlights the current progress on development of novel cholesterol biosensors that uncover new insights of cholesterol in cellular membranes.

  6. Fluoride Bridges as Structure-Directing Motifs in 3d-4f Cluster Chemistry

    DEFF Research Database (Denmark)

    Birk, Torben; Pedersen, Kasper; Thuesen, Christian Aa.

    2012-01-01

    The use of kinetically robust chromium(III) fluorido complexes as synthons for mixed 3d-4f clusters is reported. The tendency toward linear {CrIII–F–LnIII} units dictates the cluster topology. Specifically, we show that reaction of cis-[CrIIIF2(NN)2]NO3 (NN = 1,10-phenanthroline (“phen”) or 2......-nuclear complex and fac-[CrIIIF3L′], with L′ = 1,1,1-tris-((methylamino)methylethane) (“Me3tame”), reacts with [Ln(hfac)3(H2O)2] (hfacH = 1,1,1,5,5,5-hexafluoroacetylacetone) to yield an isostructural series of {Ln3Cr2} (10–14) trigonal bipyramids with no central ligand. The formation of the latter is accompanied...... by a partial solvolysis of the Cr(III) precursor but without formation of insoluble LnF3. The magnetic properties of the gadolinium containing clusters allow quantification of fluoride-mediated, antiferromagnetic Gd–Cr exchange interactions of magnitude between 0.14 cm–1 and 0.71 cm–1 (Ĥ = J12Ŝ1·Ŝ2...

  7. The distinction between chondroma and chondrosarcoma using chemical element mass fractions in tumors determined by neutron activation analysis as diagnostic markers

    International Nuclear Information System (INIS)

    Zaichick, Vladimir; Zaichick, Sofia

    2016-01-01

    The Ca, Cl, Mg, Na, and P content and Ca/P, Ca/Mg, Ca/Na, Cl/Ca, and Cl/Na ratios in tissue of intact bone, chondroma and chondrosarcoma were investigated by neutron activation analysis. It was shown that higher mass fraction of Cl and Na and also Cl/Na mass fraction ratio as well as lower Ca/Cl and Ca/Na mass fraction ratios are typical of the chondrosarcoma tissue compared to chondroma. Finally, it was proposed to use the estimation of such parameters as the Cl mass fraction and the Ca/Cl and Ca/Na mass fraction ratios as an additional test for differential diagnosis between chondroma and chondrosarcoma. (author)

  8. Distinct neuronal activation patterns are associated with PCP-induced social withdrawal and its reversal by the endocannabinoid-enhancing drug URB597.

    Science.gov (United States)

    Matricon, Julien; Seillier, Alexandre; Giuffrida, Andrea

    2016-09-01

    The fatty acid amide hydrolase inhibitor, URB597, an endocannabinoid enhancing drug, reverses social withdrawal in the sub-chronic PCP rat model of schizophrenia, but reduces social interaction (SI) in controls. To identify the anatomical substrates associated with PCP-induced social withdrawal and the contrasting effects of URB597 on SI in PCP- versus saline-treated rats, we analyzed SI-induced c-Fos expression in 28 brain areas relevant to schizophrenia and/or social behavior following vehicle or URB597 administration. In saline-treated rats, SI was accompanied by changes in c-Fos expression in the infralimbic and orbitofrontal cortices, dorsomedial caudate putamen, ventrolateral nucleus of the septum, dorsolateral periaqueductal gray (dlPAG) and central amygdala. Except for the dlPAG, these changes were not observed in PCP-treated rats or in saline-treated rats receiving URB597. In the dorsomedial part of the bed nucleus of the stria terminalis (dmBNST), SI-induced c-Fos expression was observed only in PCP-treated rats. Interestingly, URB597 in PCP-treated rats restored a similar c-Fos expression pattern as observed in saline-treated rats: activation of the orbitofrontal cortex, inhibition of the central amygdala and suppression of activation of the dmBNST. These data suggest that orbitofrontal cortex, central amygdala and dmBNST play a critical role in the reversal of PCP-induced social withdrawal by URB597. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  9. Airway epithelial cell exposure to distinct e-cigarette liquid flavorings reveals toxicity thresholds and activation of CFTR by the chocolate flavoring 2,5-dimethypyrazine.

    Science.gov (United States)

    Sherwood, Cara L; Boitano, Scott

    2016-05-17

    that the increases in ion conductance evoked by 2,5-dimethylpyrazine were largely attributed to a protein kinase A-dependent (PKA) activation of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel. Data from our high-capacity screening assays demonstrates that individual e-cigarette liquid flavoring chemicals vary in their cytotoxicity profiles and that some constituents evoke a cellular physiological response on their own independent of cell death. The activation of CFTR by 2,5-dimethylpyrazine may have detrimental consequences for airway surface liquid homeostasis in individuals that use e-cigarettes habitually.

  10. Transcription, Signaling Receptor Activity, Oxidative Phosphorylation, and Fatty Acid Metabolism Mediate the Presence of Closely Related Species in Distinct Intertidal and Cold-Seep Habitats.

    Science.gov (United States)

    Van Campenhout, Jelle; Vanreusel, Ann; Van Belleghem, Steven; Derycke, Sofie

    2015-12-03

    Bathyal cold seeps are isolated extreme deep-sea environments characterized by low species diversity while biomass can be high. The Håkon Mosby mud volcano (Barents Sea, 1,280 m) is a rather stable chemosynthetic driven habitat characterized by prominent surface bacterial mats with high sulfide concentrations and low oxygen levels. Here, the nematode Halomonhystera hermesi thrives in high abundances (11,000 individuals 10 cm(-2)). Halomonhystera hermesi is a member of the intertidal Halomonhystera disjuncta species complex that includes five cryptic species (GD1-5). GD1-5's common habitat is characterized by strong environmental fluctuations. Here, we compared the transcriptomes of H. hermesi and GD1, H. hermesi's closest relative. Genes encoding proteins involved in oxidative phosphorylation are more strongly expressed in H. hermesi than in GD1, and many genes were only observed in H. hermesi while being completely absent in GD1. Both observations could in part be attributed to high sulfide concentrations and low oxygen levels. Additionally, fatty acid elongation was also prominent in H. hermesi confirming the importance of highly unsaturated fatty acids in this species. Significant higher amounts of transcription factors and genes involved in signaling receptor activity were observed in GD1 (many of which were completely absent in H. hermesi), allowing fast signaling and transcriptional reprogramming which can mediate survival in dynamic intertidal environments. GC content was approximately 8% higher in H. hermesi coding unigenes resulting in differential codon usage between both species and a higher proportion of amino acids with GC-rich codons in H. hermesi. In general our results showed that most pathways were active in both environments and that only three genes are under natural selection. This indicates that also plasticity should be taken in consideration in the evolutionary history of Halomonhystera species. Such plasticity, as well as possible

  11. Validation of digit-length ratio (2D:4D) assessments on the basis of DXA-derived hand scans

    International Nuclear Information System (INIS)

    Romann, Michael; Fuchslocher, Jörg

    2015-01-01

    The second-to-fourth digit-length ratio (2D:4D) may be a correlate of prenatal sex steroids, and it has been linked to sporting prowess. The aim of the study was to validate dual-energy X-ray-absorptiometry (DXA) as a technique to assess 2D:4D in soccer players under 15 years of age (U-15). Paired X-ray and DXA scans of the left hands of 63 male U-15 elite soccer players (age: 14.0 ± 0.3 years) were performed, and 2D:4D was then compared between the two techniques. The 2D:4D measurements were performed twice by two blinded raters. Intrarater and interrater reliability, as well as agreement between the X-ray and the DXA assessments, were tested. Intrarater reliabilities of both raters using X-ray with intraclass correlation coefficients (ICCs) of 0.97 and 0.90 were excellent. Using DXA, the ICCs were 0.90 and 0.91 thus also showing excellent reliability. Interrater reliabilities were excellent using both the X-ray (ICC of 0.94) and the DXA (ICC of 0.90), assessments respectively. Bland-Altman plots demonstrated that the 2D:4D ratios of the two raters did not differ significantly between the X-ray and the DXA assessments. The standard errors of estimate were 0.01 for both techniques. The 95% limits of agreement of ±0.018 (±2.0%) and ±0.023 (±2.6%), respectively, were within the acceptable tolerance of 5%, and showed very good agreement. DXA offered a replicable technique for assessing 2D:4D in youth soccer players. Therefore, the DXA technique seems to be an alternative method for evaluating 2D:4D in youth sports

  12. Geochemical characterization of two distinctive systems with evidence of chemosynthetic activity, explored at the SE Pacific margin off Chile (46°S and 33°S)

    Science.gov (United States)

    Muñoz, Práxedes; Cárdenas, Lissette J.; Garbe-Schönberg, Dieter; Sellanes, Javier; Dezileau, Laurent; Melville, Ives; Mendes, Stephanie D.

    2016-11-01

    This study presents the geochemical composition of superficial sediment under oxic and suboxic bottom water conditions along the Chilean continental margin (SE Pacific), where evidence for benthic chemosynthetic activity associated with diffuse seeping of chemically reduced fluids has been reported. The exploration was carried out at: (1) the Chilean Triple Junction (CTJ), at a water depth of ∼2900 m, with the additional indication of hydrothermal activity near a methane-rich cold-seep area (46°S) (German et al., 2010); and (2) the El Quisco methane seep site (EQSS), at ∼340 m water depth (33°S) (Melo et al., 2007; Krylova et al., 2014). While the deeper CTJ is located within an oxic environment (dissolved oxygen in the bottom waters: 164 μM), the shallower EQSS lies within a suboxic environment (dissolved oxygen in bottom water: 23 μM), located within the lower limit of the SE Pacific oxygen minimum zone (OMZ). Pore water from short cores was analyzed for dissolved major, minor, and trace elements (Cl, Na, Mg, K, Ca, Sr, Si, B, P, Ba, Pb, Mn, Fe, Cd, U, and Mo), δ13DIC, sulfide, sulfate, and methane. The solid sediment fraction was likewise analyzed for total organic carbon (TOC), metals, and redox potential. Elevated sediment temperatures were found in superficial sediments (5-13 °C) at the CTJ site, which could be due to warm fluids associated with the proximity of the ridge, where hydrothermal vents may occur. Reduced fluids were also present here, indicated by higher Mn fluxes toward the water column even in oxidized sediments (RPD > 8 cm), which contrasted with the lower fluxes in reduced sediments of the EQSS site (RPD ∼ 2 cm). 13C-depleted DIC, anomalously low pore water Cl (∼15 ppb), and low concentrations of other major elements may be the result of dilution by fluid seeping and precipitation of major elements, producing authigenic enrichment (Ca, Mg, Sr). The fluid could also: (a) be diluted by pure water produced during methane hydrate

  13. Dopamine D4 Receptor Polymorphism and Sex Interact to Predict Children's Affective Knowledge

    Directory of Open Access Journals (Sweden)

    Sharon eBen-Israel

    2015-06-01

    Full Text Available Affective knowledge, the ability to understand others’ emotional states, is considered to be a fundamental part in efficient social interaction. Affective knowledge can be seen as related to cognitive empathy, and in the framework of Theory of Mind (ToM as affective ToM. Previous studies found that cognitive empathy and ToM are heritable, yet little is known regarding the specific genes involved in individual variability in affective knowledge. Investigating the genetic basis of affective knowledge is important for understanding brain mechanisms underlying socio-cognitive abilities. The 7-repeat (7R allele within the third exon of the Dopamine D4 receptor gene (DRD4-III has been a focus of interest, due to accumulated knowledge regarding its relevance to individual differences in prosocial behavior. A recent study suggests that an interaction between the DRD4-III polymorphism and sex is associated with cognitive empathy among adults. We aimed to examine the same association in two childhood age groups. Children (N = 280, age 3.5 years, N = 283, age 5 years participated as part of the Longitudinal Israel Study of Twins (LIST. Affective knowledge was assessed through children’s responses to an illustrated story describing different emotional situations, told in a laboratory setting. The findings suggest a significant interaction between sex and the DRD4-III polymorphism, replicated in both age groups. Boy carriers of the 7R allele had higher affective knowledge scores than girls, whereas in the absence of the 7R there was no significant sex effect on affective knowledge. The results support the importance of DRD4-III polymorphism and sex differences to social development. Possible explanations for differences from adult findings are discussed, as are pathways for future studies.

  14. Mitochondrial DNA haplogroup D4a is a marker for extreme longevity in Japan.

    Directory of Open Access Journals (Sweden)

    Erhan Bilal

    Full Text Available We report results from the analysis of complete mitochondrial DNA (mtDNA sequences from 112 Japanese semi-supercentenarians (aged above 105 years combined with previously published data from 96 patients in each of three non-disease phenotypes: centenarians (99-105 years of age, healthy non-obese males, obese young males and four disease phenotypes, diabetics with and without angiopathy, and Alzheimer's and Parkinson's disease patients. We analyze the correlation between mitochondrial polymorphisms and the longevity phenotype using two different methods. We first use an exhaustive algorithm to identify all maximal patterns of polymorphisms shared by at least five individuals and define a significance score for enrichment of the patterns in each phenotype relative to healthy normals. Our study confirms the correlations observed in a previous study showing enrichment of a hierarchy of haplogroups in the D clade for longevity. For the extreme longevity phenotype we see a single statistically significant signal: a progressive enrichment of certain "beneficial" patterns in centenarians and semi-supercentenarians in the D4a haplogroup. We then use Principal Component Spectral Analysis of the SNP-SNP Covariance Matrix to compare the measured eigenvalues to a Null distribution of eigenvalues on Gaussian datasets to determine whether the correlations in the data (due to longevity arises from some property of the mutations themselves or whether they are due to population structure. The conclusion is that the correlations are entirely due to population structure (phylogenetic tree. We find no signal for a functional mtDNA SNP correlated with longevity. The fact that the correlations are from the population structure suggests that hitch-hiking on autosomal events is a possible explanation for the observed correlations.

  15. Lack of association between digit ratio (2D:4D) and assertiveness: replication in a large sample.

    Science.gov (United States)

    Voracek, Martin

    2009-12-01

    Findings regarding within-sex associations of digit ratio (2D:4D), a putative pointer to long-lasting effects of prenatal androgen action, and sexually differentiated personality traits have generally been inconsistent or unreplicable, suggesting that effects in this domain, if any, are likely small. In contrast to evidence from Wilson's important 1983 study, a forerunner of modern 2D:4D research, two recent studies in 2005 and 2008 by Freeman, et al. and Hampson, et al. showed assertiveness, a presumably male-typed personality trait, was not associated with 2D:4D; however, these studies were clearly statistically underpowered. Hence this study examined this question anew, based on a large sample of 491 men and 627 women. Assertiveness was only modestly sexually differentiated, favoring men, and a positive correlate of age and education and a negative correlate of weight and Body Mass Index among women, but not men. Replicating the two prior studies, 2D:4D was throughout unrelated to assertiveness scores. This null finding was preserved with controls for correlates of assertiveness, also in nonparametric analysis and with tests for curvilinear relations. Discussed are implications of this specific null finding, now replicated in a large sample, for studies of 2D:4D and personality in general and novel research approaches to proceed in this field.

  16. Stem/Progenitor Cell Proteoglycans Decorated with 7-D-4, 4-C-3 and 3-B-3(-) Chondroitin Sulphate Motifs Are Morphogenetic Markers Of Tissue Development.

    Science.gov (United States)

    Hayes, Anthony J; Smith, Susan M; Caterson, Bruce; Melrose, James

    2018-06-11

    This study reviewed the occurrence of chondroitin sulphate (CS) motifs 4-C-3, 7-D-4 and 3-B-3(-) which are expressed by progenitor cells in tissues undergoing morphogenesis. These motifs have a transient early expression pattern during tissue development and also appear in mature tissues during pathological remodeling and attempted repair processes by activated adult stem cells. The CS motifs are information and recognition modules, which may regulate cellular behavior and delineate stem cell niches in developmental tissues. One of the difficulties in determining the precise role of stem cells in tissue development and repair processes is their short engraftment period and the lack of specific markers, which differentiate the activated stem cell lineages from the resident cells. The CS sulphation motifs 7-D-4, 4-C-3 and 3-B-3 (-) decorate cell surface proteoglycans on activated stem/progenitor cells and appear to identify these cells in transitional areas of tissue development and in tissue repair and may be applicable to determining a more precise role for stem cells in tissue morphogenesis. This article is protected by copyright. All rights reserved. © 2018 AlphaMed Press.

  17. n-Alkane and clofibrate, a peroxisome proliferator, activate transcription of ALK2 gene encoding cytochrome P450alk2 through distinct cis-acting promoter elements in Candida maltosa

    International Nuclear Information System (INIS)

    Kogure, Takahisa; Takagi, Masamichi; Ohta, Akinori

    2005-01-01

    The ALK2 gene, encoding one of the n-alkane-hydroxylating cytochromes P450 in Candida maltosa, is induced by n-alkanes and a peroxisome proliferator, clofibrate. Deletion analysis of this gene's promoter revealed two cis-acting elements-an n-alkane-responsive element (ARE2) and a clofibrate-responsive element (CRE2)-that partly overlap in sequence but have distinct functions. ARE2-mediated activation responded to n-alkanes but not to clofibrate and was repressed by glucose. CRE2-mediated activation responded to polyunsaturated fatty acids and steroid hormones as well as to peroxisome proliferators but not to n-alkanes, and it was not repressed by glucose. Both elements mediated activation by oleic acid. Mutational analysis demonstrated that three CCG sequences in CRE2 were critical to the activation by clofibrate as well as to the in vitro binding of a specific protein to this element. These findings suggest that ALK2 is induced by peroxisome proliferators and steroid hormones through a specific CRE2-mediated regulatory mechanism

  18. The contributions of Hans-Dieter Rösler: pioneer of digit ratio (2D:4D) research.

    Science.gov (United States)

    Voracek, Martin; Dressler, Stefan G; Loibl, Lisa Mariella

    2008-12-01

    Over the past decade, the second-to-fourth digit ratio (2D:4D), a putative biomarker for the organizational (permanent) effects of prenatal androgens on the human brain, body, and behavior, has received extensive research attention in psychology. This account makes more widely accessible the contributions of the German psychologist, Hans-Dieter Rösler, an early, for a long time unnoticed, predecessor of modern 2D:4D research. In the mid-1950s, Rösler collected a massive sample of hand outline drawings, totalling nearly 7,000 individuals, ranging in age from 1 mo. to 70 yr. With regard to the distal finger-extent pattern, Rösler differentiated radial (longer index than ring finger), ulnar (reversed pattern), and intermediate hand types, which reflect higher (more female-typical), lower (more male-typical), and intermediate 2D:4D, respectively. Here is summarized Rösler's research. In a series of investigations into the hand types, he reported on their anatomical bases, unsuitability for paternity testing, developmental changes, heritability, sex, side, and occupational group differences, and associations with left-handedness, manual dexterity, mental retardation, and clinodactyly. Based on new data from 313 male and 316 female adults, hand type is further shown to be only a weak proxy of actual 2D:4D, leaving 75% of the interindividual variation in 2D:4D unexplained. Notwithstanding these shortcomings of the hand-type method, Rösler's work from the 1950s still has the potential to inform modern 2D:4D research, as it contains a multitude of testable hypotheses not yet picked up by current research.

  19. [Use of the 2D:4D digit ratio as a biological marker of specific language disorders].

    Science.gov (United States)

    Font-Jordà, Antònia; Gamundí, Antoni; Nicolau Llobera, María Cristina; Aguilar-Mediavilla, Eva

    2018-04-03

    The finding of biological markers of specific language impairment would facilitate their detection and early intervention. In this sense, the 2D:4D finger ratio is considered an indirect indicator of prenatal exposure to testosterone. Previous studies have related it to linguistic competence and aggressive behaviour, and could be a candidate for a biological marker of language impairment. The aim was to compare the value of the 2D:4D ratio in children with Specific Language Impairment (SLI) with those of children with typical language development, as well as to establish to what extent this biological index correlates with the behaviour (linguistic, cognitive, social,...) in both groups. 2D:4D ratio, language, cognition and social behaviour were compared in a group of children with SLI (n=15), with a group of children without language difficulties (n=16) of the same age (between 5-8 years), gender (male), and socio-cultural level. Children with SLI showed significantly higher values of 2D:4D ratio of the right hand, and a negative correlation between this ratio and their linguistic competence. Although the children with SLI showed impaired adaptive abilities, but not more aggressive behaviour, these measurements did not correlate with the 2D:4D index. Nevertheless, social behaviour correlated with language and cognition competence. A higher value of the biological 2D:4D ration (lower intrauterine exposure to testosterone) seems to be associated with language difficulties in boys with SLI, but not with their behavioural difficulties. Their behavioural difficulties seem to be a consequence of their linguistic difficulties and their level of cognition. Copyright © 2018. Publicado por Elsevier España, S.L.U.

  20. 232Th(d,4n)230Pa cross-section measurements at ARRONAX facility

    International Nuclear Information System (INIS)

    Duchemin, C.; Guertin, A.; Metivier, V.; Haddad, F.

    2015-01-01

    Full text of publication follows. The ARRONAX cyclotron [Ref.1], acronym for 'Accelerator for Research in Radiochemistry and Oncology at Nantes Atlantique' is a new facility installed in Nantes, France. A dedicated program has been launched on production of innovative radionuclides for PET imaging and for β- and α- targeted radiotherapy using proton or α particle. Since the accelerator is also able to deliver deuteron beams up to 35 MeV, we have reconsidered the possibility to use them to produce medical isotopes. In this study, we have focused on cross section measurements using the stacked-foil technique [Ref. 2] of one isotope dedicated to alpha radio-immunotherapy (α RIT) [Ref.3], 226 Th which can be produced through different routes. It's of great interest since it has been found to be a more potent alpha particle emitter for leukemia therapies than Bi 213 [Ref.4]. Indeed, the 226 Th decay produced a cascade of four α particles with a cumulated energy of 27.7 MeV. An additional interest is the possible use of a radionuclide generator system 230 U/ 226 Th. 230 U could be produced directly via 231 Pa(p, 2n) 230 U, and indirectly via 230 Pa using proton or deuteron beams through 232 Th(p, 3n) 230 Pa → 230 U, 232 Th(d, 4n) 230 Pa → 230 U. Twelve data sets are published concerning the 230 Pa cross section induced by proton [Ref 5], only one by deuteron [Ref.6]. As sometimes deuteron induced reaction gives higher cross section values, it seems interesting to focus our study on their use as projectile on 232 Th target to produce 230 Pa. Contaminants created during irradiation are also measured since a good optimization of the process is supposed to find the best compromise between production yield and purity of the final product. Our new sets of data are compared with the existing data [Refs.5,6] on other existing production routes and with results given by TALYS code calculations [Ref.7]. References: 1] F. Haddad and al., Eur. J. Med. Mol

  1. Dopamine receptor D4 internalization requires a beta-arrestin and a visual arrestin.

    Science.gov (United States)

    Deming, Janise D; Shin, Jung-A; Lim, Kayleen; Lee, Eun-Jin; Van Craenenbroeck, Kathleen; Craft, Cheryl Mae

    2015-10-01

    The G-protein coupled receptor (GPCR) Dopamine Receptor D4 (DRD4) plays an essential role in cAMP regulation and gap junctional coupling in the photoreceptors, where DRD4 expression is under circadian control. Previous in vitro transfection studies of human DRD4 desensitization have reported that DRD4 is not internalized upon dopamine stimulation when beta-arrestin is co-transfected with DRD4. We hypothesized that the visual arrestins, ARR1 and ARR4, play a modulatory role in DRD4 desensitization in the photoreceptors. To test this hypothesis, immunohistochemistry analysis of mouse retinas was used to determine the cellular localization of beta-arrestins and DRD4 in photoreceptors. In vitro studies were performed in HEK293T cells transiently transfected with human DRD4 and arrestins. First, co-immunoprecipitation experiments were executed to test protein-protein interactions and to investigate the effect of dopamine stimulation. Second, immunohistochemistry analysis was implemented to study DRD4 internalization and translocation of ARR4. Immunohistochemistry studies of mouse retinas confirmed the expression of beta-arrestin 2, ARR1 and ARR4, as well as DRD4 in mouse cone photoreceptor inner segments. Co-immunoprecipitation experiments revealed a dopamine-dependent protein-protein interaction between human DRD4 and ARR4. In vitro internalization experiments showed that no detectable internalization of DRD4 was observed with any single arrestin co-transfected. However, a dopamine-dependent internalization of DRD4 was observed with three out of six sets of two arrestins co-transfected with DRD4. Each of these pairs of arrestins contained one visual arrestin and one beta-arrestin, and no internalization was observed with either two visual arrestins or two beta-arrestins. Additional time-course experiments revealed that in vitro, ARR4 translocates to co-localize with DRD4 at the plasma membrane in response to 30min of dopamine stimulation. The results have functional

  2. Characterization of antimicrobial substance from Lactobacillus salivarius KL-D4 and its application as biopreservative for creamy filling.

    Science.gov (United States)

    Therdtatha, Phatthanaphong; Tandumrongpong, Chanabhorn; Pilasombut, Komkhae; Matsusaki, Hiromi; Keawsompong, Suttipun; Nitisinprasert, Sunee

    2016-01-01

    Lactobacillus salivarius KL-D4 isolated from duck intestine produced bacteriocin which was stable at high temperature and a wide pH range of 3-10. Its cell free supernatant at pH 5.5 exhibited wide inhibitory spectrum against both G+ and G- bacteria. The highest bacteriocin production was obtained in MRS broth supplemented with 0.5 % (w/v) CaCO3 at 6 h by gentle shaking. PCR walking using specific primers at the conserved region of class-II bacteriocin resulted in 4 known genes of kld1, kld2, kld3 and kld4 with 100 % similarity to genes encoding for salivaricin α, β, induction peptide and histidine protein kinase of Lb. salivarius GJ-24 which did not previously report for bacteriocin characterization, while showing 94, 93, 59 and 62 % to other salivaricin gene cluster, respectively. The high activities of 25,600 AU/ml indicated a strong induction peptide expressed by kld3 which has low similarity to previous inducer reported. Based on operon analysis, only kld1, kld3 and kld4 could be expressed and subsequently elucidated that only salivaricin α like bacteriocin was produced and secreted out of the cells. Using protein purification, only a single peptide band obtained showed that this strain produced one bacteriocin which could be salivaricin α namely salivaricin KLD showing about 4.3 kDa on SDS-PAGE. Partial purification by 20 % ammonium sulfate precipitation of the product was tested on the artificial contamination of creamy filling by Bacillus cereus, Enterococcus faecalis, Pseudomonas stutzeri, Staphylococcus sp. and Stenotrophomonas sp. resulting the growth inhibitory efficiency of 4.45-66.9, 11.5-100, 100, 0-28.1 and 5-100 % respectively. Therefore, salivaricin KLD can be a tentative biopreservative for food industry in the future.

  3. Identification of leukotriene D4 specific binding sites in the membrane preparation isolated from guinea pig lung

    International Nuclear Information System (INIS)

    Mong, S.; Wu, H.L.; Clark, M.A.; Stadel, J.M.; Gleason, J.G.; Crooke, S.T.

    1984-01-01

    A radioligand binding assay has been established to study leukotriene specific binding sites in the guinea pig and rabbit tissues. Using high specific activity [ 3 H]-leukotriene D4 [( 3 H]-LTD4), in the presence or absence of unlabeled LTD4, the diastereoisomer of LTD4 (5R,6S-LTD4), leukotriene E4 (LTE4) and the end-organ antagonist, FPL 55712, the authors have identified specific binding sites for [ 3 H]-LTD4 in the crude membrane fraction isolated from guinea pig lung. The time required for [ 3 H]-LTD4 binding to reach equilibrium was approximately 20 to 25 min at 37 degrees C in the presence of 10 mM Tris-HCl buffer (pH 7.5) containing 150 mM NaCl. The binding of [ 3 H]-LTD4 to the specific sites was saturable, reversible and stereospecific. The maximal number of binding sites (Bmax), derived from Scatchard analysis, was approximately 320 +/- 200 fmol per mg of crude membrane protein. The dissociation constants, derived from kinetic and saturation analyses, were 9.7 nM and 5 +/- 4 nM, respectively. The specific binding sites could not be detected in the crude membrane fraction prepared from guinea pig ileum, brain and liver, or rabbit lung, trachea, ileum and uterus. In radioligand competition experiments, LTD4, FPL 55712 and 5R,6S-LTD4 competed with [ 3 H]-LTD4. The metabolic inhibitors of arachidonic acid and SKF 88046, an antagonist of the indirectly-mediated actions of LTD4, did not significantly compete with [ 3 H]-LTD4 at the specific binding sites. These correlations indicated that these specific binding sites may be the putative leukotriene receptors in the guinea-pig lung

  4. Inkjet-/3D-/4D-printed autonomous wearable RF modules for biomonitoring, positioning and sensing applications

    Science.gov (United States)

    Bito, Jo; Bahr, Ryan; Hester, Jimmy; Kimionis, John; Nauroze, Abdullah; Su, Wenjing; Tehrani, Bijan; Tentzeris, Manos M.

    2017-05-01

    In this paper, numerous inkjet-/3D-/4D-printed wearable flexible antennas, RF electronics, modules and sensors fabricated on paper and other polymer (e.g. LCP) substrates are introduced as a system-level solution for ultra-low-cost mass production of autonomous Biomonitoring, Positioning and Sensing applications. This paper briefly discusses the state-of-the-art area of fully-integrated wearable wireless sensor modules on paper or flexible LCP and show the first ever 4D sensor module integration on paper, as well as numerous 3D and 4D multilayer paper-based and LCP-based RF/microwave, flexible and wearable structures, that could potentially set the foundation for the truly convergent wireless sensor ad-hoc "on-body networks of the future with enhanced cognitive intelligence and "rugged" packaging. Also, some challenges concerning the power sources of "nearperpetual" wearable RF modules, including flexible miniaturized batteries as well as power-scavenging approaches involving electromagnetic and solar energy forms are discuessed. The final step of the paper will involve examples from mmW wearable (e.g. biomonitoring) antennas and RF modules, as well as the first examples of the integration of inkjet-printed nanotechnology-based (e.g.CNT) sensors on paper and organic substrates for Internet of Things (IoT) applications. It has to be noted that the paper will review and present challenges for inkjetprinted organic active and nonlinear devices as well as future directions in the area of environmentally-friendly "green") wearable RF electronics and "smart-skin conformal sensors.

  5. Counselor Identity: Conformity or Distinction?

    Science.gov (United States)

    McLaughlin, Jerry E.; Boettcher, Kathryn

    2009-01-01

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

  6. El Naschie's ε (∞) space-time and scale relativity theory in the topological dimension D = 4

    International Nuclear Information System (INIS)

    Agop, M.; Murgulet, C.

    2007-01-01

    In the topological dimension D = 4 of the scale relativity theory, the self-structuring of a coherent quantum fluid implies the Golden mean renormalization group. Then, the transfinite set of El Naschie's ε (∞) space-time becomes the background of a new physics (the transfinite physics)

  7. The Dutch Technical-Tactical Tennis Test (D4T) for Talent Identification and Development : Psychometric Characteristics

    NARCIS (Netherlands)

    Kolman, Nikki; Huijgen, Barbara; Kramer, Tamara; Elferink-Gemser, Marije; Visscher, Chris

    2017-01-01

    This study examined the test-retest reliability, validity and feasibility of the newly developed Dutch Technical Tactical Tennis Test (D4T). This new test is relevant for talent identification and development in tennis. Thirty-two youth male tennis players (age 13.4 +/- 0.5) were classified as elite

  8. Fluoride removal from double four-membered ring (D4R) units in As-synthesized Ge-containing zeolites

    KAUST Repository

    Liu, Xiaolong; Ravon, Ugo; Tuel, Alain

    2011-01-01

    Fluoride anions can be removed from the framework of as-prepared Ge-containing zeolites ITQ-13 and ITQ-17 without modification of the crystallinity and crystal habit. By contrast to all-silica ITQ-13 for which fluoride could not get out from D4R

  9. Finite Element Analysis of Stress Distribution in Three Commonly Used Implant Systems in D2 and D4 Bone Densities

    Directory of Open Access Journals (Sweden)

    C Radha

    2016-01-01

    Materials and Methods : Pro-engineer 3-0 software was used to create the geometric models of the three implant systems (Nobel biocare, Biohorizon, Adin and two bone densities D2 and D4. Six 3D models were created to simulate each one of the three implant systems supporting a metal ceramic crown placed in two different densities of bone D2 and D4. The Poisson′s ratio(΅ and Youngs modulus(E of elasticity were assigned to different materials used for the models. Vertical and oblique loads of 450N each were applied on all six models. Von Mises stress analysis was done with ANSYS software. Results : Von Mises stresses were more within D4 type bone than D2 type, for all the three systems of implants and less stresses were seen in Biohorizon implant followed by Nobel Biocare and Adin implant particularly in D4 bone. Conclusion: The study concluded that the selection of a particular implant system should be based on the scientific research rather than on popularity.

  10. Organization of an interphase system for the coupling of WINS-D4 and SNAP-3D programs

    International Nuclear Information System (INIS)

    Frias Suarez, D.

    1989-01-01

    In this report a modular system developed for the CC-1 critical assembly's physical calculation is described. It was based upon the WINS-D4 and SNAP-3D codes, which are coupled by means of an interphase module and a groups diffusion cross sections library

  11. Biological Evaluation of 99mTc-HYNIC-EDDA/tricine-(Ser)-D4 Peptide for Tumor Targeting.

    Science.gov (United States)

    Kazemi, Ziba; Zahmatkesh, Mona Haddad; Abedi, Seyed Mohammad; Hosseinimehr, Seyed Jalal

    2017-08-24

    D4 small peptide (Leu-Ala-Arg-Leu-Leu-Thr) was selected as an appropriate agent for specific targeting of epidermal growth factor receptor (EGFR). The aim of study was to investigate the 99mTc-labeled D4 peptide for non-small cell lung tumor targeting. HYNIC-(Ser)3-D4 peptide was labeled with 99mTc using mixture of tricine and ethylenediamine diacetic acid (EDDA) as co-ligands. The in vitro cellular uptake of radiolabeled peptide was evaluated by blocking test on human non-small cell lung cancer (A-549) cell line and its biodistribution was evaluated in A-549 xenografted nude mice. This conjugated peptide was labeled with 99mTc in high radiochemical purity and it was highly stable in buffer and serum. The un-blocked to blocked cellular radioactivity ratio was 4- fold that showed a specific binding of this radiolabeled peptide on A-549 cell. Animal biodistribution in A-549 xenografted nude mice showed rapid clearance from blood and other non-target organs. Tumor uptake values as %ID/g (percentage of injection dose per gram of tissue) were 2.47% and 1.30% at 1 and 4 h after injection. This study showed the 99mTc-EDDA/tricine-HYNIC-(Ser)3-D4 peptide had tumor targeting on the non-small cell lung tumor. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. The Ratio of Second to Fourth Digit Length (2D:4D in Children with Autistic Disorder

    Directory of Open Access Journals (Sweden)

    Javad Baharara

    2014-11-01

    Full Text Available Introduction Emerging hypotheses suggest a causal role for prenatal androgen exposure in some cases of Autism spectrum disorders (ASD. The ratios of the lengths of the bones of the 2nd to the 4th digits (2D:4D are purported to be markers for prenatal androgen exposure and to be established early in gestation. Ratio of second and fourth digits (2D:4D  is usually used as a proxy for prenatal testosterone. Methods and Materials In this study, 2D:4D in 48 children with ASD and in 41  control child was measured. Two groups were matched with the gender and age. Both groups were selected by convenience sampling method. All statistical analyses were performed using SPSS 19.0 software, considering as significant less than .05 (p < .05. Results: Results showed that the average ratio of 2D:4D in ASD children were lower than the ratio in control children (P

  13. Prenatal exposure to testosterone (2D:4D) and social hierarchy together predict voice behavior in bankers.

    Science.gov (United States)

    Bijleveld, Erik; Baalbergen, Joost

    2017-01-01

    Prohibitive voice behaviors are employees' expressions of concern about practices, incidents, or behaviors that may potentially harm the organization. In this study, we examined a potential biological correlate of prohibitive voice: prenatal exposure to testosterone. In a sample of bankers, we used 2D:4D (i.e., the ratio of the length of the index finger to the length of the ring finger) as a marker for prenatal exposure to testosterone (lower 2D:4D suggests higher prenatal exposure to testosterone). We used a self-report scale to measure prohibitive voice. For low-ranked employees, lower 2D:4D was related to using less voice. No such relation was found for high-ranked employees. Conclusions should be drawn with caution, because the findings only applied to voice regarding the organization as a whole (and not to voice regarding the own team), and because of methodological limitations. However, the findings are consistent with the ideas that (a) people low in 2D:4D tend to strive to attain and maintain social status and that (b) remaining silent about perceived problems in the organization is-at least for low-ranked employees-a means to achieve this goal.

  14. Symptoms of Attention-Deficit/Hyperactivity Disorder in Down Syndrome: Effects of the Dopamine Receptor D4 Gene

    Science.gov (United States)

    Mason, Gina Marie; Spanó, Goffredina; Edgin, Jamie

    2015-01-01

    This study examined individual differences in ADHD symptoms and executive function (EF) in children with Down syndrome (DS) in relation to the dopamine receptor D4 (DRD4) gene, a gene often linked to ADHD in people without DS. Participants included 68 individuals with DS (7-21 years), assessed through laboratory tasks, caregiver reports, and…

  15. No Association between the 2D:4D Fetal Testosterone Marker and Multidimensional Attentional Abilities in Children with ADHD

    Science.gov (United States)

    Lemiere, Jurgen; Boets, Bart; Danckaerts, Marina

    2010-01-01

    Aim: It has been suggested that high levels of prenatal testosterone exposure are implied in the aetiology of attention-deficit-hyperactivity disorder (ADHD). This study examined the association between the ratio of the length of the second and fourth digits (2D:4D ratio), a marker of fetal testosterone exposure, and the presence of ADHD-related…

  16. Fluoride removal from double four-membered ring (D4R) units in As-synthesized Ge-containing zeolites

    KAUST Repository

    Liu, Xiaolong

    2011-11-22

    Fluoride anions can be removed from the framework of as-prepared Ge-containing zeolites ITQ-13 and ITQ-17 without modification of the crystallinity and crystal habit. By contrast to all-silica ITQ-13 for which fluoride could not get out from D4R units, F is completely removed from Ge rich zeolites, even from D4R cages. This has been explained by the relaxing effect of germanium, making F less necessary for the stabilization of the small D4R units. Si/Ge ratios are similar in as-prepared and treated zeolites, indicating that the framework composition is not affected by the removal of anions. The fluoride-free zeolites possess XRD patterns similar to those of the as-made solids but their 29Si NMR spectra are significantly different, revealing the sensitivity of the method to the environment of silicon atoms in the framework. The extent of fluoride that can be removed from D4R units depends not only on the framework Ge content but also on the zeolite topology: for similar contents, F is much more easily eliminated from ITQ-17 than from ITQ-13. © 2011 American Chemical Society.

  17. Digit ratio (2D:4D) and circulating testosterone, oestradiol, and progesterone levels across the menstrual cycle.

    Science.gov (United States)

    Richards, Gareth; Klimek, Magdalena; Jasienska, Grazyna; Marcinkowska, Urszula M

    2018-02-01

    Digit ratio (2D:4D) is used by researchers as an indicator of prenatal sex hormone exposure. Two previous studies have examined associations between 2D:4D and circulating sex steroid concentrations across the menstrual cycle in adult females. One reported that digit ratio correlated positively with oestradiol levels, whereas the other found no such effect; neither observed significant associations with progesterone. To examine associations between 2D:4D, as well as asymmetry (i.e. right minus left 2D:4D), and circulating sex steroids across the menstrual cycle. Correlational. 32 naturally cycling adult females from rural southern Poland. Salivary oestradiol, progesterone, testosterone, and testosterone to oestradiol ratio (T:O) measured during the follicular, peri-ovulatory, and luteal phases. Average levels across the cycle were also examined. Asymmetry in digit ratio correlated positively with oestradiol at each phase, as well as with average levels across the cycle. Each association, other than that relating to average levels, remained statistically significant after a range of covariates had been controlled for. No other significant correlations were observed between digit ratio variables and circulating hormone levels. Our results might suggest that low exposure to androgens and/or high exposure to oestrogens during gestation is a predictor of high oestradiol levels in naturally cycling females of reproductive age. However, considering that it was asymmetry in digit ratio, and not either right or left 2D:4D, that was a significant predictor, it is also possible that these effects reflect more general associations between bilateral asymmetry and circulating oestradiol levels. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. FURTHER EVIDENCE OF AN ASSOCIATION BETWEEN LOW SECOND-TO-FOURTH DIGIT RATIO (2D:4D) AND SELECTION FOR THE UNIFORMED SERVICES: A STUDY AMONG POLICE PERSONNEL IN WROCŁAW, POLAND.

    Science.gov (United States)

    Kozieł, Sławomir; Kociuba, Marek; Chakraborty, Raja; Sitek, Aneta; Ignasiak, Zofia

    2017-08-22

    Males and females differ in their preference for occupations and sporting activities, and differ also in risk-taking attitudes. In addition to other explanations, prenatal hormone exposure has been implicated in these gender-associated differences. The ratio of the relative lengths of the second-to-fourth digits (2D:4D) is a proxy indicator of prenatal exposure to testosterone relative to oestrogen. The 2D:4D ratio has been found to be associated with choice of occupation, particularly among females. This study investigated whether 2D:4D differed between police officers and a control group of civilians in Wrocław, Poland. Participants were 147 male and 55 female police officers and 91 male and 75 female civilian controls. The police officers had to undergo rigorous physical ability tests during recruitment and their job bore relatively higher risk, whereas the controls had a normal civilian lifestyle. Height, weight, hand grip strength and lengths of the second and fourth digits were measured. Analyses of variance and covariance were employed to assess the significance of difference in digit ratio between groups (police officers and civilians) allowing for interaction with sex. The policewomen, compared with the female controls, were taller and had stronger hand grip strength, but had lower 2D:4D in the right hand and average 2D:4D of both hands. However, male and female police officers slightly differed only in the right hand digit ratio but not in the left hand ratio or the average for the two hands. However, the control group showed significant sex differences in all digit ratios with higher (feminine) mean values in females. The study provides further evidence that prenatal testosterone exposure, as reflected in the 2D:4D ratio, might have an association with choice of occupation, particularly among females.

  19. Structures and Biogenesis of Fallaxosides D4, D5, D6 and D7, Trisulfated Non-Holostane Triterpene Glycosides from the Sea Cucumber Cucumaria fallax

    Directory of Open Access Journals (Sweden)

    Alexandra S. Silchenko

    2016-07-01

    Full Text Available Four new trisulfated triterpene glycosides, fallaxosides D4 (1, D5 (2, D6 (3 and D7 (4 have been isolated from the sea cucumber Cucumaria fallax (Cucumariidae, Dendrochirotida. The structures of the glycosides have been elucidated by 2D NMR spectroscopy and HRESIMS. All the glycosides have the lanostane aglycones of a rare non-holostane type with 7(8-, 8(9- or 9(11-double bonds, one or two hydroxyl groups occupying unusual positions in the polycyclic nucleus and shortened or normal side chains. The pentasaccharide carbohydrate moieties of 1–4 have three sulfate groups. The cytotoxic activity of glycosides 1–4 against the ascite form of mouse Ehrlich carcinoma cells and mouse spleen lymphocytes and hemolytic activity against mouse erythrocytes have been studied.

  20. Studies of alpha-helicity and intersegmental interactions in voltage-gated Na+ channels: S2D4.

    Directory of Open Access Journals (Sweden)

    Zhongming Ma

    2009-11-01

    Full Text Available Much data, including crystallographic, support structural models of sodium and potassium channels consisting of S1-S4 transmembrane segments (the "voltage-sensing domain" clustered around a central pore-forming region (S5-S6 segments and the intervening loop. Voltage gated sodium channels have four non-identical domains which differentiates them from the homotetrameric potassium channels that form the basis for current structural models. Since potassium and sodium channels also exhibit many different functional characteristics and the fourth domain (D4 of sodium channels differs in function from other domains (D1-D3, we have explored its structure in order to determine whether segments in D4 of sodium channels differ significantly from that determined for potassium channels. We have probed the secondary and tertiary structure and the role of the individual amino acid residues of the S2D4 of Na(v1.4 by employing cysteine-scanning mutagenesis (with tryptophan and glutamine substituted for native cysteine. A Fourier transform power spectrum of perturbations in free energy of steady-state inactivation gating (using midpoint potentials and slopes of Boltzmann equation fits of channel availability, h(infinity-V plots indicates a substantial amount of alpha-helical structure in S2D4 (peak at 106 degrees, alpha-Periodicity Index (alpha-PI of 3.10, This conclusion is supported by alpha-PI values of 3.28 and 2.84 for the perturbations in rate constants of entry into (beta and exit from (alpha fast inactivation at 0 mV for mutant channels relative to WT channels assuming a simple two-state model for transition from the open to inactivated state. The results of cysteine substitution at the two most sensitive sites of the S2D4 alpha-helix (N1382 and E1392C support the existence of electrostatic network interactions between S2 and other transmembrane segments within Na(v1.4D4 similar to but not identical to those proposed for K+ channels.

  1. Distinction

    OpenAIRE

    2010-01-01

    Pr Serge Haroche La Médaille d’or 2009 du CNRS est décernée au Pr Serge Haroche, titulaire de la chaire de Physique quantique depuis 2001. Serge Haroche est spécialiste de physique atomique et d’optique quantique. Il est l’un des fondateurs de l’électrodynamique quantique en cavité, domaine qui permet, par des expériences conceptuellement simples, d’éclairer les fondements de la théorie quantique et de réaliser des prototypes de systèmes de traitement quantique de l’information. Serge Haroche...

  2. Fuzzy Killing spinors and supersymmetric D4 action on the fuzzy 2-sphere from the ABJM model

    International Nuclear Information System (INIS)

    Nastase, Horatiu; Papageorgakis, Constantinos

    2009-01-01

    Our recent construction arXiv:0903.3966 for the fuzzy 2-sphere in terms of bifundamentals, discovered in the context of the ABJM model, is shown to be explicitly equivalent to the usual (adjoint) fuzzy sphere construction. The matrices G-tilde α that define it play the role of fuzzy Killing spinors on the 2-sphere, out of which all spherical harmonics are constructed. Starting from the quadratic fluctuation action around these solutions in the mass-deformed ABJM theory, we recover a supersymmetric D4-brane action wrapping a 2-sphere, including fermions. We obtain both the usual D4 action with an unusual x-dependence on the sphere, as well as a twisted version in terms of the usual x-dependence, and contrast our result with the Maldacena-Nunez case of a D5 wrapping an S 2 . The twisted and unwisted fields are related by the same matrix G-tilde α .

  3. Calculation analysis of Wims/D4-Batan-2DIFF neutron spectrum on RSG-GAS with cadmium ratio

    International Nuclear Information System (INIS)

    Radianti, I.B.; Zuhair; Hamzah, A.

    1998-01-01

    The calculation analysis of WIMS/D4-BATAN-2DIFF neutron spectrum was performed by comparison the calculation result of cadmium ratio with the experiment result on CIP, IP2, IP3 and IP4 irradiation positions of RSG GAS tenth core. The foils of Au, Mn and Co were used for determination of the measured and calculated cadmium ratios. Spectrum calculation was done in 69 energy group with 541 energy group (till 10 MeV) cross section of foil absorption reaction. The difference values between cadmium ratio calculation and experiment result for all cases were in interval of 11.0%-26.3% which are out of measurement deviation range. From these result, it concluded that the use of WIM /D4 in generating group constant is not sufficient to obtain the neutron spectrum, especially for non-fuel region

  4. 3d-4f magnetic interaction with density functional theory plus u approach: local Coulomb correlation and exchange pathways.

    Science.gov (United States)

    Zhang, Yachao; Yang, Yang; Jiang, Hong

    2013-12-12

    The 3d-4f exchange interaction plays an important role in many lanthanide based molecular magnetic materials such as single-molecule magnets and magnetic refrigerants. In this work, we study the 3d-4f magnetic exchange interactions in a series of Cu(II)-Gd(III) (3d(9)-4f(7)) dinuclear complexes based on the numerical atomic basis-norm-conserving pseudopotential method and density functional theory plus the Hubbard U correction approach (DFT+U). We obtain improved description of the 4f electrons by including the semicore 5s5p states in the valence part of the Gd-pseudopotential. The Hubbard U correction is employed to treat the strongly correlated Cu-3d and Gd-4f electrons, which significantly improve the agreement of the predicted exchange constants, J, with experiment, indicating the importance of accurate description of the local Coulomb correlation. The high efficiency of the DFT+U approach enables us to perform calculations with molecular crystals, which in general improve the agreement between theory and experiment, achieving a mean absolute error smaller than 2 cm(-1). In addition, through analyzing the physical effects of U, we identify two magnetic exchange pathways. One is ferromagnetic and involves an interaction between the Cu-3d, O-2p (bridge ligand), and the majority-spin Gd-5d orbitals. The other one is antiferromagnetic and involves Cu-3d, O-2p, and the empty minority-spin Gd-4f orbitals, which is suppressed by the planar Cu-O-O-Gd structure. This study demonstrates the accuracy of the DFT+U method for evaluating the 3d-4f exchange interactions, provides a better understanding of the exchange mechanism in the Cu(II)-Gd(III) complexes, and paves the way for exploiting the magnetic properties of the 3d-4f compounds containing lanthanides other than Gd.

  5. Some results on the eigenfunctions of the quantum trigonometric Calogero-Sutherland model related to the Lie algebra D4

    International Nuclear Information System (INIS)

    Fernandez Nunez, J.; Garcia Fuertes, W.; Perelomov, A.M.

    2003-01-01

    We express the Hamiltonian of the quantum trigonometric Calogero-Sutherland model related to the Lie algebra D 4 in terms of a set of Weyl-invariant variables, namely, the characters of the fundamental representations of the Lie algebra. This parametrization allows us to solve for the energy eigenfunctions of the theory and to study properties of the system of orthogonal polynomials associated with them such as recurrence relations and generating functions

  6. Can digit ratio (2D:4D) studies be helpful in explaining the aetiology of idiopathic gynecomastia?

    Science.gov (United States)

    Kasielska-Trojan, Anna; Antoszewski, Bogusław

    2015-01-01

    Aetiology of idiopathic form of gynecomastia is unknown and it has not been established if it is related to factors present at the prenatal period or if it is caused by yet unidentified environmental conditions. The aim of this study is to compare digit ratio (2D:4D) in men with idiopathic gynecomastia and unaffected male and female controls from the general population. The study involved 250 subjects (50 men with idiopathic gynecomastia, 100 control men and 100 control women). Eight measurements were taken: body height, waist and hip circumferences, II and IV digits' lengths (right and left), and body weight, and 4 indices were calculated: BMI, WHR, and 2D:4D for the right and left hand. 2D:4D in men with gynecomastia ([median (I-III quartiles)]: 1.03 (1.01-1.04) for right hand and 1.03 (1.01-1.03) for left hand) was significantly different than the ratio in control men [0.97 (0.95-0.99)] for right and left hand) (pgynecomastia were characterized with higher values of the following variables: weight, waist and hip circumferences, BMI and WHR. Their body height was significantly greater than in women (pgynecomastia and justify introducing the new group: "gynecomastia related to the prenatal sex hormones disturbances". Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Hidden role of Maxwell superalgebras in the free differential algebras of D = 4 and D = 11 supergravity

    Science.gov (United States)

    Ravera, Lucrezia

    2018-03-01

    The purpose of this paper is to show that the so-called Maxwell superalgebra in four dimensions, which naturally involves the presence of a nilpotent fermionic generator, can be interpreted as a hidden superalgebra underlying N=1, {D}=4 supergravity extended to include a 2-form gauge potential associated to a 2-index antisymmetric tensor. In this scenario, the theory is appropriately discussed in the context of Free Differential Algebras (an extension of the Maurer-Cartan equations to involve higher-degree differential forms). The study is then extended to the Free Differential Algebra describing D = 11 supergravity, showing that, also in this case, there exists a super-Maxwell algebra underlying the theory. The same extra spinors dual to the nilpotent fermionic generators whose presence is crucial for writing a supersymmetric extension of the Maxwell algebras, both in the D = 4 and in the D = 11 case, turn out to be fundamental ingredients also to reproduce the D = 4 and D = 11 Free Differential Algebras on ordinary superspace, whose basis is given by the supervielbein. The analysis of the gauge structure of the supersymmetric Free Differential Algebras is carried on taking into account the gauge transformations from the hidden supergroup-manifold associated with the Maxwell superalgebras.

  8. Defining poverty as distinctively human

    Directory of Open Access Journals (Sweden)

    H.P.P. Lötter

    2007-05-01

    Full Text Available While it is relatively easy for most people to identify human beings suffering from poverty, it is rather more difficult to come to a proper understanding of poverty. In this article the author wants to deepen our understanding of poverty by interpreting the conventional definitions of poverty in a new light. The article starts with a defence of a claim that poverty is a concept uniquely applicable to humans. It then present a critical discussion of the distinction between absolute and relative poverty and it is then argued that a revision of this distinction can provide general standards applicable to humans everywhere.

  9. Nitrogen-responsive Regulation of GATA Protein Family Activators Gln3 and Gat1 Occurs by Two Distinct Pathways, One Inhibited by Rapamycin and the Other by Methionine Sulfoximine*

    Science.gov (United States)

    Georis, Isabelle; Tate, Jennifer J.; Cooper, Terrance G.; Dubois, Evelyne

    2011-01-01

    Nitrogen availability regulates the transcription of genes required to degrade non-preferentially utilized nitrogen sources by governing the localization and function of transcription activators, Gln3 and Gat1. TorC1 inhibitor, rapamycin (Rap), and glutamine synthetase inhibitor, methionine sulfoximine (Msx), elicit responses grossly similar to those of limiting nitrogen, implicating both glutamine synthesis and TorC1 in the regulation of Gln3 and Gat1. To better understand this regulation, we compared Msx- versus Rap-elicited Gln3 and Gat1 localization, their DNA binding, nitrogen catabolite repression-sensitive gene expression, and the TorC1 pathway phosphatase requirements for these responses. Using this information we queried whether Rap and Msx inhibit sequential steps in a single, linear cascade connecting glutamine availability to Gln3 and Gat1 control as currently accepted or alternatively inhibit steps in two distinct parallel pathways. We find that Rap most strongly elicits nuclear Gat1 localization and expression of genes whose transcription is most Gat1-dependent. Msx, on the other hand, elicits nuclear Gln3 but not Gat1 localization and expression of genes that are most Gln3-dependent. Importantly, Rap-elicited nuclear Gln3 localization is absolutely Sit4-dependent, but that elicited by Msx is not. PP2A, although not always required for nuclear GATA factor localization, is highly required for GATA factor binding to nitrogen-responsive promoters and subsequent transcription irrespective of the gene GATA factor specificities. Collectively, our data support the existence of two different nitrogen-responsive regulatory pathways, one inhibited by Msx and the other by rapamycin. PMID:22039046

  10. Nitrogen-responsive regulation of GATA protein family activators Gln3 and Gat1 occurs by two distinct pathways, one inhibited by rapamycin and the other by methionine sulfoximine.

    Science.gov (United States)

    Georis, Isabelle; Tate, Jennifer J; Cooper, Terrance G; Dubois, Evelyne

    2011-12-30

    Nitrogen availability regulates the transcription of genes required to degrade non-preferentially utilized nitrogen sources by governing the localization and function of transcription activators, Gln3 and Gat1. TorC1 inhibitor, rapamycin (Rap), and glutamine synthetase inhibitor, methionine sulfoximine (Msx), elicit responses grossly similar to those of limiting nitrogen, implicating both glutamine synthesis and TorC1 in the regulation of Gln3 and Gat1. To better understand this regulation, we compared Msx- versus Rap-elicited Gln3 and Gat1 localization, their DNA binding, nitrogen catabolite repression-sensitive gene expression, and the TorC1 pathway phosphatase requirements for these responses. Using this information we queried whether Rap and Msx inhibit sequential steps in a single, linear cascade connecting glutamine availability to Gln3 and Gat1 control as currently accepted or alternatively inhibit steps in two distinct parallel pathways. We find that Rap most strongly elicits nuclear Gat1 localization and expression of genes whose transcription is most Gat1-dependent. Msx, on the other hand, elicits nuclear Gln3 but not Gat1 localization and expression of genes that are most Gln3-dependent. Importantly, Rap-elicited nuclear Gln3 localization is absolutely Sit4-dependent, but that elicited by Msx is not. PP2A, although not always required for nuclear GATA factor localization, is highly required for GATA factor binding to nitrogen-responsive promoters and subsequent transcription irrespective of the gene GATA factor specificities. Collectively, our data support the existence of two different nitrogen-responsive regulatory pathways, one inhibited by Msx and the other by rapamycin.

  11. First comparative characterization of three distinct ferritin subunits from a teleost: Evidence for immune-responsive mRNA expression and iron depriving activity of seahorse (Hippocampus abdominalis) ferritins.

    Science.gov (United States)

    Oh, Minyoung; Umasuthan, Navaneethaiyer; Elvitigala, Don Anushka Sandaruwan; Wan, Qiang; Jo, Eunyoung; Ko, Jiyeon; Noh, Gyeong Eon; Shin, Sangok; Rho, Sum; Lee, Jehee

    2016-02-01

    Ferritins play an indispensable role in iron homeostasis through their iron-withholding function in living beings. In the current study, cDNA sequences of three distinct ferritin subunits, including a ferritin H, a ferritin M, and a ferritin L, were identified from big belly seahorse, Hippocampus abdominalis, and molecularly characterized. Complete coding sequences (CDS) of seahorse ferritin H (HaFerH), ferritin M (HaFerM), and ferritin L (HaFerL) subunits were comprised of 531, 528, and 522 base pairs (bp), respectively, which encode polypeptides of 177, 176, and 174 amino acids, respectively, with molecular masses of ∼20-21 kDa. Our in silico analyses demonstrate that these three ferritin subunits exhibit the typical characteristics of ferritin superfamily members including iron regulatory elements, domain signatures, and reactive centers. The coding sequences of HaFerH, M, and L were cloned and the corresponding proteins were overexpressed in a bacterial system. Recombinantly expressed HaFer proteins demonstrated detectable in vivo iron sequestrating (ferroxidase) activity, consistent with their putative iron binding capability. Quantification of the basal expression of these three HaFer sequences in selected tissues demonstrated a gene-specific ubiquitous spatial distribution pattern, with abundance of mRNA in HaFerM in the liver and predominant expression of HaFerH and HaFerL in blood. Interestingly, the basal expression of all three ferritin genes was found to be significantly modulated against pathogenic stress mounted by lipopolysaccharides (LPS), poly I:C, Streptococcus iniae, and Edwardsiella tarda. Collectively, our findings suggest that the three HaFer subunits may be involved in iron (II) homeostasis in big belly seahorse and that they are important in its host defense mechanisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Learning process for performing and analyzing 3D/4D transperineal ultrasound imaging and interobserver reliability study.

    Science.gov (United States)

    Siafarikas, F; Staer-Jensen, J; Braekken, I H; Bø, K; Engh, M Ellström

    2013-03-01

    To evaluate the learning process for acquiring three- and four-dimensional (3D/4D) transperineal ultrasound volumes of the levator hiatus (LH) dimensions at rest, during pelvic floor muscle (PFM) contraction and on Valsalva maneuver, and for analyzing the ultrasound volumes, as well as to perform an interobserver reliability study between two independent ultrasound examiners. This was a prospective study including 22 women. We monitored the learning process of an inexperienced examiner (IE) performing 3D/4D transperineal ultrasonography and analyzing the volumes. The examination included acquiring volumes during three PFM contractions and three Valsalva maneuvers. LH dimensions were determined in the axial plane. The learning process was documented by estimating agreement between the IE and an experienced examiner (E) using the intraclass correlation coefficient. Agreement was calculated in blocks of 10 ultrasound examinations and analyzed volumes. After the learning process was complete the interobserver reliability for the technique was calculated between these two independent examiners. For offline analysis of the first 10 ultrasound volumes obtained by E, good to very good agreement between E and IE was achieved for all LH measurements except for the left and right levator-urethra gap and pubic arc. For the next 10 analyzed volumes, agreement improved for all LH measurements. Volumes that had been obtained by IE and E were then re-evaluated by IE, and good to very good agreement was found for all LH measurements indicating consistency in volume acquisition. The interobserver reliability study showed excellent ICC values (ICC, 0.81-0.97) for all LH measurements except the pubic arc (ICC = 0.67). 3D/4D transperineal ultrasound is a reliable technique that can be learned in a short period of time. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

  13. The Dutch Technical-Tactical Tennis Test (D4T for Talent Identification and Development: Psychometric Characteristics

    Directory of Open Access Journals (Sweden)

    Kolman Nikki

    2017-01-01

    Full Text Available This study examined the test-retest reliability, validity and feasibility of the newly developed Dutch Technical-Tactical Tennis Test (D4T. This new test is relevant for talent identification and development in tennis. Thirty-two youth male tennis players (age 13.4 ± 0.5 were classified as elite (n = 15 or sub-elite (n = 17 according to their position on the national youth ranking list under 15 years (cut-off rank 50 in the Netherlands. Games, rallies and different tactical situations (i.e. offensive, neutral and defensive were simulated with a ball machine. Players had to return 72 balls to predetermined target areas. Stroke quality was recorded based on ball velocity and accuracy (VA-index, as well as percentage errors. Test-retest reliability was assessed by comparing differences between the first and second test-session (n = 10. An intraclass-correlation coefficient of .78 for the VA-index was found (p < .05, indicating excellent test-retest reliability. Independent t-tests revealed that elite players outscored sub-elite players for the VA-index, ball velocity, accuracy and percentage errors (p < .05, supporting good validity. Furthermore, a high correlation was found between the VA-index and individual positions on the youth ranking list (p = -.75; p < .001. The assessment of feasibility indicated that the D4T was applicable for instructors and coaches. In conclusion, the D4T was shown to be a reliable, valid and feasible test to measure technical-tactical characteristics of tennis performance in youth players.

  14. BPS black holes in a non-homogeneous deformation of the stu model of N=2, D=4 gauged supergravity

    Energy Technology Data Exchange (ETDEWEB)

    Klemm, Dietmar [Dipartimento di Fisica, Università di Milano, and INFN - Sezione di Milano,Via Celoria 16, I-20133 Milano (Italy); Marrani, Alessio [Centro Studi e Ricerche ‘Enrico Fermi’, Via Panisperna 89A, I-00184 Roma (Italy); Dipartimento di Fisica e Astronomia ‘Galileo Galilei’, Università di Padova, and INFN - Sezione di Padova,Via Marzolo 8, I-35131 Padova (Italy); Petri, Nicolò; Santoli, Camilla [Dipartimento di Fisica, Università di Milano, and INFN - Sezione di Milano,Via Celoria 16, I-20133 Milano (Italy)

    2015-09-29

    We consider a deformation of the well-known stu model of N=2, D=4 supergravity, characterized by a non-homogeneous special Kähler manifold, and by the smallest electric-magnetic duality Lie algebra consistent with its upliftability to five dimensions. We explicitly solve the BPS attractor equations and construct static supersymmetric black holes with radial symmetry, in the context of U(1) dyonic Fayet-Iliopoulos gauging, focussing on axion-free solutions. Due to non-homogeneity of the scalar manifold, the model evades the analysis recently given in the literature. The relevant physical properties of the resulting black hole solution are discussed.

  15. Remaining Sites Verification Package for the 1607-D4 Septic System. Attachment to Waste Site Reclassification Form 2005-036

    International Nuclear Information System (INIS)

    Carlson, R.A.

    2006-01-01

    The 1607-D4 Septic System was a septic tank and tile field that received sanitary sewage from the 115-D/DR Gas Recirculation Facility. This septic system operated from 1944 to 1968. Decommissioning took place in 1985 and 1986 when all above-grade features were demolished and the tank backfilled. The results of verification sampling demonstrated that residual contaminant concentrations do not preclude any future uses and allow for unrestricted use of shallow zone soils. The results also showed that residual contaminant concentrations are protective of groundwater and the Columbia River

  16. On a phase transition of a Kosterlitz-thouless-type in the d=4, U(1)-lattice gauge theory

    International Nuclear Information System (INIS)

    Marchetti, D.H.U.; Perez, J.F.

    1986-12-01

    The d=4, U(1)-lattice gauge theory with the Villain action may be represented as a locally neutral gas of topological (plaquette) charges which interact via a logarithmically confining potential, is shown. Using this representation a renormalization group analysis to show the existence of a phase transition of the Kosterlitz-Thouless-type was performed. An improved hierarchical version of the model which displays (unlike the usual Migdal-Kadanoff approach) a stable line of gaussian fixed points at low temperatures, which should correspond to the usual deconfining region of these systems is presented. (Author) [pt

  17. Defect in dermatan sulfate in urine of patients with Ehlers-Danlos syndrome caused by a CHST14/D4ST1 deficiency.

    Science.gov (United States)

    Mizumoto, Shuji; Kosho, Tomoki; Hatamochi, Atsushi; Honda, Tomoko; Yamaguchi, Tomomi; Okamoto, Nobuhiko; Miyake, Noriko; Yamada, Shuhei; Sugahara, Kazuyuki

    2017-08-01

    Dermatan sulfate (DS) plays a number of roles in a wide range of biological activities such as cell signaling and tissue morphogenesis through interactions with various extracellular matrix proteins including collagen. Mutations in the carbohydrate sulfotransferase 14 gene (CHST14) encoding CHST14/dermatan 4-O-sulfotransferase-1 (D4ST1), which is responsible for the biosynthesis of DS, cause a recently delineated form of Ehlers-Danlos syndrome (EDS, musculocontractural type 1), an autosomal recessive connective tissue disorder characterized by congenital malformations (specific craniofacial features, and congenital multiple contractures) and progressive fragility-related complications (skin hyperextensibility, bruisability, and fragility with atrophic scars; recurrent dislocations; progressive talipes or spinal deformities; and large subcutaneous hematomas). In an attempt to develop a diagnostic screening method for this type of EDS, the amount of DS in the urine of patients was analyzed. Urinary DS was quantified by an anion-exchange chromatography after treatment with DS-specific degrading enzyme. DS was not detected in the urine of patients with homo- or compound heterozygous mutations in CHST14. These results suggest that the quantification of DS in urine is applicable to an initial diagnosis of DS-defective EDS. This is the first study to perform a urinary disaccharide compositional analysis of chondroitin sulfate (CS)/DS chains in patients with EDS caused by a CHST14/D4ST1 deficiency, and demonstrated the absence of DS chains. This result suggests systemic DS depletion in this disorder, and also proposes the usefulness of a urinary disaccharide compositional analysis of CS/DS chains as a non-invasive screening method for this disorder. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  18. (232)Th(d,4n)(230)Pa cross-section measurements at ARRONAX facility for the production of (230)U.

    Science.gov (United States)

    Duchemin, C; Guertin, A; Haddad, F; Michel, N; Métivier, V

    2014-05-01

    (226)Th (T1/2=31 min) is a promising therapeutic radionuclide since results, published in 2009, showed that it induces leukemia cells death and activates apoptosis pathways with higher efficiencies than (213)Bi. (226)Th can be obtained via the (230)U α decay. This study focuses on the (230)U production using the (232)Th(d,4n)(230)Pa(β-)(230)U reaction. Experimental cross sections for deuteron-induced reactions on (232)Th were measured from 30 down to 19 MeV using the stacked-foil technique with beams provided by the ARRONAX cyclotron. After irradiation, all foils (targets as well as monitors) were measured using a high-purity germanium detector. Our new (230)Pa cross-section values, as well as those of (232)Pa and (233)Pa contaminants created during the irradiation, were compared with previous measurements and with results given by the TALYS code. Experimentally, same trends were observed with slight differences in orders of magnitude mainly due to the nuclear data change. Improvements are ongoing about the TALYS code to better reproduce the data for deuteron-induced reactions on (232)Th. Using our cross-section data points from the (232)Th(d,4n)(230)Pa reaction, we have calculated the thick-target yield of (230)U, in Bq/μA·h. This value allows now to a full comparison between the different production routes, showing that the proton routes must be preferred. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Changing utilization of Stavudine (d4T) in HIV-positive people in 2006-2013 in the EuroSIDA study

    DEFF Research Database (Denmark)

    Podlekareva, Daria; Grint, D; Karpov, I

    2015-01-01

    OBJECTIVES: The long-term side effects of stavudine (d4T) led to recommendations in 2009 to phase out use of this drug. We aimed to describe temporal patterns of d4T use across Europe. METHODS: Patients taking combination antiretroviral therapy (cART) in EuroSIDA with follow-up after 1 January 2006...

  20. 17 CFR 240.19d-4 - Notice by the Public Company Accounting Oversight Board of disapproval of registration or of...

    Science.gov (United States)

    2010-04-01

    ... Accounting Oversight Board of disapproval of registration or of disciplinary action. (a) Definitions—(1... Accounting Oversight Board of disapproval of registration or of disciplinary action. 240.19d-4 Section 240.19d-4 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES...

  1. Extension of the analysis of the 3d4-3d34p transition array in Ni VII

    International Nuclear Information System (INIS)

    Hof, G.J. van het; Raassen, A.J.J.; Uylings, P.H.M.; Podobedova, L.I.; Ryabtsev, A.N.

    1989-01-01

    The spectrum of Ni VII has been photographed in the 190-265 A region using grazing incidence vacuum spectrographs. More than 400 lines have been classified. In the 3d 4 -configuration 32 of the 34 possible levels and in the 3d 3 4p-configuration 93 of the 110 levels are established. The lines and levels which have already been published are confirmed. The configurations are described both with the conventional Slater-Condon parameters and the recently developed orthogonal parameter set. The conventional set yields a standard deviation for the levels in the 3d 4 configuration of 46 cm -1 and of 163 cm -1 for the levels in the 3d 3 4p configuration. With the orthogonal set this decreases to 3.5 cm -1 and 130 cm -1 respectively. As a consequence of the perturbation by the inner shell excited 3p 5 3d 5 configuration the levels of the 3d 3 ( 2 F) 4p 3 F term show an average deviation of approx. -1400 cm -1 from their calculated values. The other levels can be described very well without taking this perturbation into account. (orig.)

  2. Visuospatial performance on an internet line judgment task and potential hormonal markers: sex, sexual orientation, and 2D:4D.

    Science.gov (United States)

    Collaer, Marcia L; Reimers, Stian; Manning, John T

    2007-04-01

    We investigated whether performance on a visuospatial line judgment task, the Judgment of Line Angle and Position-15 test (JLAP-15), showed evidence of sensitivity to early sex steroid exposure by examining how it related to sex, as well as to sexual orientation and 2D:4D digit ratios. Participants were drawn from a large Internet study with over 250,000 participants. In the main sample (ages 12-58 years), males outperformed females on the JLAP-15, showing a moderate effect size for sex. In agreement with a prenatal sex hormone hypothesis, line judgment accuracy in adults related to 2D:4D and sexual orientation, both of which are postulated to be influenced by early steroids. In both sexes, better visuospatial performance was associated with lower (more male-typical) digit ratios. For men, heterosexual participants outperformed homosexual/bisexual participants on the JLAP-15 and, for women, homosexual/bisexual participants outperformed heterosexual participants. In children aged 8-10 years, presumed to be a largely prepubertal group, boys also outperformed girls. These findings are consistent with the hypothesis that visuospatial ability is influenced by early sex steroids, although they do not rule out alternative explanations or additional influences. More broadly, such results support a prenatal sex hormone hypothesis that degree of androgen exposure may influence the neural circuitry underlying cognition (visuospatial ability) and sexual orientation as well as aspects of somatic (digit ratio) development.

  3. Environmental Dependence of Artifact CD Peaks of Chiral Schiff Base 3d-4f Complexes in Soft Mater PMMA Matrix

    Directory of Open Access Journals (Sweden)

    Yu Okamoto

    2011-10-01

    Full Text Available Four chiral Schiff base binuclear 3d-4f complexes (NdNi, NdCu, GdNi, and GdCu have been prepared and characterized by means of electronic and CD spectra, IR spectra, magnetic measurements, and X-ray crystallography (NdNi. A so-called artifact peak of solid state CD spectra, which was characteristic of oriented molecules without free molecular rotation, appeared at about 470 nm. Magnetic data of the complexes in the solid state (powder and in PMMA cast films or solutions indicated that only GdCu preserved molecular structures in various matrixes of soft maters. For the first time, we have used the changes of intensity of artifact CD peaks to detect properties of environmental (media solid state (KBr pellets, PMMA cast films, concentration dependence of PMMA in acetone solutions, and pure acetone solution for chiral 3d-4f complexes (GdCu. Rigid matrix keeping anisotropic orientation exhibited a decrease in the intensity of the artifact CD peak toward negative values. The present results suggest that solid state artifact CD peaks can be affected by environmental viscosity of a soft mater matrix.

  4. IM-16: A new microporous germanosilicate with a novel framework topology containing d4r and mtw composite building units

    International Nuclear Information System (INIS)

    Lorgouilloux, Yannick; Dodin, Mathias; Paillaud, Jean-Louis; Caullet, Philippe; Michelin, Laure; Josien, Ludovic; Ersen, Ovidiu; Bats, Nicolas

    2009-01-01

    The synthesis and the structure of IM-16 a new germanosilicate with a novel zeolitic topology prepared hydrothermally with the ionic liquid 3-ethyl-1-methyl-3H-imidazol-1-ium as the organic structure-directing agent are reported. The structure of calcined and partially rehydrated IM-16 of chemical formula |(H 2 O) 0.16 |[Si 3.47 Ge 2.53 O 12 ] was solved from powder XRD data in space group Cmcm with a=15.0861(2) A, b=17.7719(3) A, c=19.9764(3) A, V=5355.84(12) A 3 (Z=16). This new zeolite framework type contains 10-MRs channels and may be described from the d4r and mtw composite building units. - Graphical abstract: The synthesis and the structure of IM-16 a new germanosilicate with a novel zeolitic topology prepared hydrothermally with the ionic liquid 3-ethyl-1-methyl-3H-imidazol-1-ium as the organic structure-directing agent are reported. This new zeolite framework type contains 10-MRs channels and may be described from the d4r and mtw composite building units

  5. Corticosteroid receptors adopt distinct cyclical transcriptional signatures.

    Science.gov (United States)

    Le Billan, Florian; Amazit, Larbi; Bleakley, Kevin; Xue, Qiong-Yao; Pussard, Eric; Lhadj, Christophe; Kolkhof, Peter; Viengchareun, Say; Fagart, Jérôme; Lombès, Marc

    2018-05-07

    Mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) are two closely related hormone-activated transcription factors that regulate major pathophysiologic functions. High homology between these receptors accounts for the crossbinding of their corresponding ligands, MR being activated by both aldosterone and cortisol and GR essentially activated by cortisol. Their coexpression and ability to bind similar DNA motifs highlight the need to investigate their respective contributions to overall corticosteroid signaling. Here, we decipher the transcriptional regulatory mechanisms that underlie selective effects of MRs and GRs on shared genomic targets in a human renal cellular model. Kinetic, serial, and sequential chromatin immunoprecipitation approaches were performed on the period circadian protein 1 ( PER1) target gene, providing evidence that both receptors dynamically and cyclically interact at the same target promoter in a specific and distinct transcriptional signature. During this process, both receptors regulate PER1 gene by binding as homo- or heterodimers to the same promoter region. Our results suggest a novel level of MR-GR target gene regulation, which should be considered for a better and integrated understanding of corticosteroid-related pathophysiology.-Le Billan, F., Amazit, L., Bleakley, K., Xue, Q.-Y., Pussard, E., Lhadj, C., Kolkhof, P., Viengchareun, S., Fagart, J., Lombès, M. Corticosteroid receptors adopt distinct cyclical transcriptional signatures.

  6. A distinction of two discourses concerning wellbeing

    DEFF Research Database (Denmark)

    Wistoft, Karen; Qvortrup, Lars

    2017-01-01

    and behavioral mental health interventions, while the latter defines wellbeing in positive terms with a focus on wellbeing as the result of learning and with pedagogical interventions that only indirectly can support the individual’s learning activity. The former sees wellbeing as the result of a “wellbeing cure......The article concerns the current discourses concerning well-being with the point that it is important to make a distinction between a healthcare oriented discourse and a learning oriented discourse. The former defines wellbeing in negative terms and looks at causally oriented aspects of wellbeing......”, while the latter sees wellbeing as the result of wellbeing learning processes....

  7. Sex differences in college students' free drawings and their relationship to 2D:4D ratio and recalled childhood play behavior.

    Science.gov (United States)

    Rothkopf, Ian; Turgeon, Sarah M

    2014-02-01

    In a prior study, we observed that female-typical characteristics in elementary school girls' drawings were correlated with a feminized digit ratio (2D:4D), a marker for prenatal androgen exposure. However, this observation was limited to older girls, suggesting that social factors mediate the relationship between 2D:4D and drawing. To examine the hypothesis that the influence of prenatal androgen on girls' drawing is mediated by an effect of early androgens on sex-typical behavior, we examined 2D:4D, free drawings, and scores on the Recalled Childhood Gender Identity (RCGI) Questionnaire in a population of college students. Characteristics of participants' free drawings were assessed and those that showed sex differences were compared with 2D:4D and RCGI scores. Men had smaller 2D:4D ratios than women, used fewer total colors, used fewer pinks, purples, and blues, and had higher gender-typical scores on the RCGI. Women's drawings were more likely to contain flowers and animals and men's drawings were more likely to represent sports. Within-sex RCGI and 2D:4D scores were not significantly correlated. Significant within-sex relationships between 2D:4D and RCGI and drawing behavior were observed but the effects appeared to be independent; the hypothesis that gender-typical childhood behavior mediates the effect of prenatal androgen on drawing characteristics was not supported.

  8. Is sports choice and participation related to 2D:4D? A study among adult male students in Wrocław, Poland.

    Science.gov (United States)

    Koziel, Slawomir; Kociuba, Marek; Ignasiak, Zofia; Chakraborty, Raja

    2016-06-01

    Psychology and personality of individuals may have implications for choice of, and performance in sports disciplines. Individual- and group sports differ in psychological requirements, such as, competitiveness, sensation seeking and risk taking attitude, often required in sports. There is sex difference in human in these qualities, which also show association with prenatal testosterone exposures. Second-to-fourth digit lengths ratio (2D:4D) is an indicator of prenatal testosterone exposure. Lower 2D:4D indicates higher prenatal testosteron exposure and vice versa. Males generally have lower 2D:4D than females. This study cross-sectional study investigated the relationship of 2D:4D with team based- or individual sports. The participants were 421 Polish male students with a mean (+SD) age of 19.78 (+0.79) years. Among them, 139 were engaged in sports and 282 were not. Mean 2D:4D in each hand of individual sporting group was significantly lower than the team sports- and no sports groups. Participants not involved in any sports had the highest mean 2D:4D value. However, the team sportsmen’s 2D:4D did not differ from the non sporting group. Prenatal testosterone exposure might have implication in sports choice and participation.

  9. The dopamine D4 receptor gene (DRD4) moderates cultural difference in independent versus interdependent social orientation.

    Science.gov (United States)

    Kitayama, Shinobu; King, Anthony; Yoon, Carolyn; Tompson, Steve; Huff, Sarah; Liberzon, Israel

    2014-06-01

    Prior research suggests that cultural groups vary on an overarching dimension of independent versus interdependent social orientation, with European Americans being more independent, or less interdependent, than Asians. Drawing on recent evidence suggesting that the dopamine D4 receptor gene (DRD4) plays a role in modulating cultural learning, we predicted that carriers of DRD4 polymorphisms linked to increased dopamine signaling (7- or 2-repeat alleles) would show higher levels of culturally dominant social orientations, compared with noncarriers. European Americans and Asian-born Asians (total N = 398) reported their social orientation on multiple scales. They were also genotyped for DRD4. As in earlier work, European Americans were more independent, and Asian-born Asians more interdependent. This cultural difference was significantly more pronounced for carriers of the 7- or 2-repeat alleles than for noncarriers. Indeed, no cultural difference was apparent among the noncarriers. Implications for potential coevolution of genes and culture are discussed. © The Author(s) 2014.

  10. Does the index-to-ring finger length ratio (2D:4D) differ in amyotrophic lateral sclerosis (ALS)? Results from an international online case-control study.

    Science.gov (United States)

    Parkin Kullmann, Jane Alana; Pamphlett, Roger

    2017-08-07

    The ratio of the length of the index finger (2D) to the ring finger (4D) (2D:4D) has been reported to be lower (ie, 2Dcontrols. This has led to suggestions that exposure to increased prenatal testosterone, which also lowers this ratio, could be a risk factor for ALS. In an attempt to test this hypothesis, we examined 2D:4Ds from large numbers of patients with ALS and controls. An online multilingual questionnaire enabling respondents to measure their own index and ring finger lengths. Of the initial 949 respondents, 572 remained for analysis after elimination for inability to straighten fingers, not answering the question, statistical outliers and aged controls (112 males, 258 females). Unpaired t-tests with 95% CIs were used to assess differences in mean 2D:4Ds. Males had significantly lower mean 2D:4Ds than females, in both ALS and control groups, for both left and right hands. No significant differences were found in 2D:4Ds between ALS and control groups, in either males or females, for either left or right hands. Receiver operating characteristic curves showed no power for 2D:4Ds to predict ALS status in either males or females. 2D:4Ds did not differ between patients with ALS and controls in this study. This was despite the dataset being large enough to confirm the established finding of lower 2D:4Ds in males compared with females. These findings do not support the hypothesis that exposure to increased prenatal testosterone is a risk factor for ALS. A putative lower 2D:4D has been proposed to explain the link between ALS and exercise, but our results indicate that other exercise-related factors are more likely to explain this association. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. The relationship between second-to-fourth digit (2D:4D) ratios and problematic and pathological Internet use among Turkish university students.

    Science.gov (United States)

    Canan, Fatih; Karaca, Servet; Düzgün, Melike; Erdem, Ayşe Merve; Karaçaylı, Esranur; Topan, Nur Begüm; Lee, Sang-Kyu; Zhai, Zu Wei; Kuloğlu, Murat; Potenza, Marc N

    2017-03-01

    Background and aims The ratio of the second and fourth fingers (2D:4D ratio) is a sexually dimorphic trait, with men tending to have lower values than women. This ratio has been related to prenatal testosterone concentrations and addictive behaviors including problematic video-gaming. We aimed to investigate the possible association between 2D:4D ratios and Internet addiction and whether such a relationship would be independent of impulsivity. Methods A total of 652 university students (369 women, 283 men), aged 17-27 years, were enrolled in the study. Problematic and pathological Internet use (PPIU) was assessed using the Internet Addiction Test (IAT). The participants also completed the Barratt Impulsiveness Scale (version 11; BIS-11) and had their 2D:4D ratios measured. Results 2D:4D ratios were not significantly different in women with PPIU and in those with adaptive Internet use (AIU). Men with PPIU exhibited lower 2D:4D ratios on both hands when compared with those with AIU. Correlation analysis revealed that 2D:4D ratios on both hands were negatively correlated with IAT scores among men, but not among women. The multiple linear regression analysis revealed that age, duration of weekly Internet use, impulsiveness, and 2D:4D ratios on the right hand were independently associated with IAT scores among men, and impulsivity did not mediate the relationship between 2D:4D ratios and PPIU. Conclusions For men, 2D:4D ratios on the right hand were inversely correlated with Internet addiction severity even after controlling for individual differences in impulsivity. These findings suggest that high prenatal testosterone levels may contribute to the occurrence of PPIU among men.

  12. The new 3.5L V6 gasoline engine adopting the innovative stoichiometric direct injection system D-4S; Der neue 3.5L V6 Benzinmotor mit dem innovativen stoechiometrischen Direkteinspritzsystem D-4S

    Energy Technology Data Exchange (ETDEWEB)

    Tsuji, N.; Sugiyama, M.; Abe, S. [Toyota Motor Corp. (Japan)

    2006-07-01

    A new 3.5L V6 engine was introduced for the new Lexus sedan vehicles, GS350 and IS350 in Japan in August 2005. In 2006, this engine will be adapted to the power source of the new hybrid rear wheel driven vehicle GS450h. This new engine uses a newly developed stoichiometric direct injection system with two fuel injectors in each cylinder (this system is called D-4S: direct injection 4-stroke gasoline engine system superior version). One is a direct injection injector generating a dual-vertical-fan-shaped spray with wide dispersion, while the other is a port injector. This new fuel injection system can maximize the DI advantage for full-load performance. Simultaneously the optimisation of the intake and exhaust system and the increase of stiffness of the moving parts such as the timing chain system and the valve train system enable a specific power of 67kW/L and 234kW at 6400r/min to be achieved, placing it near the top of all naturally aspirated production gasoline engines in the world. Additionally, employing the dual-VVTi system (intake and exhaust VVT system) and the long dual exhaust pipe, an excellent maximum torque of 380Nm at 4800r/min was achieved while keeping 90 percent of maximum torque for a wide engine speed range from 2000r/min to 6500r/min. (orig.)

  13. The 2D:4D ratio and its relationship with other androgenisation parameters in parents of individuals with autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Ángel Romero-Martínez

    2013-01-01

    Full Text Available The 2D:4D ratio is the quotient between the index and ring finger lengths and is a non-direct indicator of androgenisation. If prenatal testosterone levels in the amniotic fluid are high then the probability increases of developing lower ratio values. It has been suggested that people with autism spectrum disorders (ASD and their parents may have highly androgenised brains, and for this reason the 2D:4D ratio is used as a marker of such idiosyncrasies. This study aims to analyse if parents of people with ASD differ from the general population in several parameters of androgenisation related to the 2D:4D ratio. The sample was composed of 43 parents of offspring with ASD and 42 controls who had the 2D:4D ratio measured, answered several trait questionnaires, and had their testosterone and cortisol levels measured. Although there were no differences between groups in the 2D:4D ratio, the left hand of the ASD parents showed greater predictive ability to explain empathy and autism quotients, cooperative behaviour, and cortisol levels. In addition, the severity of the symptoms of their offspring was predicted only with male parents. The results indicate that the 2D:4D ratio could be used together with other parameters as an indicator of the likelihood of developing autistic traits in offspring.

  14. Dopamine receptor gene d4 polymorphisms and early sexual onset: gender and environmental moderation in a sample of african-american youth.

    Science.gov (United States)

    Kogan, Steven M; Lei, Man-Kit; Beach, Steven R H; Brody, Gene H; Windle, Michael; Lee, Sunbok; MacKillop, James; Chen, Yi-Fu

    2014-08-01

    Early sexual onset and its consequences disproportionately affect African-American youth, particularly male youth. The dopamine receptor D4 gene (DRD4) has been linked to sexual activity and other forms of appetitive behavior, particularly for male youth and in combination with environmental factors (gene × environment [G × E] effects). The differential susceptibility perspective suggests that DRD4 may exert this effect by amplifying the effects of both positive and negative environments. We hypothesized that DRD4 status would amplify the influence of both positive and negative neighborhood environments on early sexual onset among male, but not female, African-Americans. Hypotheses were tested with self-report, biospecimen, and census data from five prospective studies of male and female African-American youth in rural Georgia communities, N = 1,677. Early sexual onset was defined as intercourse before age 14. No significant G × E findings emerged for female youth. Male youth with a DRD4 long allele were more likely than those with two DRD4 short alleles to report early sexual onset in negative community environments and not to report early onset in positive community environments. Dopaminergic regulation of adolescent sexual behaviors may operate differently by gender. DRD4 operated as an environmental amplification rather than a vulnerability factor. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  15. Adaptive antenna system by ESP32-PICO-D4 and its application to web radio system

    Directory of Open Access Journals (Sweden)

    Toshiro Kodera

    2018-04-01

    Full Text Available Adaptive antenna technique has an important role in the IoT environment in order to establish reliable and stable wireless communication in high congestion situation. Even if knowing antenna characteristics in advance, electromagnetic wave propagation in non-line-of-sight environment is very complex and unpredictable, therefore, the adjustment the antenna radiation for the optimum signal reception is important for the better wireless link. This article presents a simple but effective adaptive antenna system for Wi-Fi utilizing the function of a highly integrated component, ESP32-PICO-D4. This chip is a system-in-chip containing all components for Wi-Fi and Bluetooth application except for antenna. Together with SP3T RF switch and dielectric antennas and high-resolution audio DAC, completed web-radio system is made in the size of 50 × 50 mm. Keywords: Beam switching, Adaptive antenna, System-in-chip, ESP32, Web-radio

  16. 3s--3p, 3p--3d, and 3d--4f transitions of sodiumlike ions

    International Nuclear Information System (INIS)

    Reader, J.; Kaufman, V.; Sugar, J.; Olof Ekberg, J.; Feldman, U.; Brown, C.M.; Seely, J.F.; Rowan, W.L.

    1987-01-01

    New measurements have been made for wavelengths of the 3s--3p, 3p--3d, and 3d--4f transitions of the sodiumlike ions Cu/sup 18+/, Zn/sup 19+/, Ga/sup 20+/, Ge/sup 21+/, As/sup 22+/, Se/sup 23+/, Br/sup 24+/, Kr/sup 25+/, Y/sup 28+/, Zr/sup 29+/, Nb/sup 30+/, Mo/sup 31+/, Ru/sup 33+/, Rh/sup 34+/, Pd/sup 35+/, Ag/sup 36+/, and Sn/sup 39+/. The measurements were made by photographing laser-produced plasmas and tokamak plasmas with grazing-incidence spectrographs. The energies of the transitions were also calculated with Dirac--Fock computer codes. By fitting the differences between the observed and calculated wave numbers to simple formulas, least-squares-fitted wavelengths for all sodiumlike ions from Ar 7+ to Xe/sup 43+/ were determined. The estimated uncertainty of the fitted wavelengths is +- 0.007 A, which makes them useful as reference values. The wavelengths range from 9 to 713 A

  17. Dopamine D4 Receptor Gene Polymorphism in a Sample of Egyptian Children With Attention-Deficit Hyperactivity Disorder (ADHD).

    Science.gov (United States)

    ElBaz Mohamed, Farida; Kamal, Tarek Mostafa; Zahra, Sally Soliman; Khfagy, Mona Abdel Hakiem; Youssef, Azza Mohamed

    2017-02-01

    This study aimed to detect DRD4 receptor gene polymorphisms in attention-deficit hyperactivity disorder (ADHD) children and to correlate their phenotype-genotype. Fifty children with ADHD were diagnosed by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria and were subjected to Conners Parent Rating Scale. All cases and controls were subjected to history taking, physical examination, IQ assessment, and dopamine receptor D4 (DRD4) exon 3 genotyping. The 7-repeat allele was present only in controls, whereas 2-repeat allele was present in the ADHD children (heterozygous 2-repeat allele in 16% and homozygous in 26% of cases). Eight percent of cases had homozygous 4-repeat allele vs 28% of controls, whereas 10% of cases had heterozygous 4-repeat allele vs 6% of controls, with its predominance in controls. The 2-repeat and 4-repeat alleles have been associated with more inattention, hyperactivity, and impulsivity phenotypes. In conclusion, children with ADHD had a significant presence of the 2-repeat allele and absence of the 7-repeat allele.

  18. Finger length ratio (2D:4D) correlates with physical aggression in men but not in women.

    Science.gov (United States)

    Bailey, Allison A; Hurd, Peter L

    2005-03-01

    Finger length ratio (2D:4D) is a sexually dimorphic trait. Men have relatively shorter second digits (index fingers) than fourth digits (ring fingers). Smaller, more masculine, digit ratios are thought to be associated with either higher prenatal testosterone levels or greater sensitivity to androgens, or both. Men with more masculine finger ratios are perceived as being more masculine and dominant by female observers, and tend to perform better in a number of physical sports. We hypothesized that digit ratio would correlate with propensity to engage in aggressive behavior. We examined the relationship between trait aggression, assayed using a questionnaire, and finger length ratio in both men and women. Men with lower, more masculine, finger length ratios had higher trait physical aggression scores (r(partial) = -0.21, N = 134, P = 0.028). We found no correlation between finger length ratio and any form of aggression in females. These results are consistent with the hypothesis that testosterone has an organizational effect on adult physical aggression in men.

  19. Energy spectra analysis of the four-layer DOI detector for the brain PET scanner: jPET-D4

    International Nuclear Information System (INIS)

    Yoshida, Eiji; Kitamura, Keishi; Tsuda, Tomoaki; Shibuya, Kengo; Yamaya, Taiga; Inadama, Naoko; Hasegawa, Tomoyuki; Murayama, Hideo

    2006-01-01

    A depth of interaction (DOI) detector is being developed for the brain PET scanner, jPET-D4. We introduce a light output correction procedure to compensate for variations among the crystal elements in the DOI detector. Under uniform irradiation with 511 keV gamma rays, we estimate the light output of each crystal element by identifying each crystal element, and generate a look-up table (LUT) for light output correction. We evaluate the energy resolution of all crystal elements. The energy resolution of 16% is achieved after light output correction for all crystal elements. The DOI detector can correct light output variations that are related to the DOI. We analyze the crystal position dependence of the energy spectra due to inter-crystal scattering among the multiple crystal elements in the DOI detector. It is highly possible that gamma rays interacting with central crystal elements in the crystal array are absorbed by surrounding crystal elements and the Compton part of the energy spectrum is decreased. Inter-crystal scattering has less impact on the energy resolution of the DOI detector

  20. 1-[3-(4-Butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1) as a Model for the Rational Design of a Novel Class of Brain Penetrant Ligands with High Affinity and Selectivity for Dopamine D4 Receptor.

    Science.gov (United States)

    Del Bello, Fabio; Bonifazi, Alessandro; Giorgioni, Gianfabio; Cifani, Carlo; Micioni Di Bonaventura, Maria Vittoria; Petrelli, Riccardo; Piergentili, Alessandro; Fontana, Stefano; Mammoli, Valerio; Yano, Hideaki; Matucci, Rosanna; Vistoli, Giulio; Quaglia, Wilma

    2018-04-26

    In the present article, the M 1 mAChR bitopic agonist 1-[3-(4-butylpiperidin-1-yl)propyl]-1,2,3,4-tetrahydroquinolin-2-one (77-LH-28-1, 1) has been demonstrated to show unexpected D 4 R selectivity over D 2 R and D 3 R and to behave as a D 4 R antagonist. To better understand the structural features required for the selective interaction with the D 4 R and to obtain compounds unable to activate mAChRs, the aliphatic butyl chain and the piperidine nucleus of 1 were modified, affording compounds 2-14. The 4-benzylpiperidine 9 and the 4-phenylpiperazine 12 showed high D 4 R affinity and selectivity not only over the other D 2 -like subtypes, but also over M 1 -M 5 mAChRs. Derivative 12 was also highly selective over some selected off-targets. This compound showed biased behavior, potently and partially activating G i protein and inhibiting β-arrestin2 recruitment in functional studies. Pharmacokinetic studies demonstrated that it was characterized by a relevant brain penetration. Therefore, 12 might be a useful tool to better clarify the role played by D 4 R in disorders in which this subtype is involved.

  1. Toward Precision Medicine: TBC1D4 Disruption Is Common Among the Inuit and Leads to Underdiagnosis of Type 2 Diabetes.

    Science.gov (United States)

    Manousaki, Despoina; Kent, Jack W; Haack, Karin; Zhou, Sirui; Xie, Pingxing; Greenwood, Celia M; Brassard, Paul; Newman, Deborah E; Cole, Shelley; Umans, Jason G; Rouleau, Guy; Comuzzie, Anthony G; Richards, J Brent

    2016-11-01

    A common nonsense mutation in TBC1D4 was recently found to substantially increase the odds of type 2 diabetes in Greenlandic Inuit, leading to exclusively increased postprandial glucose. We investigated the frequency and effect of the TBC1D4 mutation on glucose metabolism and type 2 diabetes diagnosis among Canadian and Alaskan Inuit. Exome sequencing of the TBC1D4 variant was performed in 114 Inuit from Nunavik, Canada, and Sanger sequencing was undertaken in 1,027 Alaskan Inuit from the Genetics of Coronary Artery Disease in Alaskan Natives (GOCADAN) Study. Association testing evaluated the effect of the TBC1D4 variant on diabetes-related metabolic traits and diagnosis. The TBC1D4 mutation was present in 27% of Canadian and Alaskan Inuit. It was strongly associated with higher glucose (effect size +3.3 mmol/L; P = 2.5 x 10 -6 ) and insulin (effect size +175 pmol/L; P = 0.04) 2 h after an oral glucose load in homozygote carriers. TBC1D4 carriers with prediabetes and type 2 diabetes had an increased risk of remaining undiagnosed unless postprandial glucose values were tested (odds ratio 5.4 [95% CI 2.5-12]) compared with noncarriers. Of carriers with prediabetes or type 2 diabetes, 32% would remain undiagnosed without an oral glucose tolerance test (OGTT). Disruption of TBC1D4 is common among North American Inuit, resulting in exclusively elevated postprandial glucose. This leads to underdiagnosis of type 2 diabetes, unless an OGTT is performed. Accounting for genetic factors in the care of Inuit with diabetes provides an opportunity to implement precision medicine in this population. © 2016 by the American Diabetes Association.

  2. The left hand second to fourth digit ratio (2D:4D is not related to any physical fitness component in adolescent girls.

    Directory of Open Access Journals (Sweden)

    Maarten W Peeters

    Full Text Available INTRODUCTION: The second to fourth-digit-ratio (2D:4D, a putative marker of prenatal androgen action and a sexually dimorphic trait, has been suggested to be related with fitness and sports performance, although results are not univocal. Most studies however focus on a single aspect of physical fitness or one sports discipline. METHODS: In this study the 2D:4D ratio of 178 adolescent girls (age 13.5-18 y was measured on X-rays of the left hand. The relation between 2D:4D digit ratio and multiple aspects of physical fitness (balance, speed of limb movement, flexibility, explosive strength, static strength, trunk strength, functional strength, running speed/agility, and endurance was studied by correlation analyses and stepwise multiple regression. For comparison the relation between these physical fitness components and a selected number of objectively measured anthropometric traits (stature, mass, BMI, somatotype components and the Bayer & Bailey androgyny index are presented alongside the results of 2D:4D digit ratio. RESULTS: Left hand 2D:4D digit ratio (0.925±0.019 was not significantly correlated with any of the physical fitness components nor any of the anthropometric variables included in the present study. 2D:4D did not enter the multiple stepwise regression for any of the physical fitness components in which other anthropometric traits explained between 9.2% (flexibility and 33.9% (static strength of variance. CONCLUSION: Unlike other anthropometric traits the 2D:4D digit ratio does not seem to be related to any physical fitness component in adolescent girls and therefore most likely should not be considered in talent detection programs for sporting ability in girls.

  3. The left hand second to fourth digit ratio (2D:4D) is not related to any physical fitness component in adolescent girls.

    Science.gov (United States)

    Peeters, Maarten W; Van Aken, Katrijn; Claessens, Albrecht L

    2013-01-01

    The second to fourth-digit-ratio (2D:4D), a putative marker of prenatal androgen action and a sexually dimorphic trait, has been suggested to be related with fitness and sports performance, although results are not univocal. Most studies however focus on a single aspect of physical fitness or one sports discipline. In this study the 2D:4D ratio of 178 adolescent girls (age 13.5-18 y) was measured on X-rays of the left hand. The relation between 2D:4D digit ratio and multiple aspects of physical fitness (balance, speed of limb movement, flexibility, explosive strength, static strength, trunk strength, functional strength, running speed/agility, and endurance) was studied by correlation analyses and stepwise multiple regression. For comparison the relation between these physical fitness components and a selected number of objectively measured anthropometric traits (stature, mass, BMI, somatotype components and the Bayer & Bailey androgyny index) are presented alongside the results of 2D:4D digit ratio. Left hand 2D:4D digit ratio (0.925±0.019) was not significantly correlated with any of the physical fitness components nor any of the anthropometric variables included in the present study. 2D:4D did not enter the multiple stepwise regression for any of the physical fitness components in which other anthropometric traits explained between 9.2% (flexibility) and 33.9% (static strength) of variance. Unlike other anthropometric traits the 2D:4D digit ratio does not seem to be related to any physical fitness component in adolescent girls and therefore most likely should not be considered in talent detection programs for sporting ability in girls.

  4. Dopamine D4 Receptor Gene Associated with the Frontal-Striatal-Cerebellar Loop in Children with ADHD: A Resting-State fMRI Study.

    Science.gov (United States)

    Qian, Andan; Wang, Xin; Liu, Huiru; Tao, Jiejie; Zhou, Jiejie; Ye, Qiong; Li, Jiance; Yang, Chuang; Cheng, Jingliang; Zhao, Ke; Wang, Meihao

    2018-03-21

    Attention deficit hyperactivity disorder (ADHD) is a common childhood neuropsychiatric disorder that has been linked to the dopaminergic system. This study aimed to investigate the effects of regulation of the dopamine D4 receptor (DRD4) on functional brain activity during the resting state in ADHD children using the methods of regional homogeneity (ReHo) and functional connectivity (FC). Resting-state functional magnetic resonance imaging data were analyzed in 49 children with ADHD. All participants were classified as either carriers of the DRD4 4-repeat/4-repeat (4R/4R) allele (n = 30) or the DRD4 2-repeat (2R) allele (n = 19). The results showed that participants with the DRD4 2R allele had decreased ReHo bilaterally in the posterior lobes of the cerebellum, while ReHo was increased in the left angular gyrus. Compared with participants carrying the DRD4 4R/4R allele, those with the DRD4 2R allele showed decreased FC to the left angular gyrus in the left striatum, right inferior frontal gyrus, and bilateral lobes of the cerebellum. The increased FC regions included the left superior frontal gyrus, medial frontal gyrus, and rectus gyrus. These data suggest that the DRD4 polymorphisms are associated with localized brain activity and specific functional connections, including abnormality in the frontal-striatal-cerebellar loop. Our study not only enhances the understanding of the correlation between the cerebellar lobes and ADHD, but also provides an imaging basis for explaining the neural mechanisms underlying ADHD in children.

  5. Future changes in summer mean and extreme precipitation frequency in Japan by d4PDF regional climate simulations

    Science.gov (United States)

    Okada, Y.; Ishii, M.; Endo, H.; Kawase, H.; Sasaki, H.; Takayabu, I.; Watanabe, S.; Fujita, M.; Sugimoto, S.; Kawazoe, S.

    2017-12-01

    Precipitation in summer plays a vital role in sustaining life across East Asia, but the heavy rain that is often generated during this period can also cause serious damage. Developing a better understanding of the features and occurrence frequency of this heavy rain is an important element of disaster prevention. We investigated future changes in summer mean and extreme precipitation frequency in Japan using large ensemble dataset which simulated by the Non-Hydrostatic Regional Climate Model with a horizontal resolution of 20km (NHRCM20). This dataset called database for Policy Decision making for Future climate changes (d4PDF), which is intended to be utilized for the impact assessment studies and adaptation planning to global warming. The future climate experiments assume the global mean surface air temperature rise 2K and 4K from the pre-industrial period. We investigated using this dataset future changes of precipitation in summer over the Japanese archipelago based on observational locations. For mean precipitation in the present-day climate, the bias of the rainfall for each month is within 25% even considering all members (30 members). The bias at each location is found to increase by over 50% on the Pacific Ocean side of eastern part of Japan and interior locations of western part of Japan. The result in western part of Japan depends on the effect of the elevations in this model. The future changes in mean precipitation show a contrast between northern and southern Japan, with the north showing a slight increase but the south a decrease. The future changes in the frequency of extreme precipitation in the national average of Japan increase at 2K and 4K simulations compared with the present-day climate, respectively. The authors were supported by the Social Implementation Program on Climate Change Adaptation Technology (SI-CAT), the Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Japan.

  6. Effect of dopamine receptor D4 (DRD4) haplotypes on general psychopathology in patients with eating disorders.

    Science.gov (United States)

    Gervasini, Guillermo; González, Luz M; Gamero-Villarroel, Carmen; Mota-Zamorano, Sonia; Carrillo, Juan Antonio; Flores, Isalud; García-Herráiz, Angustias

    2018-05-15

    Among the many candidate genes analyzed in eating disorder (ED) patients, those involved in dopaminergic functions may be of special relevance, as dopamine is known to play a significant role in feeding behavior, the distortion of body image, hyperactivity and reward and reinforcement processes. We aimed to determine the effect of functional polymorphisms and haplotypes in the Dopamine Receptor D4 (DRD4) gene on general psychopathological symptoms in ED patients. Two-hundred-and-seventy-three ED patients [199 with Anorexia Nervosa (AN) and 74 with Bulimia Nervosa (BN)] completed the SCL-90R inventory and were genotyped for four functional, clinically relevant DRD4 polymorphisms: three variants in the promoter region [120-bp tandem repeat (TR, long vs. short allele), C-616G and C-521 T] and a variable number of tandem repeats (VNTR) in exon 3 (7R vs. non-7R allele). After correcting for multiple testing, none of the assayed polymorphisms were individually associated with SCL-90R results. Four DRD4 haplotypes (*1-*4) were detected in the patients with a frequency > 0.1. In the BN group, haplotype *2 (non7R-TR long-C-C) was associated with higher scores in the three global SCL-90R indices (GSI, PSDI and PST) after Bonferroni correction (p ≤ 0.01 in all instances). Furthermore, carriers of this haplotype displayed higher scores (worst symptomatology) in Somatization, Obsessive-Compulsive, Anxiety, Phobic anxiety, Paranoid ideation and the test additional items (p-values for the differences between carriers vs. non-carriers ranging from 0.0001 to 0.0110). Certain combinations of DRD4 variants may contribute to psychopathological features in BN patients. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Fracto-mechanoluminescent light emission of EuD4TEA-PDMS composites subjected to high strain-rate compressive loading

    Science.gov (United States)

    Ryu, Donghyeon; Castaño, Nicolas; Bhakta, Raj; Kimberley, Jamie

    2017-08-01

    The objective of this study is to understand light emission characteristics of fracto-mechanoluminescent (FML) europium tetrakis(dibenzoylmethide)-triethylammonium (EuD4TEA) crystals under high strain-rate compressive loading. As a sensing material that can play a pivotal role for the self-powered impact sensor technology, it is important to understand transformative light emission characteristics of the FML EuD4TEA crystals under high strain-rate compressive loading. First, EuD4TEA crystals were synthesized and embedded into polydimethylsiloxane (PDMS) elastomer to fabricate EuD4TEA-PDMS composite test specimens. Second, the prepared EuD4TEA-PDMS composites were tested using the modified Kolsky bar setup equipped with a high-speed camera. Third, FML light emission was captured to yield 12 bit grayscale video footage, which was processed to quantify the FML light emission. Finally, quantitative parameters were generated by taking into account pixel values and population of pixels of the 12 bit grayscale images to represent FML light intensity. The FML light intensity was correlated with high strain-rate compressive strain and strain rate to understand the FML light emission characteristics under high strain-rate compressive loading that can result from impact occurrences.

  8. Anticancer properties of distinct antimalarial drug classes.

    Directory of Open Access Journals (Sweden)

    Rob Hooft van Huijsduijnen

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

  9. Anticancer Properties of Distinct Antimalarial Drug Classes

    Science.gov (United States)

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

    2013-01-01

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

  10. EarthServer - an FP7 project to enable the web delivery and analysis of 3D/4D models

    Science.gov (United States)

    Laxton, John; Sen, Marcus; Passmore, James

    2013-04-01

    EarthServer aims at open access and ad-hoc analytics on big Earth Science data, based on the OGC geoservice standards Web Coverage Service (WCS) and Web Coverage Processing Service (WCPS). The WCS model defines "coverages" as a unifying paradigm for multi-dimensional raster data, point clouds, meshes, etc., thereby addressing a wide range of Earth Science data including 3D/4D models. WCPS allows declarative SQL-style queries on coverages. The project is developing a pilot implementing these standards, and will also investigate the use of GeoSciML to describe coverages. Integration of WCPS with XQuery will in turn allow coverages to be queried in combination with their metadata and GeoSciML description. The unified service will support navigation, extraction, aggregation, and ad-hoc analysis on coverage data from SQL. Clients will range from mobile devices to high-end immersive virtual reality, and will enable 3D model visualisation using web browser technology coupled with developing web standards. EarthServer is establishing open-source client and server technology intended to be scalable to Petabyte/Exabyte volumes, based on distributed processing, supercomputing, and cloud virtualization. Implementation will be based on the existing rasdaman server technology developed. Services using rasdaman technology are being installed serving the atmospheric, oceanographic, geological, cryospheric, planetary and general earth observation communities. The geology service (http://earthserver.bgs.ac.uk/) is being provided by BGS and at present includes satellite imagery, superficial thickness data, onshore DTMs and 3D models for the Glasgow area. It is intended to extend the data sets available to include 3D voxel models. Use of the WCPS standard allows queries to be constructed against single or multiple coverages. For example on a single coverage data for a particular area can be selected or data with a particular range of pixel values. Queries on multiple surfaces can be

  11. Finger Length Ratio (2D:4D) in Central India and an Attempt to Verify Fraternal Birth Order Effect: A Population Based Cross-Sectional Study.

    Science.gov (United States)

    Maitra, Arjun; Maitra, Chaitali; Jha, Dilip Kumar; Biswas, Rakesh

    2016-12-01

    A normal physiology of a human being is not mere a series of functions occurring with specific intensities and timing. There are lot of factors that may change the normal physiological activity within normal limits. Finger length ratio is one of the markers of intrauterine androgen exposure and it is debated and contradicted by many authors. Digit ratio varies among the ethnicities. Many Indian studies show that there is considerable difference in finger length ratio in different population. Data regarding Central India was not found on extensive search. To find out the finger length ratio and explore the birth order effect on finger length ratio among the first two successive born in the said population. We conducted a survey on 1500 volunteer persons (800 male and 700 female) over two years of time. We measured the length of the index finger (2D) and ring finger (4D) of both the hands and asked about their birth order history to find out the digit ratio for Central India population and any existing correlation of the same with birth order. T Test and Analysis of Variance (ANOVA) were used for the measure of significance and difference among the groups. The peffect among the eldest, second born with elder brother and second born with elder sister groups, no significant (p>0.05) variation for finger length ratio of right and left hands observed in both male and female population. Our study reports that the finger length ratio (2D:4D) for Central India population did not show significant association between finger length ratio and fraternal birth order among the first two successive born.

  12. Synthesis of some (eta-arene)dihydridorhenium cations and their reactions with LiAlH4 and LiAlD4

    International Nuclear Information System (INIS)

    Baudrey, D.; Boydell, P.; Ephritikhine, M.

    1986-01-01

    A series of cations [Re(eta-arene)H 2 (PPh 3 ) 2 ] + (arene benzene, toluene, p-xylene, or mesitylene) was prepared from the corresponding neutral dihydridocyclohexadienyl complexes by treatment with CPh 3 BF 4 . These cations reacted with LiAlH 4 and LiAlD 4 to form dihydridocyclohexadienyl complexes. The unusual selectivity of the hydride attack is explained by steric interactions between the ring methyl groups and the bulky phosphine ligands. The initial product of the reaction of the eta-mesitylene cation with LiAlD 4 allows the isomerisation mechanism for the cyclohexadienyl complexes to be clarified. (author)

  13. Distinctive G Protein-Dependent Signaling by Protease-Activated Receptor 2 (PAR2 in Smooth Muscle: Feedback Inhibition of RhoA by cAMP-Independent PKA.

    Directory of Open Access Journals (Sweden)

    Wimolpak Sriwai

    Full Text Available We examined expression of protease-activated receptors 2 (PAR2 and characterized their signaling pathways in rabbit gastric muscle cells. The PAR2 activating peptide SLIGRL (PAR2-AP stimulated Gq, G13, Gi1, PI hydrolysis, and Rho kinase activity, and inhibited cAMP formation. Stimulation of PI hydrolysis was partly inhibited in cells expressing PAR2 siRNA, Gaq or Gai minigene and in cells treated with pertussis toxin, and augmented by expression of dominant negative regulator of G protein signaling (RGS4(N88S. Stimulation of Rho kinase activity was abolished by PAR-2 or Ga13 siRNA, and by Ga13 minigene. PAR2-AP induced a biphasic contraction; initial contraction was selectively blocked by the inhibitor of PI hydrolysis (U73122 or MLC kinase (ML-9, whereas sustained contraction was selectively blocked by the Rho kinase inhibitor (Y27632. PAR2-AP induced phosphorylation of MLC20, MYPT1 but not CPI-17. PAR2-AP also caused a decrease in the association of NF-kB and PKA catalytic subunit: the effect of PAR2-AP was blocked by PAR2 siRNA or phosphorylation-deficient RhoA (RhoA(S188A. PAR2-AP-induced degradation of IkBa and activation of NF-kB were abolished by the blockade of RhoA activity by Clostridium botulinum C3 exoenzyme suggesting RhoA-dependent activation of NF-kB. PAR2-AP-stimulated Rho kinase activity was significantly augmented by the inhibitors of PKA (myristoylated PKI, IKK2 (IKKIV or NF-kB (MG132, and in cells expressing dominant negative mutants of IKK (IKK(K44A, IkBa (IkBa (S32A/S36A or RhoA(S188A, suggesting feedback inhibition of Rho kinase activity via PKA derived from NF-kB pathway. PAR2-AP induced phosphorylation of RhoA and the phosphorylation was attenuated in cells expressing phosphorylation-deficient RhoA(S188A. Our results identified signaling pathways activated by PAR2 to mediate smooth muscle contraction and a novel pathway for feedback inhibition of PAR2-stimulated RhoA. The pathway involves activation of the NF-kB to

  14. Seven 3d-4f coordination polymers of macrocyclic oxamide with polycarboxylates: Syntheses, crystal structures and magnetic properties

    Energy Technology Data Exchange (ETDEWEB)

    Xin, Na [College of Chemistry, Tianjin Normal University, Tianjin 300387 (China); Key Laboratory of Inorganic-Organic Hybrid Functional Material Chemistry, Ministry of Education (China); Tianjin Key Laboratory of Structure and Performance for Functional Molecules (China); Sun, Ya-Qiu, E-mail: hxxysyq@mail.tjnu.edu.cn [College of Chemistry, Tianjin Normal University, Tianjin 300387 (China); Key Laboratory of Inorganic-Organic Hybrid Functional Material Chemistry, Ministry of Education (China); Tianjin Key Laboratory of Structure and Performance for Functional Molecules (China); Zheng, Yan-Feng; Xu, Yan-Yan; Gao, Dong-Zhao; Zhang, Guo-Ying [College of Chemistry, Tianjin Normal University, Tianjin 300387 (China); Key Laboratory of Inorganic-Organic Hybrid Functional Material Chemistry, Ministry of Education (China); Tianjin Key Laboratory of Structure and Performance for Functional Molecules (China)

    2016-11-15

    Seven new 3d–4f heterometallic coordination polymers, [Ln(CuL){sub 2}(Hbtca)(btca)(H{sub 2}O)]·2H{sub 2}O (Ln = Tb{sup III}1, Pr{sup III}2, Sm{sup III}3, Eu{sup III}4, Yb{sup III}5), [Nd(NiL)(nip)(Rnip)]·0·25H{sub 2}O·0.25CH{sub 3}OH (R= 0.6CH{sub 3}, 0.4H) 6 and [Nd{sub 2}(NiL)(nip){sub 3}(H{sub 2}O)]·2H{sub 2}O 7(CuL or NiL, H{sub 2}L = 2, 3-dioxo-5, 6, 14, 15-dibenzo-1, 4, 8, 12-tetraazacyclo-pentadeca-7, 13-dien; H{sub 2}btca = benzotriazole-5-carboxylic acid; H{sub 2}nip = 5-nitroisophthalic acid) have been synthesized by a solvothermal method and characterized by single-crystal X-ray diffraction. Complexes 1–5 exhibit a double-strand meso-helical chain structures formed by [Ln{sup III}Cu{sup II}{sub 2}] units via the oxamide and benzotriazole-5-carboxylate bridges, while complex 6 exhibits a four-strand meso-helical chain formed by NdNi unit via the oxamide and 5-nitroisophthalate bridges. Complex 7 consists of a 2D layer framework formed by four-strand meso-helical chain via the nip{sup 2−} bridges. Moreover, the magnetic properties of them were investigated, and the best-fit analysis of χ{sub M}T versus T show that the anisotropic contribution of Ln(III) ions (arising from the spin-orbit coupling or the crystal field perturbation) dominates (weak exchange limit) in these complexes(for 3, λ = 214.6 cm{sup −1}, zj’ = −0.33 cm{sup −1}, g{sub av} = 1.94; for 5, Δ = 6.98 cm{sup −1}, zj’ = 1.53 cm{sup −1}, g{sub av} = 1.85). - Graphical-abstract: Seven novel oxamido-bridged 3d-4f heterometallic coordination polymers with benzotriazole-5-carboxylate or 5-nitroisophthalate co-ligands under solvothermal reaction conditions. Polymers 1–7 hold 1D or 2D framework structure, viz., double-strand meso-helical chain of 1–5, four-strand meso-helical chain of 6, and 2D net of 7 consisting of four-strand meso-helical chain. Moreover, the temperature dependences of magnetic susceptibilities of compounds 1–7 were also studied.

  15. Investigation of a Putative Estrogen-Imprinting Gene, Phosphodiesterase Type IV Variant (Pde4d4), in Determining Prostate Cancer Risk

    Science.gov (United States)

    2008-04-01

    arrays. Methods Mol Biol 2002;200:87–100. [78] Craig JM, Kraus J, Cremer T. Removal of repetitive sequences from FISH probes using PCR-assisted affinity...Worcester, MA), David Hepps, MD, and Lynn Birch for technical contributions. Figure 5. Alterations in PDE4D4 CpG methylation and gene expression in NbE-1

  16. Implementation of Online Peer Assessment in a Design for Learning and Portfolio (D4L+P) Program to Help Students Complete Science Projects

    Science.gov (United States)

    Wuttisela, Karntarat; Wuttiprom, Sura; Phonchaiya, Sonthi; Saengsuwan, Sayant

    2016-01-01

    Peer assessment was one of the most effective strategies to improve students' understanding, metacognitive skills, and social interaction. An online tool, "Designing for Learning and Portfolio (D4L+P)", was developed solely to support the T5 (tasks, tools, tutorials, topicresources, and teamwork) method of teaching and learning. This…

  17. Maternal smoking during pregnancy and possible effects of in utero testosterone: evidence from the 2D:4D finger length ratio

    NARCIS (Netherlands)

    Rizwan, S.; Manning, J. T.; Brabin, B. J.

    2007-01-01

    OBJECTIVES: Maternal smoking during pregnancy is linked to high fetal testosterone (FT), and an increased risk in offspring for autism, ADHD, conduct disorder, antisocial behaviour and criminal outcomes. The ratio of the length of the 2nd and 4th fingers (2D:4D) is thought to be negatively related

  18. The presence of aggression cues inverts the relation between digit ratio (2D:4D) and pro-social behaviour in a dictator game

    NARCIS (Netherlands)

    Millet, K.; Dewitte, S.

    2009-01-01

    Digit ratio (2D:4D) is a sexually dimorphic trait. Men have relatively shorter index (2D) compared to ring (4D) fingers than women. More masculine ratios are thought to be influenced by higher prenatal testosterone levels. In the present paper, we aim to show the context-dependency of the relation

  19. Identification and characterization of a tandem repeat in exon III of the dopamine receptor D4 (DRD4) gene in cetaceans

    DEFF Research Database (Denmark)

    Mogensen, Line; Kinze, Carl Christian; Werge, Thomas

    2006-01-01

    A large number of mammalian species harbor a tandem repeat in exon III of the gene encoding dopamine receptor D4 (DRD4), a receptor associated with cognitive functions. In this study, a DRD4 gene exon III tandem repeat from the order Cetacea was identified and characterized. Included in our study...

  20. The BPS spectrum of the 4d {N}=2 SCFT's H 1, H 2, D 4, E 6, E 7, E 8

    Science.gov (United States)

    Cecotti, Sergio; Del Zotto, Michele

    2013-06-01

    Extending results of 1112.3984, we show that all rank 1 {N}=2 SCFT's in the sequence H 1, H 2, D 4 E 6, E 7, E 8 have canonical finite BPS chambers containing precisely 2 h(F) = 12(∆ - 1) hypermultiplets. The BPS spectrum of the canonical BPS chambers saturates the conformal central charge c, and satisfies some intriguing numerology.

  1. Genomic characterization and linkage mapping of the apple allergen genes Mal d 2 (thaumatin-like protein) and Mal d 4 (profilin)

    NARCIS (Netherlands)

    Gao, Z.S.; Weg, van de W.E.; Schaart, J.G.; Arkel, van G.; Breiteneder, H.; Hoffmann-Sommergruber, K.; Gilissen, L.J.W.J.

    2005-01-01

    Four classes of apple allergens (Mal d 1, ¿2, ¿3 and ¿4) have been reported. By using PCR cloning and sequencing approaches, we obtained genomic sequences of Mal d 2 (thaumatin-like protein) and Mal d 4 (profilin) from the cvs Prima and Fiesta, the two parents of a European reference mapping

  2. Regulator of G protein signaling 2 (RGS2 and RGS4 form distinct G protein-dependent complexes with protease activated-receptor 1 (PAR1 in live cells.

    Directory of Open Access Journals (Sweden)

    Sungho Ghil

    Full Text Available Protease-activated receptor 1 (PAR1 is a G-protein coupled receptor (GPCR that is activated by natural proteases to regulate many physiological actions. We previously reported that PAR1 couples to Gi, Gq and G12 to activate linked signaling pathways. Regulators of G protein signaling (RGS proteins serve as GTPase activating proteins to inhibit GPCR/G protein signaling. Some RGS proteins interact directly with certain GPCRs to modulate their signals, though cellular mechanisms dictating selective RGS/GPCR coupling are poorly understood. Here, using bioluminescence resonance energy transfer (BRET, we tested whether RGS2 and RGS4 bind to PAR1 in live COS-7 cells to regulate PAR1/Gα-mediated signaling. We report that PAR1 selectively interacts with either RGS2 or RGS4 in a G protein-dependent manner. Very little BRET activity is observed between PAR1-Venus (PAR1-Ven and either RGS2-Luciferase (RGS2-Luc or RGS4-Luc in the absence of Gα. However, in the presence of specific Gα subunits, BRET activity was markedly enhanced between PAR1-RGS2 by Gαq/11, and PAR1-RGS4 by Gαo, but not by other Gα subunits. Gαq/11-YFP/RGS2-Luc BRET activity is promoted by PAR1 and is markedly enhanced by agonist (TFLLR stimulation. However, PAR1-Ven/RGS-Luc BRET activity was blocked by a PAR1 mutant (R205A that eliminates PAR1-Gq/11 coupling. The purified intracellular third loop of PAR1 binds directly to purified His-RGS2 or His-RGS4. In cells, RGS2 and RGS4 inhibited PAR1/Gα-mediated calcium and MAPK/ERK signaling, respectively, but not RhoA signaling. Our findings indicate that RGS2 and RGS4 interact directly with PAR1 in Gα-dependent manner to modulate PAR1/Gα-mediated signaling, and highlight a cellular mechanism for selective GPCR/G protein/RGS coupling.

  3. Synthesis of n.c.a. 18F-fluorinated NMDA- and D4-receptor ligands via [18F]fluorobenzenes

    International Nuclear Information System (INIS)

    Ludwig, T.

    2005-11-01

    In this thesis new strategies were developed and evaluated for the no-carrier-added (n.c.a.) 18 F-labelling of receptor ligands as radiodiagnostics for characterization of brain receptors using positron-emission-tomography (PET). Special emphasis was placed on the synthesis of n.c.a. (±)-3-(4-hydroxy-4-(4-[ 18 F]fluorophenyl)-piperidin-l-yl)chroman-4,7-diol, a ligand with high affinity for the NR2B subtype of NMDA receptors and n.c.a. (3-(4-[ 18 F]fluorphenoxy)propyl)-(2-(4-tolylphenoxy)ethyl)amine ([ 18 F]FPTEA) a dopamine D 4 receptor ligand. In order to synthesize n.c.a. (±)-3-(4-hydroxy-4-(4-[ 18 F]fluorophenyl)-piperidin-l-yl)chroman-4,7-diol the 18 F-fluoroarylation method via metallorganic intermediates was modified and improved. The suitability of the organometallic 18 F-fluoroarylation agents was proven with several model compounds. High radiochemical yields of 20-30% were obtained also with piperidinone-derivatives. The preparation of a suitable precursor for the synthesis of the NMDA receptor ligand, however, could not be achieved by synthesis of appropriate 1,3-dioxolane protected piperidinone derivatives. Further, the synthesis of n.c.a. ([ 18 F]fluoroaryloxy)alkylamines via n.c.a. 4-[ 18 F]fluorophenol was developed and evaluated. The synthesis of n.c.a. [ 18 F]fluoroarylethers with corresponding model compounds was optimized and led to a radiochemical yield of 25-60%, depending on the alkylhalide used. The preparation of n.c.a. 1-(3-bromopropoxy)-4-[ 18 F]fluorobenzene proved advantageous in comparison to direct use of 4-[ 18 ]fluorophenol for coupling with a corresponding N-protected precursor for the synthesis of n.c.a. [ 18 F]FPTEA. With regard to the radiochemical yields and the loss of activity during the synthesis and isolation of n.c.a. 4-[ 18 F]fluorophenol and n.c.a. 1-(3-bromopropoxy)-4-[ 18 F]fluorobenzene, [ 18 F]FPTEA was obtained by reaction with 2-(4-tolyloxy)ethylamine in radiochemical yields of about 25-30% in ethanol or 2-butanone

  4. Interleukin-22 (IL-22) activates the JAK/STAT, ERK, JNK, and p38 MAP kinase pathways in a rat hepatoma cell line - Pathways that are shared with and distinct from IL-10

    NARCIS (Netherlands)

    Lejeune, D; Dumoutier, L; Constantinescu, S; Kruijer, W; Schuringa, JJ; Renauld, JC

    2002-01-01

    IL (interleukin)-22 is an IL-10-related cytokine; its main biological activity known thus far is the induction of acute phase reactants in liver and pancreas. IL-22 signals through a receptor that is composed of two chains from the class II cytokine receptor family: IL-22R (also called

  5. Leptin Reduces the Expression and Increases the Phosphorylation of the Negative Regulators of GLUT4 Traffic TBC1D1 and TBC1D4 in Muscle of ob/ob Mice

    Science.gov (United States)

    Sáinz, Neira; Rodríguez, Amaia; Catalán, Victoria; Becerril, Sara; Ramírez, Beatriz; Lancha, Andoni; Burgos-Ramos, Emma; Gómez-Ambrosi, Javier; Frühbeck, Gema

    2012-01-01

    Leptin improves insulin sensitivity in skeletal muscle. Our goal was to determine whether proteins controlling GLUT4 traffic are altered by leptin deficiency and in vivo leptin administration in skeletal muscle of wild type and ob/ob mice. Leptin-deficient ob/ob mice were divided in three groups: control, leptin-treated (1 mg/kg/d) and leptin pair-fed ob/ob mice. Microarray analysis revealed that 1,546 and 1,127 genes were regulated by leptin deficiency and leptin treatment, respectively. Among these, we identified 24 genes involved in intracellular vesicle-mediated transport in ob/ob mice. TBC1 domain family, member 1 (Tbc1d1), a negative regulator of GLUT4 translocation, was up-regulated (P = 0.001) in ob/ob mice as compared to wild types. Importantly, leptin treatment reduced the transcript levels of Tbc1d1 (P<0.001) and Tbc1d4 (P = 0.004) in the leptin-treated ob/ob as compared to pair-fed ob/ob animals. In addition, phosphorylation levels of TBC1D1 and TBC1D4 were enhanced in leptin-treated ob/ob as compared to control ob/ob (P = 0.015 and P = 0.023, respectively) and pair-fed ob/ob (P = 0.036 and P = 0.034, respectively) mice. Despite similar GLUT4 protein expression in wild type and ob/ob groups a different immunolocalization of this protein was evidenced in muscle sections. Leptin treatment increased GLUT4 immunoreactivity in gastrocnemius and extensor digitorum longus sections of leptin-treated ob/ob mice. Moreover, GLUT4 protein detected in immunoprecipitates from TBC1D4 was reduced by leptin replacement compared to control ob/ob (P = 0.013) and pair-fed ob/ob (P = 0.037) mice. Our findings suggest that leptin enhances the intracellular GLUT4 transport in skeletal muscle of ob/ob animals by reducing the expression and activity of the negative regulators of GLUT4 traffic TBC1D1 and TBC1D4. PMID:22253718

  6. Radiochemical synthesis of 3-(4-[18F] Fluorophenyl)-8-hydroxy-1, 2, 3, 4-tetrahydrochromeno [3, 4-c] pyridin-5-one: A putative dopamine D$4 receptor PET imaging agent

    International Nuclear Information System (INIS)

    Li, G.C.; Yin, D.Z.; Wang, M.W.; Cheng, D.F.; Wang, Y.X.

    2005-01-01

    Introduction: The dopamine D 4 receptor has lately received increasing interest since it has been hypothesized to be involved in the pathology and pharmacotherapy of schizophrenia. While this receptor is expressed in lower density in various extrastriatal brain regions and its distribution is still unclear due to the lack of suitable imaging agent and its level change in schizophrenia is controversial. Herein, based on the structure-activity analysis of chromeno[3, 4-c]pyridine- 5-ones as potential dopamine D 4 receptor ligands, a putative D 4 subtype positron emission tomography (PET) radioligand, 3-(4-[ 18 F]fluorophenyl)-8-hydroxy-1, 2, 3, 4-tetrahydrochromeno [3, 4-c]pyridin-5-one ([ 18 F]FHTP), was designed and synthesized. Methods: The radiochemical synthesis route was shown in Figure 1. [ 18 F]Fluoride was produced with a Cyclone-30 (IBA, Belgium) by 18 O(p, n) 18 F reaction using enriched 18 O-H 2 O and eluted from a Dowex 1-X8 anion-exchange column with aqueous potassium carbonate (20 mg/mL). 4-[ 18 F]Fluorobenzaldehyde was prepared according to the method reported by Alan A. Wilson and et al.. Then, 8-hydroxy-1, 2, 3, 4-tetrahydrochromeno [3, 4-c]pyridin-5-one, sodium cyanoborohydride, methanol and acetic acid were added to the dry residue, The mixture was then sealed and heated at 120 degree C for 12 min. At the end of the reaction, the mixture was cooled, diluted with ethyl acetate and washed with water. The extracted organic layer was passed through a small anhydrous magnesium sulfate column. After removal of the solvents in the mixture at 50 degree C under a stream of nitrogen, the obtained residue was redissolved in methanol and purified with a semi-preparative HPLC system, then the desired product was collected. Results: The radiochemical synthesis of [ 18 F]FHTP took around 110 min at EOS with an overall radiochemical yield 19% (decay-corrected) and its radiochemical purity was higher than 95%. Conclusion: A presumed dopamine D 4 receptor PET

  7. Social conformity despite individual preferences for distinctiveness.

    Science.gov (United States)

    Smaldino, Paul E; Epstein, Joshua M

    2015-03-01

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

  8. Regulation of T cell activation by HIV-1 accessory proteins: Vpr acts via distinct mechanisms to cooperate with Nef in NFAT-directed gene expression and to promote transactivation by CREB

    International Nuclear Information System (INIS)

    Lahti, Anna L.; Manninen, Aki; Saksela, Kalle

    2003-01-01

    Nef and Vpr are lentiviral accessory proteins that have been implicated in regulation of cellular gene expression. We noticed that Vpr can potentiate Nef-induced activation of nuclear factor of activated T cells (NFAT)-dependent transcription. Unlike Nef, which stimulated calcium signaling to activate NFAT, Vpr functioned farther downstream. Similar to the positive effects of Vpr on most of the transcriptional test systems that we used, potentiation of NFAT-directed gene expression was relatively modest in magnitude (two- to threefold) and depended on the cell cycle-arresting capacity of Vpr. By contrast, we found that Vpr could cause more than fivefold upregulation of cyclic AMP response element (CRE)-directed transcription via a mechanism that did not require Vpr-induced G2/M arrest. This effect, however, was only evident under suboptimal conditions known to lead to serine phosphorylation of the CRE binding factor (CREB) but not to CREB-dependent gene expression. This suggested that Vpr may act by stabilizing interactions with CREB and its transcriptional cofactor CREB binding protein (CBP). Indeed, this effect could be blocked by cotransfection of the adenoviral CBP inhibitor E1A. These results provide additional evidence for cell cycle-independent regulation of gene expression by Vpr and implicate CREB as a potentially important target for Vpr action in HIV-infected host cells

  9. Theoretical insight into the distinct photocatalytic activity between NiO{sub x} and CoO{sub x} loaded Ta{sub 3}N{sub 5} photocatalyst

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Kenan; Li, Yuanyuan; Zhang, Qing [Institute of Environmental and Analytical Sciences, College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan, 475004 (China); Wang, Li, E-mail: chemwangl@henu.edu.cn [Institute of Environmental and Analytical Sciences, College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan, 475004 (China); Zhang, Jinglai, E-mail: zhangjinglai@henu.edu.cn [Institute of Environmental and Analytical Sciences, College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan, 475004 (China); Zhou, Xin, E-mail: zhouxin@dlu.edu.cn [College of Environment and Chemical Engineering, Dalian University, Dalian, 116622 (China)

    2017-05-31

    Highlights: • Highly active photocatalytic Ta{sub 3}N{sub 5} loaded with CoO{sub x} and NiO{sub x}. • Exploring the stable structure and the electronic properties by DFT calculations. • Investigating the behavior of water adsorption on the surface of photocatalytic. - Abstract: Experiments found that cocatalysts play an important role in influencing the efficiency of photocatalysis and photoelectrochemical water splitting. However, how to choose proper cocatalysts in certain photocatalytic system is still a challenging question. In this work, the first-principles density functional theory is employed to explore two photocatalysts with different photocatalytic activity, CoO{sub x} and NiO{sub x} loaded Ta{sub 3}N{sub 5}, including finding the stable structure of metal oxide adsorbed surface, analyzing the electronic properties, and investigating the behavior of water adsorption. Our results indicate that the structural match between cluster and surface and less distortion of interfacial structure are benefit to the stability of the whole system. Water dissociation tends to occur at the interface between metal oxide cluster and Ta{sub 3}N{sub 5} surface. Combining observations in experiments with our calculated results, we propose that the obvious difference of photocatalytic activities in CoO{sub x}/Ta{sub 3}N{sub 5} and NiO{sub x}/Ta{sub 3}N{sub 5} is possibly related to whether there are impurity states located in the middle of band gap, which has adverse effect on the separation of photo-generated electrons and holes.

  10. Early-to-mid gestation fetal testosterone increases right hand 2D:4D finger length ratio in polycystic ovary syndrome-like monkeys.

    Directory of Open Access Journals (Sweden)

    Andrew D Abbott

    Full Text Available A smaller length ratio for the second relative to the fourth finger (2D:4D is repeatedly associated with fetal male-typical testosterone (T and is implicated as a biomarker for a variety of traits and susceptibility to a number of diseases, but no experimental human studies have been performed. The present study utilizes the rhesus monkey, a close relative of humans, and employs discrete gestational exposure of female monkeys to fetal male-typical T levels for 15-35 days during early-to-mid (40-76 days; n = 7 or late (94-139 days; n = 7 gestation (term: 165 days by daily subcutaneous injection of their dams with 10 mg T propionate. Such gestational exposures are known to enhance male-typical behavior. In this study, compared to control females (n = 19, only early-to-mid gestation T exposure virilizes female external genitalia while increasing 2D:4D ratio in the right hand (RH by male-like elongation of RH2D. RH2D length and 2D:4D positively correlate with androgen-dependent anogenital distance (AG, and RH2D and AG positively correlate with duration of early-to-mid gestation T exposure. Male monkeys (n = 9 exhibit a sexually dimorphic 2D:4D in the right foot, but this trait is not emulated by early-to-mid or late gestation T exposed females. X-ray determined phalanx measurements indicate elongated finger and toe phalanx length in males, but no other phalanx-related differences. Discrete T exposure during early-to-mid gestation in female rhesus monkeys thus appears to increase RH2D:4D through right-side biased, non-skeletal tissue growth. As variation in timing and duration of gestational T exposure alter male-like dimensions of RH2D independently of RH4D, postnatal RH2D:4D provides a complex biomarker for fetal T exposure.

  11. Identity-specific motivation: How distinct identities direct self-regulation across distinct situations.

    Science.gov (United States)

    Browman, Alexander S; Destin, Mesmin; Molden, Daniel C

    2017-12-01

    Research on self-regulation has traditionally emphasized that people's thoughts and actions are guided by either (a) domain-general motivations that emerge from a cumulative history of life experiences, or (b) situation-specific motivations that emerge in immediate response to the incentives present in a particular context. However, more recent studies have illustrated the importance of understanding the interplay between such domain-general and situation-specific motivations across the types of contexts people regularly encounter. The present research, therefore, expands existing perspectives on self-regulation by investigating how people's identities -the internalized roles, relationships, and social group memberships that define who they are-systemically guide when and how different domain-general motivations are activated within specific types of situations. Using the motivational framework described by regulatory focus theory (Higgins, 1997), Studies 1 and 2 demonstrate that people indeed have distinct, identity-specific motivations that uniquely influence their current self-regulation when such identities are active. Studies 3-5 then begin to explore how identity-specific motivations are situated within people's larger self-concept. Studies 3a and 3b demonstrate that the less compatible people's specific identities, the more distinct are the motivations connected to those identities. Studies 4-5 then provide some initial, suggestive evidence that identity-specific motivations are not a separate, superordinate feature of people's identities that then alter how they pursue any subordinate, identity-relevant traits, but instead that such motivations emerge from the cumulative motivational significance of the subordinate traits to which the identities themselves become attached. Implications for understanding the role of the self-concept in self-regulation are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  12. Validity of Sensory Systems as Distinct Constructs

    OpenAIRE

    Su, Chia-Ting; Parham, L. Diane

    2014-01-01

    Confirmatory factor analysis testing whether sensory questionnaire items represented distinct sensory system constructs found, using data from two age groups, that such constructs can be measured validly using questionnaire data.

  13. Visual distinctiveness can enhance recency effects.

    Science.gov (United States)

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

    1995-05-01

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

  14. Chemical effects of 13N produced by recoil protons and deuterons in pile-irradiated methanol and methanol-d4

    International Nuclear Information System (INIS)

    Sensui, Y.; Tomura, K.; Matsuura, T.

    1982-01-01

    The stabilized chemical forms of 13 N resulting from the reactions 13 C(p,n) 13 N by a recoil proton and 12 C(d,n) 13 N by a recoil deuteron, were studied in pile-irradiated methanol and methanol-d 4 in the temperature range from 77 to 295 K. Contrary to the target of benzene, cyclohexane, acetone and diethyl ether previously studied, the relative yield of 13 N-compounds did not depend on the irradiation temperature in the present media. In the yield of 13 N-compounds no marked change was observed between methanol and methanol-d 4 , differing from the results between benzene and benzene-d 6 . A mechanism is proposed to explain the results. (author)

  15. Is the ground state of 5d4 double-perovskite Iridate Ba2YIrO6 magnetic or nonmagnetic?

    Science.gov (United States)

    Gong, Hoshin; Kim, Kyoo; Kim, Beom Hyun; Kim, Bongjae; Kim, Junwon; Min, B. I.

    2018-05-01

    We have investigated electronic structures and magnetic properties of double perovskite Iridate Ba2YIrO6 with 5d4 configuration, employing the exact diagonalization method for multi-site clusters. We have considered a many-body Hamiltonian for all d states (eg and t2g) including all relevant physical parameters such as the Coulomb correlation, spin-orbit coupling, crystal-field effect, and Hund coupling. We have found that the ground state of Ba2YIrO6 is nonmagnetic and that the Hund coupling plays an important role in the magnetic properties of the 5d4 systems, unlike the well-studied 5d5 systems.

  16. The R-matrix of the Uq(d4(3)) algebra and g2(1) affine Toda field theory

    International Nuclear Information System (INIS)

    Takacs, G.

    1997-01-01

    The R-matrix of the U q (d 4 (3) ) algebra is constructed in the 8-dimensional fundamental representation. Using this result, an exact S-matrix is conjectured for the imaginary coupled g 2 (1) affine Toda field theory, the structure of which is found to be very similar to the previously investigated S-matrix of d 4 (3) Toda theory. It is shown that this S-matrix is consistent with the results for the case of real coupling using the breather-particle correspondence. For q a root of unity it is argued that the theory can be restricted to yield Φ(11 vertical stroke 12) perturbations of WA 2 minimal models. (orig.)

  17. Evolutionary Dynamics of Pathoadaptation Revealed by Three Independent Acquisitions of the VirB/D4 Type IV Secretion System in Bartonella.

    Science.gov (United States)

    Harms, Alexander; Segers, Francisca H I D; Quebatte, Maxime; Mistl, Claudia; Manfredi, Pablo; Körner, Jonas; Chomel, Bruno B; Kosoy, Michael; Maruyama, Soichi; Engel, Philipp; Dehio, Christoph

    2017-03-01

    The α-proteobacterial genus Bartonella comprises a group of ubiquitous mammalian pathogens that are studied as a model for the evolution of bacterial pathogenesis. Vast abundance of two particular phylogenetic lineages of Bartonella had been linked to enhanced host adaptability enabled by lineage-specific acquisition of a VirB/D4 type IV secretion system (T4SS) and parallel evolution of complex effector repertoires. However, the limited availability of genome sequences from one of those lineages as well as other, remote branches of Bartonella has so far hampered comprehensive understanding of how the VirB/D4 T4SS and its effectors called Beps have shaped Bartonella evolution. Here, we report the discovery of a third repertoire of Beps associated with the VirB/D4 T4SS of B. ancashensis, a novel human pathogen that lacks any signs of host adaptability and is only distantly related to the two species-rich lineages encoding a VirB/D4 T4SS. Furthermore, sequencing of ten new Bartonella isolates from under-sampled lineages enabled combined in silico analyses and wet lab experiments that suggest several parallel layers of functional diversification during evolution of the three Bep repertoires from a single ancestral effector. Our analyses show that the Beps of B. ancashensis share many features with the two other repertoires, but may represent a more ancestral state that has not yet unleashed the adaptive potential of such an effector set. We anticipate that the effectors of B. ancashensis will enable future studies to dissect the evolutionary history of Bartonella effectors and help unraveling the evolutionary forces underlying bacterial host adaptation. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  18. Age at menarche and digit ratio (2D:4D): relationships with body dissatisfaction, drive for thinness, and bulimia symptoms in women.

    Science.gov (United States)

    Oinonen, Kirsten A; Bird, Jessica L

    2012-03-01

    This study examined the hypothesis that lower prenatal androgen exposure and earlier puberty are associated with more dysfunctional eating attitudes and behaviors. Relationships between both age at menarche (AAM) and 2D:4D (a marker of prenatal androgen exposure), and EDI-2-Body Dissatisfaction, EDI-2-Drive for Thinness, and EDI-2-Bulimia scores, were examined in women using correlations and regressions. Earlier menarche was associated with higher drive for thinness after controlling for BMI and negative affect, but only in women who were not exclusively heterosexual. Higher 2D:4D was associated with higher Bulimia and Body Dissatisfaction scores, but only in exclusively heterosexual women, and relationships disappeared when covariates were controlled. Later AAM and higher 2D:4D were unique predictors of higher Bulimia scores for exclusive heterosexuals when BMI was controlled. These findings suggest future research should examine sexual orientation as a mediator or moderator of prenatal and postnatal organizational hormonal effects on women's disordered eating attitudes and behaviors. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Emergence and fate of cyclic volatile polydimethylsiloxanes (D4, D5) in municipal waste streams: release mechanisms, partitioning and persistence in air, water, soil and sediments.

    Science.gov (United States)

    Surita, Sharon C; Tansel, Berrin

    2014-01-15

    Siloxane use in consumer products (i.e., fabrics, paper, concrete, wood, adhesive surfaces) has significantly increased in recent years due to their excellent water repelling and antimicrobial characteristics. The objectives of this study were to evaluate the release mechanisms of two siloxane compounds, octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5), which have been detected both at landfills and wastewater treatment plants, estimate persistence times in different media, and project release quantities over time in relation to their increasing use. Analyses were conducted based on fate and transport mechanisms after siloxanes enter waste streams. Due to their high volatility, the majority of D4 and D5 end up in the biogas during decomposition. D5 is about ten times more likely to partition into the solid phase (i.e., soil, biosolids). D5 concentrations in the wastewater influent and biogas are about 16 times and 18 times higher respectively, in comparison to the detected levels of D4. © 2013 Elsevier B.V. All rights reserved.

  20. Generation, Testing, and Validation of a WIMS-D/4 Multigroup Cross-Section Library Based on the JENDL-3.2 Nuclear Data

    International Nuclear Information System (INIS)

    Rahman, Mafizur; Takano, Hideki

    2001-01-01

    A new 69-group library of multigroup constants for the lattice code WIMS-D/4 has been generated with an improved resonance treatment, processing nuclear data from JENDL-3.2 by NJOY91.108. A parallel ENDF/B-VI based library has also been constructed for intercomparison of results. Benchmark calculations for a number of thermal reactor critical assemblies of both uranium and plutonium fuels have been performed with the code WIMS-D/4.1 with its three different libraries: the original WIMS library (NEA-0329/10) and the new ENDF/B-VI and JENDL-3.2 based libraries. The results calculated with both ENDF and JENDL based libraries show a similar tendency and are found in better agreement with the experimental values. Benchmark parameters are further calculated with the comprehensive lattice code SRAC95. The results from SRAC95 and WIMS-D/4.1 (both using JENDL-3.2 based libraries) agree well with each other. The new library is also verified for its applicability to mixed-oxide cores of varying plutonium contents

  1. DNA replication timing is maintained genome-wide in primary human myoblasts independent of D4Z4 contraction in FSH muscular dystrophy.

    Directory of Open Access Journals (Sweden)

    Benjamin D Pope

    Full Text Available Facioscapulohumeral muscular dystrophy (FSHD is linked to contraction of an array of tandem 3.3-kb repeats (D4Z4 at 4q35.2 from 11-100 copies to 1-10 copies. The extent to which D4Z4 contraction at 4q35.2 affects overall 4q35.2 chromatin organization remains unclear. Because DNA replication timing is highly predictive of long-range chromatin interactions, we generated genome-wide replication-timing profiles for FSHD and control myogenic precursor cells. We compared non-immortalized myoblasts from four FSHD patients and three control individuals to each other and to a variety of other human cell types. This study also represents the first genome-wide comparison of replication timing profiles in non-immortalized human cell cultures. Myoblasts from both control and FSHD individuals all shared a myoblast-specific replication profile. In contrast, male and female individuals were readily distinguished by monoallelic differences in replication timing at DXZ4 and other regions across the X chromosome affected by X inactivation. We conclude that replication timing is a robust cell-type specific feature that is unaffected by FSHD-related D4Z4 contraction.

  2. Data Assimilation of Lightning using 1D+3D/4D WRF Var Assimilation Schemes with Non-Linear Observation Operators

    Science.gov (United States)

    Navon, M. I.; Stefanescu, R.; Fuelberg, H. E.; Marchand, M.

    2012-12-01

    NASA's launch of the GOES-R Lightning Mapper (GLM) in 2015 will provide continuous, full disc, high resolution total lightning (IC + CG) data. The data will be available at a horizontal resolution of approximately 9 km. Compared to other types of data, the assimilation of lightning data into operational numerical models has received relatively little attention. Previous efforts of lightning assimilation mostly have employed nudging. This paper will describe the implementation of 1D+3D/4D Var assimilation schemes of existing ground-based WTLN (Worldwide Total Lightning Network) lightning observations using non-linear observation operators in the incremental WRFDA system. To mimic the expected output of GLM, the WTLN data were used to generate lightning super-observations characterized by flash rates/81 km2/20 min. A major difficulty associated with variational approaches is the complexity of the observation operator that defines the model equivalent of lightning. We use Convective Available Potential Energy (CAPE) as a proxy between lightning data and model variables. This operator is highly nonlinear. Marecal and Mahfouf (2003) have shown that nonlinearities can prevent direct assimilation of rainfall rates in the ECMWF 4D-VAR (using the incremental formulation proposed by Courtier et al. (1994)) from being successful. Using data from the 2011 Tuscaloosa, AL tornado outbreak, we have proved that the direct assimilation of lightning data into the WRF 3D/4D - Var systems is limited due to this incremental approach. Severe threshold limits must be imposed on the innovation vectors to obtain an improved analysis. We have implemented 1D+3D/4D Var schemes to assimilate lightning observations into the WRF model. Their use avoids innovation vector constrains from preventing the inclusion of a greater number of lightning observations Their use also minimizes the problem that nonlinearities in the moist convective scheme can introduce discontinuities in the cost function

  3. A new practical method for the preparation of [3H6]-leukotrienes C4 and D4

    International Nuclear Information System (INIS)

    Belley, M.L.; Gareau, Y.; Zamboni, R.J.; Ahern, D.G.; Yang Hong

    1995-01-01

    A new method for the synthesis of highly deuterated or tritiated leukotrienes was developed. The higher reactivity of a terminal alkene compared to a 1,2-disubstituted one permitted the selective deuteration or tritiation of the diyne 14,15,19,19,20,20-hexadehydro LTC 4 troester 1. After hydrolysis, LTC 4 was obtained in 36% overall yield. An average of seven deuterium or tritium atoms was incorporated and the specific activity of the tritiated LTC 4 was greater than 180Ci/mmol. 1 was obtained from the addition of glutathione to 14,15,19,19,20,20-hexadehydro LTA 4 ethyl ester which was the product of a Wittig reaction between (3,8-nonanediyn-1-yl) triphenylphosphonium iodide and 5(S), 6(S), 7(E), 9(E) ethyl 5,6-epoxy-11-oxo-7,9-undecadienoate. (Author)

  4. Neural correlates of the food/non-food visual distinction.

    Science.gov (United States)

    Tsourides, Kleovoulos; Shariat, Shahriar; Nejati, Hossein; Gandhi, Tapan K; Cardinaux, Annie; Simons, Christopher T; Cheung, Ngai-Man; Pavlovic, Vladimir; Sinha, Pawan

    2016-03-01

    An evolutionarily ancient skill we possess is the ability to distinguish between food and non-food. Our goal here is to identify the neural correlates of visually driven 'edible-inedible' perceptual distinction. We also investigate correlates of the finer-grained likability assessment. Our stimuli depicted food or non-food items with sub-classes of appealing or unappealing exemplars. Using data-classification techniques drawn from machine-learning, as well as evoked-response analyses, we sought to determine whether these four classes of stimuli could be distinguished based on the patterns of brain activity they elicited. Subjects viewed 200 images while in a MEG scanner. Our analyses yielded two successes and a surprising failure. The food/non-food distinction had a robust neural counterpart and emerged as early as 85 ms post-stimulus onset. The likable/non-likable distinction too was evident in the neural signals when food and non-food stimuli were grouped together, or when only the non-food stimuli were included in the analyses. However, we were unable to identify any neural correlates of this distinction when limiting the analyses only to food stimuli. Taken together, these positive and negative results further our understanding of the substrates of a set of ecologically important judgments and have clinical implications for conditions like eating-disorders and anhedonia. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Distinctiveness of Initial Preform Properties in Renovation

    Directory of Open Access Journals (Sweden)

    V. M. Yaroslavtsev

    2015-01-01

    Full Text Available Technologies of renovation form a special group of resource-and energy saving technological processes as they are, by definition, already aimed either at increasing resource of the objects satisfying needs of the society life support and practical activities in different spheres, or at extension of their life cycle including a reuse of material from which they are made. Renovation is used where there is a material object, which does not meet requirements of standard or technical documentation.A characteristic feature of the renovation technologies is lack of procedure for a choice of the preform as in all cases an initial preform is the renovation object itself. Thus each object, acting as an initial preform, has the exclusively individual properties, including technological ones.Distinctiveness of renovation object properties is correlated, first of all, with the personified conditions of formation and (or change of condition of their properties in time at all stages of life cycle (production – transportation – warehousing – operation starting with a preform material when manufacturing under all types of loadings (technological and operational. As a result each object forms its "history" of loading and damages and, therefore, its information base which has to consider the phenomenon of “heredity of life cycle”. The term "heredity of life cycle" characterizes information support of object at any moment under review, including both information of technological inheritance, and data of operational heredity.As a result at every moment of time we have a product with a set of new, uncertain properties caused by the phenomena of heredity of life cycle. These properties are individual for each object to be renovated, which changed its status for the status of initial preform for different types of renovation technologies. This is one of the most important distinctions of renovation technology from the technology used to manufacture a new

  6. Distinctiveness of Saudi Arabian EFL Learners

    Directory of Open Access Journals (Sweden)

    Manssour Habbash

    2016-04-01

    Full Text Available In view of the increasing concern among English language teachers dealing with students from Saudi Arabia, as it manifests in TESOL community discussions, about the uniqueness of Saudi Arabian EFL learners, this paper attempts to document the outcome of a study of their distinctiveness from the perspective of expatriate teachers working for PYPs (Preparatory Year Programs in Saudi Arabia. This study examines the distinctiveness with regard to the learning attitudes of Saudi students that are often cultivated by the culture and academic environment in their homeland. Employing an emic approach for collecting the required data an analysis was carried out in light of the other studies on ‘education’ in Saudi Arabia that have particular reference to the factors that can positively influence student motivation, student success and the academic environment. The findings were used in constructing the rationale behind such distinctiveness. Assuming that the outcome of the discussion on the findings of this exploration can be helpful for teachers in adapting their teaching methodology and improving their teacher efficacy in dealing with students both from the kingdom and in the kingdom, some recommendations are made. Keywords: China Distinctiveness, Saudi Arabian University context, Expatriate teachers’ perspective, Distinctiveness Theory

  7. Cysteinyl leukotrienes C4 and D4 downregulate human mast cell expression of toll-like receptors 1 through 7.

    Science.gov (United States)

    Karpov, V; Ilarraza, R; Catalli, A; Kulka, M

    2018-01-01

    Cysteinyl leukotrienes (CysLT) are potent inflammatory lipid molecules that mediate some of the pathophysiological responses associated with asthma such as bronchoconstriction, vasodilation and increased microvascular permeability. As a result, CysLT receptor antagonists (LRA), such as montelukast, have been used to effectively treat patients with asthma. We have recently shown that mast cells are necessary modulators of innate immune responses to bacterial infection and an important component of this innate immune response may involve the production of CysLT. However, the effect of LRA on innate immune receptors, particularly on allergic effector cells, is unknown. This study determined the effect of CysLT on toll-like receptor (TLR) expression by the human mast cell line LAD2. Real-time PCR analysis determined that LTC4, LTD4 and LTE4 downregulated mRNA expression of several TLR. Specifically in human CD34+-derived human mast cells (HuMC), LTC4 inhibited expression of TLR1, 2, 4, 5, 6 and 7 while LTD4 inhibited expression of TLR1-7. Montelukast blocked LTC4-mediated downregulation of all TLR, suggesting that these effects were mediated by activation of the CysLT1 receptor (CysLT1R). Flow cytometry analysis confirmed that LTC4 downregulated surface expression of TLR2 which was blocked by montelukast. These data show that CysLT can modulate human mast cell expression of TLR and that montelukast may be beneficial for innate immune responses mediated by mast cells.

  8. On Hobbes’s distinction of accidents

    Directory of Open Access Journals (Sweden)

    Lupoli Agostino

    2012-06-01

    Full Text Available An interpolation introduced by K. Schuhmann in his critical edition of "De corpore" (chap. VI, § 13 diametrically overturns the meaning of Hobbes’s doctrine of distinction of accidents in comparison with all previous editions. The article focuses on the complexity of this crucial juncture in "De corpore" argument on which depends the interpretation of Hobbes’s whole conception of science. It discusses the reasons pro and contra Schuhmann’s interpolation and concludes against it, because it is not compatible with the rationale underlying the complex architecture of "De corpore", which involves a symmetry between the ‘logical’ distinction of accidents and the ‘metaphysical’ distinction of phantasms.

  9. What makes health promotion research distinct?

    Science.gov (United States)

    Woodall, James; Warwick-Booth, Louise; South, Jane; Cross, Ruth

    2018-02-01

    There have been concerns about the decline of health promotion as a practice and discipline and, alongside this, calls for a clearer articulation of health promotion research and what, if anything, makes it distinct. This discussion paper, based on a review of the literature, the authors' own experiences in the field, and a workshop delivered by two of the authors at the 8th Nordic Health Promotion Conference, seeks to state the reasons why health promotion research is distinctive. While by no means exhaustive, the paper suggests four distinctive features. The paper hopes to be a catalyst to enable health promotion researchers to be explicit in their practice and to begin the process of developing an agreed set of research principles.

  10. Intergroup Leadership Across Distinct Subgroups and Identities.

    Science.gov (United States)

    Rast, David E; Hogg, Michael A; van Knippenberg, Daan

    2018-03-01

    Resolving intergroup conflict is a significant and often arduous leadership challenge, yet existing theory and research rarely, if ever, discuss or examine this situation. Leaders confront a significant challenge when they provide leadership across deep divisions between distinct subgroups defined by self-contained identities-The challenge is to avoid provoking subgroup identity distinctiveness threat. Drawing on intergroup leadership theory, three studies were conducted to test the core hypothesis that, where identity threat exists, leaders promoting an intergroup relational identity will be better evaluated and are more effective than leaders promoting a collective identity; in the absence of threat, leaders promoting a collective identity will prevail. Studies 1 and 2 ( N = 170; N = 120) supported this general proposition. Study 3 ( N = 136) extended these findings, showing that leaders promoting an intergroup relational identity, but not a collective identity, improved intergroup attitudes when participants experienced an identity distinctiveness threat.

  11. Distinctive Dynamic Capabilities for New Business Creation

    DEFF Research Database (Denmark)

    Rosenø, Axel; Enkel, Ellen; Mezger, Florian

    2013-01-01

    This study examines the distinctive dynamic capabilities for new business creation in established companies. We argue that these are very different from those for managing incremental innovation within a company's core business. We also propose that such capabilities are needed in both slow...... and fast-paced industries, and that similarities exist across industries. Hence, the study contributes to dynamic capabilities literature by: 1) identifying the distinctive dynamic capabilities for new business creation; 2) shifting focus away from dynamic capabilities in environments characterised by high...... clock-speed and uncertainty towards considering dynamic capabilities for the purpose of developing new businesses, which also implies a high degree of uncertainty. Based on interviews with 33 companies, we identify distinctive dynamic capabilities for new business creation, find that dynamic...

  12. Fermionic bound states in distinct kinklike backgrounds

    Energy Technology Data Exchange (ETDEWEB)

    Bazeia, D. [Universidade Federal da Paraiba, Departamento de Fisica, Joao Pessoa, Paraiba (Brazil); Mohammadi, A. [Universidade Federal de Campina Grande, Departamento de Fisica, Caixa Postal 10071, Campina Grande, Paraiba (Brazil)

    2017-04-15

    This work deals with fermions in the background of distinct localized structures in the two-dimensional spacetime. Although the structures have a similar topological character, which is responsible for the appearance of fractionally charged excitations, we want to investigate how the geometric deformations that appear in the localized structures contribute to the change in the physical properties of the fermionic bound states. We investigate the two-kink and compact kinklike backgrounds, and we consider two distinct boson-fermion interactions, one motivated by supersymmetry and the other described by the standard Yukawa coupling. (orig.)

  13. Two distinct origins for Archean greenstone belts

    Science.gov (United States)

    Smithies, R. Hugh; Ivanic, Tim J.; Lowrey, Jack R.; Morris, Paul A.; Barnes, Stephen J.; Wyche, Stephen; Lu, Yong-Jun

    2018-04-01

    Applying the Th/Yb-Nb/Yb plot of Pearce (2008) to the well-studied Archean greenstone sequences of Western Australia shows that individual volcanic sequences evolved through one of two distinct processes reflecting different modes of crust-mantle interaction. In the Yilgarn Craton, the volcanic stratigraphy of the 2.99-2.71 Ga Youanmi Terrane mainly evolved through processes leading to Th/Yb-Nb/Yb trends with a narrow range of Th/Nb ('constant-Th/Nb' greenstones). In contrast, the 2.71-2.66 Ga volcanic stratigraphy of the Eastern Goldfields Superterrane evolved through processes leading to Th/Yb-Nb/Yb trends showing a continuous range in Th/Nb ('variable-Th/Nb' greenstones). Greenstone sequences of the Pilbara Craton show a similar evolution, with constant-Th/Nb greenstone evolution between 3.13 and 2.95 Ga and variable-Th/Nb greenstone evolution between 3.49 and 3.23 Ga and between 2.77 and 2.68 Ga. The variable-Th/Nb trends dominate greenstone sequences in Australia and worldwide, and are temporally associated with peaks in granite magmatism, which promoted crustal preservation. The increasing Th/Nb in basalts correlates with decreasing εNd, reflecting variable amounts of crustal assimilation during emplacement of mantle-derived magmas. These greenstones are typically accompanied in the early stages by komatiite, and can probably be linked to mantle plume activity. Thus, regions such as the Eastern Goldfields Superterrane simply developed as plume-related rifts over existing granite-greenstone crust - in this case the Youanmi Terrane. Their Th/Nb trends are difficult to reconcile with modern-style subduction processes. The constant-Th/Nb trends may reflect derivation from a mantle source already with a high and constant Th/Nb ratio. This, and a lithological association including boninite-like lavas, basalts, and calc-alkaline andesites, all within a narrow Th/Nb range, resembles compositions typical of modern-style subduction settings. These greenstones are very

  14. The excitation functions of 4s-4p and 3d-4p transitions in Ni atoms sputtered from metallic targets by Ar+ ions

    International Nuclear Information System (INIS)

    Dabrowski, P.; Gabla, L.; Pedrys, R.

    1981-01-01

    The intensities of spectral lines corresponding to 4s-4p and 3d-4p transitions in Ni atoms sputtered from metallic targets by Ar + ions were measured. The energy of primary ions was varied from 4 keV to 10 keV. Both single crystal and polycrystalline targets were used at various temperatures including ferromagnetic and paramagnetic phases. The excitation functions calculated from experimental data can be explained only by the assumption that the promotion of the electrons occurs during energetic binary collisions of atomic particles in the solid. (orig.)

  15. Energy level properties of 4p64d3, 4p64d24f, and 4p54d4 configurations of the W35+ ion

    International Nuclear Information System (INIS)

    Bogdanovich, P.; Kisielius, R.

    2014-01-01

    The ab initio quasirelativistic Hartree–Fock method developed specifically for the calculation of spectroscopic parameters of heavy atoms and highly charged ions was used to derive spectral data for the multicharged tungsten ion W 35+ . The configuration interaction method was applied to include the electron-correlation effects. The relativistic effects were taken into account in the Breit–Pauli approximation for quasirelativistic Hartree–Fock radial orbitals. The energy level spectra, radiative lifetimes τ, and Lande g-factors have been calculated for the 4p 6 4d 3 , 4p 6 4d 2 4f, and 4p 5 4d 4 configurations of the W 35+ ion

  16. High field induced magnetic transitions in the Y0.7E r0.3F e2D4.2 deuteride

    Science.gov (United States)

    Paul-Boncour, V.; Guillot, M.; Isnard, O.; Hoser, A.

    2017-09-01

    The influence of the partial Er for Y substitution on the crystal structure and magnetic properties of YF e2D4.2 has been investigated by high field magnetization and neutron diffraction experiments. Y0.7E r0.3F e2D4.2 compound crystallizes in the same monoclinic structure as YF e2D4.2 described in P c (P1c1) space group with D atoms located in 18 different tetrahedral interstitial sites. A cell volume contraction of 0.6% is observed upon Er substitution, inducing large modification of the magnetic properties. Electronic effect of D insertion as well as lowering of crystal symmetry are important factors determining the magnetic properties of Fe sublattice, which evolves towards more delocalized behavior and modifying the Er-Fe exchange interactions. In the ground state, the Er and Fe moments are arranged ferrimagnetically within the plane perpendicular to the monoclinic b axis and with average moments mEr=6.4 (3 ) μBEr-1 and mFe=2.0 (1 ) μBFe-1 at 10 K. Upon heating, mEr decreases progressively until TEr=55 K . Between 55 K and 75 K, the Fe sublattice undergoes a first-order ferromagnetic-antiferromagnetic (FM-AFM) transition with a cell volume contraction due to the itinerant metamagnetic behavior of one Fe site. In the AFM structure, mFe decreases until the Néel temperature TN=125 K . At high field, two different types of field induced transitions are observed. The Er moments become parallel to the Fe one and saturates to the E r3 + free ion value, leading to an unusual field induced FM arrangement at a transition field BTrans of only 78 kG below 30 K. Then above TM0=66 K , an AFM-FM transition of the Fe sublattice, accompanied by a cell volume increase is observed. BTrans increases linearly versus temperature and with a larger d BTrans/d T slope than for YF e2D4.2 . This has been explained by the additional contribution of Er induced moments above BTrans.

  17. Common and distinct components in data fusion

    DEFF Research Database (Denmark)

    Smilde, Age Klaas; Mage, Ingrid; Næs, Tormod

    2016-01-01

    and understanding their relative merits. This paper provides a unifying framework for this subfield of data fusion by using rigorous arguments from linear algebra. The most frequently used methods for distinguishing common and distinct components are explained in this framework and some practical examples are given...

  18. Knowledge Affords Distinctive Processing in Memory

    Science.gov (United States)

    Hunt, R. Reed; Rawson, Katherine A.

    2011-01-01

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

  19. Distinctiveness of Saudi Arabian EFL Learners

    Science.gov (United States)

    Habbash, Manssour; Idapalapati, Srinivasa Rao

    2016-01-01

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

  20. Cerebral laterality for language is related to adult salivary testosterone levels but not digit ratio (2D:4D) in men: A functional transcranial Doppler ultrasound study.

    Science.gov (United States)

    Papadatou-Pastou, Marietta; Martin, Maryanne

    2017-03-01

    The adequacy of three competing theories of hormonal effects on cerebral laterality are compared using functional transcranial Doppler sonography (fTCD). Thirty-three adult males participated in the study (21 left-handers). Cerebral lateralization was measured by fTCD using an extensively validated word generation task. Adult salivary testosterone (T) and cortisol (C) concentrations were measured by luminescence immunoassay and prenatal T exposure was indirectly estimated by the somatic marker of 2nd to 4th digit length ratio (2D:4D). A significant quadratic relationship between degree of cerebral laterality for language and adult T concentrations was observed, with enhanced T levels for strong left hemisphere dominance and strong right hemisphere dominance. No systematic effects on laterality were found for cortisol or 2D:4D. Findings suggest that higher levels of T are associated with a relatively attenuated degree of interhemispheric sharing of linguistic information, providing support for the callosal and the sexual differentiation hypotheses rather than the Geschwind, Behan and Galaburda (GBG) hypothesis. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Affinity between TBC1D4 (AS160 phosphotyrosine-binding domain and insulin-regulated aminopeptidase cytoplasmic domain measured by isothermal titration calorimetry

    Directory of Open Access Journals (Sweden)

    SangYoun Park*, Keon Young Kim, Sunmin Kim & Young Seok Yu

    2012-06-01

    Full Text Available Uptake of circulating glucose into the cells happens via the insulin-mediated signalling pathway, which translocates the glucosetransporter 4 (GLUT4 vesicles from the intracellular compartmentto the plasma membrane. RabㆍGTPases are involvedin this vesicle trafficking, where RabㆍGTPase-activatingproteins (RabGAP enhance the GTP to GDP hydrolysis.TBC1D4 (AS160 and TBC1D1 are functional RabGAPs in theadipocytes and the skeletonal myocytes, respectively. Theseproteins contain two phosphotyrosine-binding domains (PTBsat the amino-terminus of the catalytic RabGAP domain. Thesecond PTB has been shown to interact with the cytoplasmicregion of the insulin-regulated aminopeptidase (IRAP of theGLUT4 vesicle. In this study, we quantitatively measured the∼μM affinity (KD between TBC1D4 PTB and IRAP using isothermaltitration calorimetry, and further showed that IRAP residues1-49 are the major region mediating this interaction. Wealso demonstrated that the IRAP residues 1-15 are necessarybut not sufficient for the PTB interaction.

  2. D0-D4 brane tachyon condensation to a BPS state and its excitation spectrum in noncommutative super Yang-Mills theory

    International Nuclear Information System (INIS)

    Wimmer, Robert

    2005-01-01

    We investigate the D0-D4-brane system for different B-field backgrounds including the small instanton singularity in noncommutative SYM theory. We discuss the excitation spectrum of the unstable state as well as for the BPS D0-D4 bound state. We compute the tachyon potential which reproduces the complete mass defect. The relevant degrees of freedom are the massless (4,4) strings. Both results are in contrast with existing string field theory calculations. The excitation spectrum of the small instanton is found to be equal to the excitation spectrum of the fluxon solution on R θ 2 x R which we trace back to T-duality. For the effective theory of the (0,0) string excitations we obtain a BFSS matrix model. The number of states in the instanton background changes significantly when the B-field becomes self-dual. This leads us to the proposal of the existence of a phase transition or cross over at self-dual B-field

  3. The Effect of Testosterone Administration and Digit Ratio (2D:4D on Implicit Preference for Status Goods in Healthy Males

    Directory of Open Access Journals (Sweden)

    Yin Wu

    2017-10-01

    Full Text Available Testosterone has been linked to social status seeking in humans. The present study investigated the effects of testosterone administration on implicit and explicit preferences for status goods in healthy male participants (n = 64, using a double-blind, placebo-controlled, between-subjects design. We also investigated the interactive effect between second-to-fourth digit ratio (2D:4D; i.e., a proximal index of prenatal testosterone and testosterone treatment on status preferences. Results showed that testosterone administration has no discernable influence on self-reported willingness-to-pay (i.e., the explicit measure or implicit attitudes towards status goods. Individuals with lower 2D:4D (i.e., more masculine had more positive attitudes for high-status goods on an Implicit Association Task, and this association was abolished with testosterone administration. These data suggest interactive effects of acute testosterone administration and prenatal testosterone exposure on human social status seeking, and highlight the utility of implicit methods for measuring status-related behavior.

  4. Dimorfismo sexual en la proporción entre el segundo y cuarto digito (2D/4D de Gonatodes albogularis (Gekkonidae en Colombia

    Directory of Open Access Journals (Sweden)

    Mauricio Peñuela

    2011-01-01

    Full Text Available La proporción entre el segundo y cuarto dígito (2D/4D ha sido bien estudiada como un dimorfismo sexual que puede resultar de los efectos androgénicos prenatales sobre la expresión de los genes homeobox. Se ha encontrado que este dimorfismo exhibe patrones filogenéticos en el cual las hembras tienen mayor proporción entre dígitos en especies mamíferas y menor proporción entre dígitos en especies de aves y reptiles. Este estudio midió los dígitos segundo y cuarto de todos las extremidades, en 25 especímenes machos y 25 especímenes hembras adultos de Gonatodes albogularis. Se determinó que no existían diferencias significativas entre la proporción (2D/4D en machos y hembras como dimorfismo sexual de la especie. Estos resultados indican que esta especie de lagartija arbórea se desvía de la proporción entre dígitos mostrada por especies diápsida. Posibles factores ambientales asociados son discutidos.

  5. Your fate is in your hands? Handedness, digit ratio (2D:4D), and selection to a national talent development system.

    Science.gov (United States)

    Baker, Joseph; Kungl, Ann-Marie; Pabst, Jan; Strauß, Bernd; Büsch, Dirk; Schorer, Jörg

    2013-01-01

    Over the past decade a small evidence base has highlighted the potential importance of seemingly innocuous variables related to one's hands, such as hand dominance and the relative length of the second and fourth digits (2D:4D ratio), to success in sport. This study compared 2D:4D digit ratio and handedness among handball players selected to advance in a national talent development system with those not selected. Participants included 480 youth handball players (240 females and 240 males) being considered as part of the talent selection programme for the German Youth National team. Hand dominance and digit ratio were compared to age-matched control data using standard t-tests. There was a greater proportion of left-handers compared to the normal population in males but not in females. There was also a lower digit ratio in both females and males. However, there were no differences between those selected for the next stage of talent development and those not selected on either handedness or digit ratio. These results add support for general effects for both digit ratio and handedness in elite handball; however, these factors seem inadequate to explain talent selection decisions at this level.

  6. Self-esteem in remitted patients with mood disorders is not associated with the dopamine receptor D4 and the serotonin transporter genes.

    Science.gov (United States)

    Serretti, A; Macciardi, F; Di Bella, D; Catalano, M; Smeraldi, E

    1998-08-17

    Disturbances of the dopaminergic and serotoninergic neurotransmitter systems have been implicated in the pathogenesis of depressive symptoms. Associations have been reported between markers of the two neurotransmitter systems and the presence of illness or severity of depressive episodes, but no attention has been focused on the periods of remission. The present report focuses on a possible association of self-esteem in remitted mood disorder patients with the functional polymorphism located in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) and the dopamine receptor D4 (DRD4). Inpatients (N=162) affected by bipolar (n=103) and unipolar (n=59) disorder (DSM III-R) were assessed by the Self-Esteem Scale (SES, Rosenberg, 1965) and were typed for DRD4 and 5-HTTLPR (n=58 subjects) variants at the third exon using polymerase chain reaction (PCR) techniques. Neither DRD4 nor 5-HTTLPR variants were associated with SES scores, and consideration of possible stratification effects such as sex and psychiatric diagnosis did not reveal any association either. The serotonin transporter and dopamine receptor D4 genes do not, therefore, influence self-esteem in remitted mood disorder subjects.

  7. Selectivity of recombinant human leukotriene D(4), leukotriene B(4), and lipoxin A(4) receptors with aspirin-triggered 15-epi-LXA(4) and regulation of vascular and inflammatory responses.

    Science.gov (United States)

    Gronert, K; Martinsson-Niskanen, T; Ravasi, S; Chiang, N; Serhan, C N

    2001-01-01

    Aspirin-triggered lipoxin A(4) (ATL, 15-epi-LXA(4)) and leukotriene D(4) (LTD(4)) possess opposing vascular actions mediated via receptors distinct from the LXA(4) receptor (ALX) that is involved in leukocyte trafficking. Here, we identified these receptors by nucleotide sequencing and demonstrate that LTD(4) receptor (CysLT(1)) is induced in human vascular endothelia by interleukin-1beta. Recombinant CysLT(1) receptor gave stereospecific binding with both [(3)H]-LTD(4) and a novel labeled mimetic of ATL ([(3)H]-ATLa) that was displaced with LTD(4) and ATLa ( approximately IC(50) 0.2 to 0.9 nmol/L), but not with a bioinactive ATL isomer. The clinically used CysLT(1) receptor antagonist, Singulair, showed a lower rank order for competition with [(3)H]-ATLa (IC(50) approximately 8.3 nmol/L). In contrast, LTD(4) was an ineffective competitive ligand for recombinant ALX receptor with [(3)H]-ATLa, and ATLa did not compete for [(3)H]-LTB(4) binding with recombinant LTB(4) receptor. Endogenous murine CysLT(1) receptors also gave specific [(3)H]-ATLa binding that was displaced with essentially equal affinity by LTD(4) or ATLa. Systemic ATLa proved to be a potent inhibitor (>50%) of CysLT(1)-mediated vascular leakage in murine skin (200 microg/kg) in addition to its ability to block polymorphonuclear leukocyte recruitment to dorsal air pouch (4 microg/kg). These results indicate that ATL and LTD(4) bind and compete with equal affinity at CysLT(1), providing a molecular basis for aspirin-triggered LXs serving as a local damper of both vascular CysLT(1) signals as well as ALX receptor-regulated polymorphonuclear leukocyte traffic.

  8. Embarrassment: its distinct form and appeasement functions.

    Science.gov (United States)

    Keltner, D; Buswell, B N

    1997-11-01

    The authors address 2 questions about embarrassment. First, Is embarrassment a distinct emotion? The evidence indicates that the antecedents, experience, and display of embarrassment, and to a limited extent its autonomic physiology, are distinct from shame, guilt, and amusement and share the dynamic, temporal characteristics of emotion. Second, What are the theoretical accounts of embarrassment? Three accounts focus on the causes of embarrassment, positioning that it follows the loss of self-esteem, concern for others' evaluations, or absence of scripts to guide interactions. A fourth account focuses on the effects of the remedial actions of embarrassment, which correct preceding transgressions. A fifth account focuses on the functional parallels between embarrassment and nonhuman appeasement. The discussion focuses on unanswered questions about embarrassment.

  9. Distinctive skeletal dysplasia in Cockayne syndrome

    International Nuclear Information System (INIS)

    Silengo, M.C.; Franceschini, P.; Bianco, R.; Biagioli, M.; Pastorin, L.; Vista, N.; Baldassar, A.; Benso, L.

    1986-01-01

    Cockayne syndrom is a well-known autosomal recessive form of dwarfism with senile-like appearance. Skeletal changes such as flattening of vertebral bodies, ivory epiphyses and thickening of cranial vault, have been observed in some patients with this condition. We describe here a 5.5-year-old girl with the typical clinical signs of Cockayne syndrome and a distinctive form of bone dysplasia with major involvment of the spine. (orig.)

  10. Distinctive skeletal dysplasia in Cockayne syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Silengo, M.C.; Franceschini, P.; Bianco, R.; Biagioli, M.; Pastorin, L.; Vista, N.; Baldassar, A.; Benso, L.

    1986-03-01

    Cockayne syndrome is a well-known autosomal recessive form of dwarfism with senile-like appearance. Skeletal changes such as flattening of vertebral bodies, ivory epiphyses and thickening of cranial vault, have been observed in some patients with this condition. We describe here a 5.5-year-old girl with the typical clinical signs of Cockayne syndrome and a distinctive form of bone dysplasia with major involvement of the spine.

  11. Army nurses in wartime: distinction and pride.

    Science.gov (United States)

    Higgins, L P

    1996-08-01

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

  12. Theoretical energy level spectra and transition data for 4p64d, 4p64f and 4p54d2 configurations of W37+ ion

    International Nuclear Information System (INIS)

    Bogdanovich, P.; Kisielius, R.

    2012-01-01

    The ab initio quasirelativistic Hartree–Fock method developed specifically for the calculation of spectral parameters of heavy atoms and highly charged ions was applied to determine atomic data for tungsten ions. The correlation effects were included by adopting the configuration interaction method. The Breit–Pauli approximation for quasirelativistic Hartree–Fock radial orbitals was employed to take into account relativistic effects. The energy level spectra, radiative lifetimes, Lande factors g were calculated for the 4p 6 4d, 4p 6 4f and 4p 5 4d 2 configurations of W 37+ ion. The atomic data, namely, the transition wavelengths, spontaneous emission rates and oscillator strengths for the electric dipole, electric quadrupole and magnetic dipole transitions among and within the levels of these configurations are tabulated.

  13. Proper development of relay somatic sensory neurons and D2/D4 interneurons requires homeobox genes Rnx/Tlx-3 and Tlx-1.

    Science.gov (United States)

    Qian, Ying; Shirasawa, Senji; Chen, Chih-Li; Cheng, Leping; Ma, Qiufu

    2002-05-15

    Trigeminal nuclei and the dorsal spinal cord are first-order relay stations for processing somatic sensory information such as touch, pain, and temperature. The origins and development of these neurons are poorly understood. Here we show that relay somatic sensory neurons and D2/D4 dorsal interneurons likely derive from Mash1-positive neural precursors, and depend on two related homeobox genes, Rnx and Tlx-1, for proper formation. Rnx and Tlx-1 maintain expression of Drg11, a homeobox gene critical for the development of pain circuitry, and are essential for the ingrowth of trkA+ nociceptive/thermoceptive sensory afferents to their central targets. We showed previously that Rnx is necessary for proper formation of the nucleus of solitary tract, the target for visceral sensory afferents. Together, our studies demonstrate a central role for Rnx and Tlx-1 in the development of two major classes of relay sensory neurons, somatic and visceral.

  14. PREP-PWR-1.0: a WIMS-D/4 pre-processor code for the generation of data for PWR fuel assemblies

    International Nuclear Information System (INIS)

    Ball, G.

    1991-06-01

    The PREP-PWR-1.0 computer code is a substantially modified version of the PREWIM code which formed part of the original MARIA System (Report J.E.N. 543). PREP-PWR-1.0 is a comprehensive pre-processor code which generates input data for the WIMS-D/4.1 code (Report PEL 294) for PWR fuel assemblies, with or without control and burnable poison rods. This data is generated at various base and off-base conditions. The overall cross section generation methodology is described, followed by a brief overview of the model. Aspects of the base/off-base calculational scheme are outlined. Additional features of the code are described while the input data format of PREP-PWR-1.0 is listed. The sample problems and suggestions for further improvements to the code are also described. 2 figs., 2 tabs., 12 refs

  15. Self-diffusion and molecular association of acetylsalicylic acid and methyl salicylate in methanol- d4 in the temperature range 278-318 K

    Science.gov (United States)

    Golubev, V. A.; Kumeev, R. S.; Gurina, D. L.; Nikiforov, M. Yu.

    2017-05-01

    The effect of concentration on the self-diffusion coefficients of acetylsalicylic acid and methyl salicylate in methanol- d4 is investigated in the temperature range of 278-318 K using NMR. It is found that the self-diffusion coefficients increase along with temperature and fall as concentration rises. Within the limit of an infinitely dilute solution, the effective radii of solute molecules, calculated using the Stokes-Einstein equation shrink as the temperature grows. It is shown that the observed reduction of effective radii is associated with an increase in the fraction of solute monomers as the temperature rises. The physicochemical parameters of heteroassociation of acetylsalicylic acid and methyl salicylate with methanol are determined.

  16. Laboratory Study of the OH + Permethylsiloxane (L2, L3, D3, and D4) Reaction Rate Coefficients Between 240 and 370 K

    Science.gov (United States)

    Burkholder, J. B.; Bernard, F.; Papadimitriou, V. C.

    2016-12-01

    The atmospheric chemistry of organosiloxanes has recently been implicated in the formation of new particles as well as regional and indoor air quality. Methylsiloxanes with Sitextiles, health care and household products and in industrial applications as solvents and lubricants. They are released into the atmosphere during manufacturing, use, and disposal and have been observed in the atmosphere in ppb levels in certain locations. However, the fundamental chemical properties of this class of compounds, particularly their reactivity with the OH radical, are presently not fully characterized. In this work, the temperature dependence of the rate coefficients for the OH radical reaction with the simplest linear (L2 and L3) and cyclic (D3 and D4) siloxanes were measured: OH + (CH3)3SiOSi(CH3)3 = Products L2OH + [(CH3)3SiO]2Si(CH3)2 = Products L3OH + [-Si(CH3)2O-]3 = Products D3OH + [-Si(CH3)2O-]4 = Products D4OH rate coefficients were measured under pseudo-first conditions in OH over the temperature range 240-370 K using a pulsed laser photolysis-laser induced fluorescence (PLP-LIF) technique and at 296 K using a relative rate method. The present results are compared with available literature data where possible and discrepancies are discussed. The results from this work will be discussed in terms of the atmospheric lifetimes of these methylsiloxanes and the reactivity trends for this class of compound.

  17. Putative therapeutic targets for symptom subtypes of adult ADHD: D4 receptor agonism and COMT inhibition improve attention and response inhibition in a novel translational animal model.

    Science.gov (United States)

    Tomlinson, Anneka; Grayson, Ben; Marsh, Samuel; Hayward, Andrew; Marshall, Kay M; Neill, Joanna C

    2015-04-01

    Prefrontal cortical dopamine plays an important role in cognitive control, specifically in attention and response inhibition; the core deficits in ADHD. We have previously shown that methylphenidate and atomoxetine differentially improve these deficits dependent on baseline performance. The present study extends this work to investigate the effects of putative therapeutic targets in our model. A selective dopamine D4 receptor agonist (A-412997) and the catechol-O-methyl-transferase (COMT) inhibitor; tolcapone, were investigated in the combined subtype of adult ADHD (ADHD-C). Adult female rats were trained to criterion in the 5C-CPT (5-Choice Continuous Performance Task) and then separated into subgroups according to baseline levels of sustained attention, vigilance, and response disinhibition. The subgroups included: high-attentive (HA) and low-attentive with high response disinhibition (ADHD-C). The ADHD-C subgroup was selected to represent the combined subtype of adult ADHD. Effects of tolcapone (3.0, 10.0, 15.0mg/kg) and A-412997 (0.1, 0.3, 1.0µmol/kg) were tested by increasing the variable inter-trial-interval (ITI) duration in the 5C-CPT. Tolcapone (15mg/kg) significantly increased sustained attention, vigilance and response inhibition in ADHD-C animals, and impaired attention in HA animals. A-412997 (1.0µmol/kg) significantly increased vigilance and response inhibition in ADHD-C animals only, with no effect in HA animals. This is the first study to use the translational 5C-CPT to model the adult ADHD-C subtype in rats and to study new targets in this model. Both tolcapone and A-412997 increased vigilance and response inhibition in the ADHD-C subgroup. D4 and COMT are emerging as important potential therapeutic targets in adult ADHD that warrant further investigation. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  18. Free radicals in dicarboxylic acids: an e.s.r. study of radical conversions in γ-irradiated single crystals of glutaric acid and glutaric-2,2,4,4-d4 acid

    International Nuclear Information System (INIS)

    Bergene, R.; Minegishi, A.; Riesz, P.

    1980-01-01

    The γ-radiation-induced free radicals in single crystals of glutaric acid and glutaric-2,2,4,4-d 4 acid were studied in the temperature range 77-300 K by e.s.r. techniques. At 77 K the decarboxylation radical and the anion are stabilized. At higher temperatures the decarboxylation radical is found to be converted into a hydrogen abstraction radical with an activation energy of 6.3 +- 0.5 kcal/mole for the non-deuterated crystal. This radical is stable at room temperature. The anion seems to be converted to a unidentified intermediate radical which in turn is converted to the σ-acyl radical. An analysis of the g-value anisotropy and of the 13 C hyperfine splitting variation for this radical in the deuterated crystal is consistent with the assigned radical structure. By heat treatment the σ-acyl radical is converted to another form of the hydrogen abstraction radical with an activation energy of 9.6 +- 0.6 kcal/mole in the deuterated crystal. U.V.-light (lambda= 254 nm) transforms one of the room temperature radicals into the other. (author)

  19. Approaching the Distinction between Intuition and Insight.