434 research outputs found

    Rotatin is a novel gene required for axial rotation and left- right specification in mouse embryos

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    The genetic cascade that governs left-right (L-R) specification is starting to be elucidated. In the mouse, the lateral asymmetry of the body axis is revealed first by the asymmetric expression of nodal, lefry2 and pitx2 in the left lateral plate mesoderm of the neurulating embryo. Here we describe a novel gene, rotatin, essential for the correct expression of the key L-R specification genes nodal, lefty and Pitx2. Embryos deficient in rotatin show also randomized heart looping and delayed neural tube closure, and fail to undergo the critical morphogenetic step of axial rotation. The amino acid sequence deduced from the cDNA is predicted to contain at least three transmembrane domains. Our results show a novel key player in the genetic cascade that determines L-R specification, and suggest a causal link between this process and axial rotation. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved

    “Not in the mood”: The fear of being laughed at is better predicted by humor temperament traits than diagnosis in neurodevelopmental conditions

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    BACKGROUND: Research has shown that autistic individuals seem to be more prone to develop gelotophobia (i.e., the fear of being laughed at) than typically developing individuals. The goals of the present study were to discover whether the high levels of gelotophobia found in autism in previous studies were replicated here, to expand the research to Down syndrome (DS) and Williams syndrome (WS), and to assess the relation between individual differences and social impairments, affective predispositions, and humor temperament. METHODS: Questionnaires were distributed to parents of autistic individuals (N = 48), individuals with DS (N = 139), and individuals with WS (N = 43) aged between 5 and 25 years old. RESULTS: Autistic individuals were shown to frequently experience at least a slight level of gelotophobia (45%), compared to only 6% of individuals with DS and 7% of individuals with WS. Interestingly, humorless temperament traits (i.e., seriousness and bad mood) manifested as the strongest predictors of gelotophobia. This relation even transcended group differences. CONCLUSION: The results confirm that gelotophobia seems to be particularly concerning for autistic individuals, whereas individuals with DS and WS seem to be more protected from developing such a fear. Moreover, it appears that gelotophobia seems to be more linked to high seriousness and irritability than diagnosis

    Dicarbon­yl(η5-cyclo­penta­dien­yl)bis­(trimethyl­phosphine)molybdenum(II) trifluoro­methane­sulfonate

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    In the title compound, [Mo(C5H5)(CO)2(C3H9P)2]CF3SO3, the cationic complex displays a classical four-legged piano-stool square-pyramidal geometry with a trans configuration of the basal ligands around the Mo atom. The cyclo­penta­dienyl (Cp) ligand occupies the apical position of the piano-stool configuration. The average Mo—P bond length of the two trans PMe3 ligands is 2.474 (5) Å and the Mo—Cp centroid distance is 2.003 (2) Å

    Transcription factors Sp1 and Sp4 regulate TRPV1 gene expression in rat sensory neurons

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    <p>Abstract</p> <p>Background</p> <p>The capsaicin receptor, transient receptor potential vanilloid type -1 (TRPV1) directs complex roles in signal transduction including the detection of noxious stimuli arising from cellular injury and inflammation. Under pathophysiologic conditions, TRPV1 mRNA and receptor protein expression are elevated in dorsal root ganglion (DRG) neurons for weeks to months and is associated with hyperalgesia. Building on our previous isolation of a promoter system for the rat TRPV1 gene, we investigated the proximal TRPV1 P2-promoter by first identifying candidate Sp1-like transcription factors bound <it>in vivo </it>to the P2-promoter using chromatin immunoprecipitation (ChIP) assay. We then performed deletion analysis of GC-box binding sites, and quantified promoter activity under conditions of Sp1 / Sp4 over-expression versus inhibition/knockdown. mRNA encoding Sp1, Sp4 and TRPV1 were quantified by qRT-PCR under conditions of Sp1/Sp4 over-expression or siRNA mediated knockdown in cultured DRG neurons.</p> <p>Results</p> <p>Using ChIP analysis of DRG tissue, we demonstrated that Sp1 and Sp4 are bound to the candidate GC-box site region within the endogenous TRPV1 P2-promoter. Deletion of GC-box "a" or "a + b" within the P2- promoter resulted in a complete loss of transcriptional activity indicating that GC-box "a" was the critical site for promoter activation. Co-transfection of Sp1 increased P2-promoter activity in cultured DRG neurons whereas mithramycin-a, an inhibitor of Sp1-like function, dose dependently blocked NGF and Sp1-dependent promoter activity in PC12 cells. Co-transfection of siRNA directed against Sp1 or Sp4 decreased promoter activity in DRG neurons and NGF treated PC12 cells. Finally, electroporation of Sp1 or Sp4 cDNA into cultures of DRG neurons directed an increase in Sp1/Sp4 mRNA and importantly an increase in TRPV1 mRNA. Conversely, combined si-RNA directed knockdown of Sp1/Sp4 resulted in a decrease in TRPV1 mRNA.</p> <p>Conclusion</p> <p>Based on these studies, we now propose a model of TRPV1 expression that is dependent on Sp1-like transcription factors with Sp4 playing a predominant role in activating TRPV1 RNA transcription in DRG neurons. Given that increases of TRPV1 expression have been implicated in a wide range of pathophysiologic states including persistent painful conditions, blockade of Sp1-like transcription factors represents a novel direction in therapeutic strategies.</p

    Economic impact to shipping industry : Economic impact to shipping industry considering Maritime Spatial Planning and green routes in pilot case studies

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    In this project, three case studies are considered in order to examine the economic impact of the implementation of MSP when considering environmental impact of the shipping industry. Specific characteristics and limitations of areas in the Greek Sea, the Balearic Sea and the Baltic Sea are evaluated with respect to their economic effects on the maritime transport domain. The purpose of the above is to evaluate the economic impacts and risk implications of different scenarios and particularly: The economic impact of vessel traffic rerouting and/or reducing the speed in order to reduce the probability of vessel strikes or other negative impact to endangered marine species. Analysis and treatment of costs (constraints and penalties) from unexpected delays, in addition to the additional transit time cost. Estimation of the direct and indirect economic impact on the shipping industry and the effects of potential port call dislocation for the implementation of the proposed management options (e.g. speed deceleration or ship rerouting).https://commons.wmu.se/monalisa2/1001/thumbnail.jp

    A method of estimation of the dynamical age of FR II-type radio sources from multifrequency data

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    We propose a new approach in determining ages of FR II type radio sources. We apply the assumed dynamical model of Kaiser et al. (1997) to a number of FR II type radio galaxies observed at different radio frequencies, and fit - for each frequency separately - the model free parameters to the observed sources' quantities. Such a procedure, using enlarged in fact a number of observables, enables us to determine relatively precise ages and other crucial characteristics of the analyzed sources. The resulting age estimates agree very well with those obtained by means of `classical' spectral ageing method for objects not older than 10 Myr, for which good-quality spectral data are available. The presented method is however also applicable in the case of the sources older than this, and/or the ones for which the only available low-resolution radio data do not allow for detailed spectral ageing studies. Our analysis indicates that the main factor precluding precise age determination for FR II type radio galaxies regards the poorly known shape of the initial electron energy distribution injected by the jet terminal shocks to the expanding lobes/cocoons. We briefly consider this issue, and conclude that the broad-band single power-law form assumed here may be accurate enough for the presented estimates, although most likely it does not strictly correspond to some well-defined realistic particle acceleration process. Instead, it should be considered as a simplest model approximation of the initial electron continuum, averaged over a very broad energy range and over the age of the source, with the effective spectral index which may be different for different sources.Comment: 15 pages, 9 figures included. Accepted for publication in A&

    A conserved function of the zinc finger transcription factor Sp8/9 in allometric appendage growth in the milkweed bug Oncopeltus fasciatus

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    The genes encoding the closely related zinc finger transcription factors Buttonhead (Btd) and D-Sp1 are expressed in the developing limb primordia of Drosophila melanogaster and are required for normal growth of the legs. The D-Sp1 homolog of the red flour beetle Tribolium castaneum, Sp8 (appropriately termed Sp8/9), is also required for the proper growth of the leg segments. Here we report on the isolation and functional study of the Sp8/9 gene from the milkweed bug Oncopeltus fasciatus. We show that Sp8/9 is expressed in the developing appendages throughout development and that the downregulation of Sp8/9 via RNAi leads to antennae, rostrum, and legs with shortened and fused segments. This supports a conserved role of Sp8/9 in allometric leg segment growth. However, all leg segments including the claws are present and the expression of the leg genes Distal-less, dachshund, and homothorax are proportionally normal, thus providing no evidence for a role of Sp8/9 in appendage specification

    Final report on the search for neutrinoless double-β decay of 76Ge from the Gotthard underground experiment

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    We report here on the final results of a search for Ge-76 double-beta decay conducted in the Gotthard underground laboratory. The detector consists of an array of eight high-purity natural germanium crystals totaling 1095 cm^3 fiducial volume. The accumulated data set represents a sensitivity of 10.0 kg yr. No indication of neutrinoless double-beta decay was found. The measured half-life limits are T1/2(0+ --> 0+) > 6.0(3.3) x 10^(23) yr for the transition to the ground state and T1/2(0+ --> 2+) > 1.4(0.65) x 10^(23) yr for the transition to the first excited state at 68% (90%) C.L. From these results we derive an upper limit for the Majorana mass of the neutrino in the range of 1.8 to 6.7 eV depending on matrix-element calculations. The same results allow limits to be set for the right-handed-current parameters: < 2.2 x 10^(-8)

    Atmospheric Muon Flux at Sea Level, Underground, and Underwater

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    The vertical sea-level muon spectrum at energies above 1 GeV and the underground/underwater muon intensities at depths up to 18 km w.e. are calculated. The results are particularly collated with a great body of the ground-level, underground, and underwater muon data. In the hadron-cascade calculations, the growth with energy of inelastic cross sections and pion, kaon, and nucleon generation in pion-nucleus collisions are taken into account. For evaluating the prompt muon contribution to the muon flux, we apply two phenomenological approaches to the charm production problem: the recombination quark-parton model and the quark-gluon string model. To solve the muon transport equation at large depths of homogeneous medium, a semi-analytical method is used. The simple fitting formulas describing our numerical results are given. Our analysis shows that, at depths up to 6-7 km w. e., essentially all underground data on the muon intensity correlate with each other and with predicted depth-intensity relation for conventional muons to within 10%. However, the high-energy sea-level data as well as the data at large depths are contradictory and cannot be quantitatively decribed by a single nuclear-cascade model.Comment: 47 pages, REVTeX, 15 EPS figures included; recent experimental data and references added, typos correcte
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