835 research outputs found

    A Mutation in Amino Acid Permease AAP6 Reduces the Amino Acid Content of the Arabidopsis Sieve Elements but Leaves Aphid Herbivores Unaffected.

    Get PDF
    The aim of this study was to investigate the role of the amino acid permease gene AAP6 in regulating phloem amino acid composition and then to determine the effects of this altered diet on aphid performance. A genotype of Arabidopsis thaliana (L.) was produced in which the function of the amino acid permease gene AAP6 (At5g49630) was abolished. Plants homozygous for the insertionally inactivated AAP6 gene had a significantly larger mean rosette width than the wild type and a greater number of cauline leaves. Seeds from the aap6 mutant were also significantly larger than those from the wild-type plants. Sieve element (SE) sap was collected by aphid stylectomy and the amino acids derivatized, separated, and quantified using Capillary Electrophoresis with Laser Induced Fluorescence (CE-LIF). In spite of the large variation across samples, the total amino acid concentration of SE sap of the aap6 mutant plants was significantly lower than that of the wild-type plants. The concentrations of lysine, phenylalanine, leucine, and aspartic acid were all significantly lower in concentration in the aap6 mutant plants compared with wild-type plants. This is the first direct demonstration of a physiological role for an amino acid transporter in regulating SE composition in vivo. The amino acid availability in sieve element sap is thought to be the major limiting factor for aphid growth and reproduction. Despite the changes in their diet, the aphid Myzus persicae(Sulzer) displayed only small changes in feeding behaviour on mutant plants when measured using the Electronic Penetration Graph (EPG) technique. Salivation by the aphid into the SE (E1 phase) was increased on mutant plants but there was no significant effect on other feeding EPG behaviours, or in the rate of honeydew production. Consistent with the small effect on aphid feeding behaviour, there was only a small effect of reduced sieve element amino acid concentration on aphid reproduction. The data are discussed in relation to the regulation of phloem composition and the role of phloem amino acids in regulating aphid performance

    Someone is pulling the strings: hypersensitive agency detection and belief in conspiracy theories

    Get PDF
    We hypothesized that belief in conspiracy theories would be predicted by the general tendency to attribute agency and intentionality where it is unlikely to exist. We further hypothesized that this tendency would explain the relationship between education level and belief in conspiracy theories, where lower levels of education have been found to be associated with higher conspiracy belief. In Study 1 (N=202) participants were more likely to agree with a range of conspiracy theories if they also tended to attribute intentionality and agency to inanimate objects. As predicted, this relationship accounted for the link between education level and belief in conspiracy theories. We replicated this finding in Study 2 (N=330), whilst taking into account beliefs in paranormal phenomena. These results suggest that education may undermine the reasoning processes and assumptions that are reflected in conspiracy belief

    Coordination of glioblastoma cell motility by PKCĪ¹

    Get PDF
    Abstract Background Glioblastoma is one of the deadliest forms of cancer, in part because of its highly invasive nature. The tumor suppressor PTEN is frequently mutated in glioblastoma and is known to contribute to the invasive phenotype. However the downstream events that promote invasion are not fully understood. PTEN loss leads to activation of the atypical protein kinase C, PKCĪ¹. We have previously shown that PKCĪ¹ is required for glioblastoma cell invasion, primarily by enhancing cell motility. Here we have used time-lapse videomicroscopy to more precisely define the role of PKCĪ¹ in glioblastoma. Results Glioblastoma cells in which PKCĪ¹ was either depleted by shRNA or inhibited pharmacologically were unable to coordinate the formation of a single leading edge lamellipod. Instead, some cells generated multiple small, short-lived protrusions while others generated a diffuse leading edge that formed around the entire circumference of the cell. Confocal microscopy showed that this behavior was associated with altered behavior of the cytoskeletal protein Lgl, which is known to be inactivated by PKCĪ¹ phosphorylation. Lgl in control cells localized to the lamellipod leading edge and did not associate with its binding partner non-muscle myosin II, consistent with it being in an inactive state. In PKCĪ¹-depleted cells, Lgl was concentrated at multiple sites at the periphery of the cell and remained in association with non-muscle myosin II. Videomicroscopy also identified a novel role for PKCĪ¹ in the cell cycle. Cells in which PKCĪ¹ was either depleted by shRNA or inhibited pharmacologically entered mitosis normally, but showed marked delays in completing mitosis. Conclusions PKCĪ¹ promotes glioblastoma motility by coordinating the formation of a single leading edge lamellipod and has a role in remodeling the cytoskeleton at the lamellipod leading edge, promoting the dissociation of Lgl from non-muscle myosin II. In addition PKCĪ¹ is required for the transition of glioblastoma cells through mitosis. PKCĪ¹ therefore has a role in both glioblastoma invasion and proliferation, two key aspects in the malignant nature of this disease

    A sedge plant as the source of Kangaroo Island propolis rich in prenylated p-coumarate ester and stilbenes

    Get PDF
    AbstractPropolis samples from Kangaroo Island, South Australia, were investigated for chemical constituents using high-field nuclear magnetic resonance spectral profiling. A type of propolis was found containing a high proportion of prenylated hydroxystilbenes. Subsequently, the botanical origin of this type of propolis was identified using a beehive propolis depletion method and analysis of flora. Ligurian honey bees, Apis mellifera ligustica Spinola, were found to produce propolis from resin exuded by the Australian native sedge plant Lepidosperma sp. Montebello (Cyperaceae). The plants, commonly known as sword sedge, were found to have resin that matched with the propolis samples identified as the most abundant propolis type on the island containing C- and O-prenylated tetrahydroxystilbenes (pTHOS) in addition to a small amount of prenylated p-coumarate. The isolation of five pTHOS not previously characterized are reported: (E)-4-(3-methyl-2-buten-1-yl)-3,4ā€²,5-trihydroxy-3ā€²-methoxystilbene, (E)-2,4-bis(3-methyl-2-buten-1-yl)-3,3ā€²,4ā€²,5-tetrahydroxystilbene, (E)-2-(3-methyl-2-buten-1-yl)-3-(3-methyl-2-butenyloxy)-3ā€²,4ā€²,5-trihydroxystilbene, (E)-2,6-bis(3-methyl-2-buten-1-yl)-3,3ā€²,5,5ā€²-tetrahydroxystilbene and (E)-2,6-bis(3-methyl-2-buten-1-yl)-3,4ā€²,5-trihydroxy-3ā€²-methoxystilbene. A National Cancer Institute 60 human cell line anticancer screen of three of these compounds showed growth inhibitory activity. The large Australasian genus Lepidosperma is identified as a valuable resource for the isolation of substances with medicinal potential

    The Role of Quantitative Pharmacology in an Academic Translational Research Environment

    Get PDF
    Translational research is generally described as the application of basic science discoveries to the treatment or prevention of disease or injury. Its value is usually determined based on the likelihood that exploratory or developmental research can yield effective therapies. While the pharmaceutical industry has evolved into a highly specialized sector engaged in translational research, the academic medical research community has similarly embraced this paradigm largely through the motivation of the National Institute of Health (NIH) via its Roadmap initiative. The Clinical and Translational Science Award (CTSA) has created opportunities for institutions which can provide the multidisciplinary environment required to engage such research. A key component of the CTSA and an element of both the NIH Roadmap and the FDA Critical Path is the bridging of bench and bedside science via quantitative pharmacologic relationships. The infrastructure of the University of Pennsylvania/Childrenā€™s Hospital of Philadelphia CTSA is highlighted relative to both research and educational objectives reliant upon quantitative pharmacology. A case study, NIH-sponsored research program exploring NK1r antagonism for the treatment NeuroAIDS is used to illustrate the application of quantitative pharmacology in a translational research paradigm

    Critical Exponents, Hyperscaling and Universal Amplitude Ratios for Two- and Three-Dimensional Self-Avoiding Walks

    Get PDF
    We make a high-precision Monte Carlo study of two- and three-dimensional self-avoiding walks (SAWs) of length up to 80000 steps, using the pivot algorithm and the Karp-Luby algorithm. We study the critical exponents Ī½\nu and 2Ī”4āˆ’Ī³2\Delta_4 -\gamma as well as several universal amplitude ratios; in particular, we make an extremely sensitive test of the hyperscaling relation dĪ½=2Ī”4āˆ’Ī³d\nu = 2\Delta_4 -\gamma. In two dimensions, we confirm the predicted exponent Ī½=3/4\nu = 3/4 and the hyperscaling relation; we estimate the universal ratios Ā /Ā =0.14026Ā±0.00007\ / \ = 0.14026 \pm 0.00007, Ā /Ā =0.43961Ā±0.00034\ / \ = 0.43961 \pm 0.00034 and ĪØāˆ—=0.66296Ā±0.00043\Psi^* = 0.66296 \pm 0.00043 (68\% confidence limits). In three dimensions, we estimate Ī½=0.5877Ā±0.0006\nu = 0.5877 \pm 0.0006 with a correction-to-scaling exponent Ī”1=0.56Ā±0.03\Delta_1 = 0.56 \pm 0.03 (subjective 68\% confidence limits). This value for Ī½\nu agrees excellently with the field-theoretic renormalization-group prediction, but there is some discrepancy for Ī”1\Delta_1. Earlier Monte Carlo estimates of Ī½\nu, which were ā‰ˆā€‰ā£0.592\approx\! 0.592, are now seen to be biased by corrections to scaling. We estimate the universal ratios Ā /Ā =0.1599Ā±0.0002\ / \ = 0.1599 \pm 0.0002 and ĪØāˆ—=0.2471Ā±0.0003\Psi^* = 0.2471 \pm 0.0003; since ĪØāˆ—>0\Psi^* > 0, hyperscaling holds. The approach to ĪØāˆ—\Psi^* is from above, contrary to the prediction of the two-parameter renormalization-group theory. We critically reexamine this theory, and explain where the error lies.Comment: 87 pages including 12 figures, 1029558 bytes Postscript (NYU-TH-94/09/01

    Scaling of Star Polymers with one to 80 Arms

    Full text link
    We present large statistics simulations of 3-dimensional star polymers with up to f=80f=80 arms, and with up to 4000 monomers per arm for small values of ff. They were done for the Domb-Joyce model on the simple cubic lattice. This is a model with soft core exclusion which allows multiple occupancy of sites but punishes each same-site pair of monomers with a Boltzmann factor v<1v<1. We use this to allow all arms to be attached at the central site, and we use the `magic' value v=0.6v=0.6 to minimize corrections to scaling. The simulations are made with a very efficient chain growth algorithm with resampling, PERM, modified to allow simultaneous growth of all arms. This allows us to measure not only the swelling (as observed from the center-to-end distances), but also the partition sum. The latter gives very precise estimates of the critical exponents Ī³f\gamma_f. For completeness we made also extensive simulations of linear (unbranched) polymers which give the best estimates for the exponent Ī³\gamma.Comment: 7 pages, 7 figure

    Integrated multi-level quality control for proteomic profiling studies using mass spectrometry

    Get PDF
    BACKGROUND: Proteomic profiling using mass spectrometry (MS) is one of the most promising methods for the analysis of complex biological samples such as urine, serum and tissue for biomarker discovery. Such experiments are often conducted using MALDI-TOF (matrix-assisted laser desorption/ionisation time-of-flight) and SELDI-TOF (surface-enhanced laser desorption/ionisation time-of-flight) MS. Using such profiling methods it is possible to identify changes in protein expression that differentiate disease states and individual proteins or patterns that may be useful as potential biomarkers. However, the incorporation of quality control (QC) processes that allow the identification of low quality spectra reliably and hence allow the removal of such data before further analysis is often overlooked. In this paper we describe rigorous methods for the assessment of quality of spectral data. These procedures are presented in a user-friendly, web-based program. The data obtained post-QC is then examined using variance components analysis to quantify the amount of variance due to some of the factors in the experimental design. RESULTS: Using data from a SELDI profiling study of serum from patients with different levels of renal function, we show how the algorithms described in this paper may be used to detect systematic variability within and between sample replicates, pooled samples and SELDI chips and spots. Manual inspection of those spectral data that were identified as being of poor quality confirmed the efficacy of the algorithms. Variance components analysis demonstrated the relatively small amount of technical variance attributable to day of profile generation and experimental array. CONCLUSION: Using the techniques described in this paper it is possible to reliably detect poor quality data within proteomic profiling experiments undertaken by MS. The removal of these spectra at the initial stages of the analysis substantially improves the confidence of putative biomarker identification and allows inter-experimental comparisons to be carried out with greater confidence

    NCBI Peptidome: a new repository for mass spectrometry proteomics data

    Get PDF
    Peptidome is a public repository that archives and freely distributes tandem mass spectrometry peptide and protein identification data generated by the scientific community. Data from all stages of a mass spectrometry experiment are captured, including original mass spectra files, experimental metadata and conclusion-level results. The submission process is facilitated through acceptance of data in commonly used open formats, and all submissions undergo syntactic validation and curation in an effort to uphold data integrity and quality. Peptidome is not restricted to specific organisms, instruments or experiment types; data from any tandem mass spectrometry experiment from any species are accepted. In addition to data storage, web-based interfaces are available to help users query, browse and explore individual peptides, proteins or entire Samples and Studies. Results are integrated and linked with other NCBI resources to ensure dissemination of the information beyond the mass spectroscopy proteomics community. Peptidome is freely accessible at http://www.ncbi.nlm.nih.gov/peptidome
    • ā€¦
    corecore