14 research outputs found

    Wave propagation and tunneling through periodic structures

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    The phenomenon of tunneling manifests itself in nearly every field of physics. The ability to distinguish a wave tunneling through a barrier from one propagating is important for a number of applications. Here we explore the properties of the wave traveling through the band gap created by a lattice, either as a consequence of tunneling through the barrier or due to the presence of a pass band inside the gap. To observe the pass band for studying tunneling and propagating waves simultaneously, a localized lattice defect was introduced. The differences between the two phenomena are highlighted via waves' dispersion characteristics

    Zebrafish Models of Cancer

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    A zebrafish model of dyskeratosis congenita reveals hematopoietic stem cell formation failure resulting from ribosomal protein-mediated p53 stabilization

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    Dyskeratosis congenita (DC) is a bone marrow failure disorder characterized by shortened telomeres, defective stem cell maintenance, and highly heterogeneous phenotypes affecting predominantly tissues that require high rates of turnover. Here we present a mutant zebrafish line with decreased expression of nop10, one of the known H/ACA RNP complex genes with mutations linked to DC. We demonstrate that this nop10 loss results in 18S rRNA processing defects and collapse of the small ribosomal subunit, coupled to stabilization of the p53 tumor suppressor protein through small ribosomal proteins binding to Mdm2. These mutants also display a hematopoietic stem cell deficiency that is reversible on loss of p53 function. However, we detect no changes in telomere length in nop10 mutants. Our data support a model of DC whereupon in early development mutations involved in the H/ACA complex contribute to bone marrow failure through p53 deregulation and loss of initial stem cell numbers while their role in telomere maintenance does not contribute to DC until later in life.

    Extensive localization of long noncoding RNAs to the cytosol and mono- and polyribosomal complexes

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    Contains fulltext : 138006.pdf (publisher's version ) (Open Access)BACKGROUND: Long noncoding RNAs (lncRNAs) form an abundant class of transcripts, but the function of the majority of them remains elusive. While it has been shown that some lncRNAs are bound by ribosomes, it has also been convincingly demonstrated that these transcripts do not code for proteins. To obtain a comprehensive understanding of the extent to which lncRNAs bind ribosomes, we performed systematic RNA sequencing on ribosome-associated RNA pools obtained through ribosomal fractionation and compared the RNA content with nuclear and (non-ribosome bound) cytosolic RNA pools. Results : The RNA composition of the subcellular fractions differs significantly from each other, but lncRNAs are found in all locations. A subset of specific lncRNAs is enriched in the nucleus but surprisingly the majority is enriched in the cytosol and in ribosomal fractions. The ribosomal enriched lncRNAs include H19 and TUG1. CONCLUSIONS: Most studies on lncRNAs have focused on the regulatory function of these transcripts in the nucleus. We demonstrate that only a minority of all lncRNAs are nuclear enriched. Our findings suggest that many lncRNAs may have a function in cytoplasmic processes, and in particular in ribosome complexes

    Free-electron maser based on a cavity with two- and one-dimensional distributed feedback

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    The study of a coaxial free-electron maser (FEM) based on two-dimensional (2D) and one-dimensional (1D) distributed feedback, driven by a 70 mm diameter, annular electron beam is presented. A new cavity formed with 2D and 1D periodic lattices, positioned at the input and output of the interaction region, respectively, was used. It has been demonstrated that 2D distributed feedback in the input mirror allowed 8 mm radiation emitted from different parts of the electron beam to be synchronized. The FEM operating in the 35.9-38.9 GHz frequency region generated 65 MW, 150 ns duration millimetre wave pulses which contained ∼ 10 J of energy in the pulse

    The nucleolar GTP-binding proteins Gnl2 and nucleostemin are required for retinal neurogenesis in developing zebrafish

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    Nucleostemin (NS), a member of a family of nucleolar GTP-binding proteins, is highly expressed in proliferating cells such as stem and cancer cells and is involved in the control of cell cycle progression. Both depletion and overexpression of NS result in stabilization of the tumor suppressor p53 protein in vitro. Although it has been previously suggested that NS has p53-independent functions, these to date remain unknown. Here, we report two zebrafish mutants recovered from forward and reverse genetic screens that carry loss of function mutations in two members of this nucleolar protein family, Guanine nucleotide binding-protein-like 2 (Gnl2) and Gnl3/NS. We demonstrate that these proteins are required for correct timing of cell cycle exit and subsequent neural differentiation in the brain and retina. Concomitantly, we observe aberrant expression of the cell cycle regulators cyclinD1 and p57kip2. Our models demonstrate that the loss of Gnl2 or NS induces p53 stabilization and p53-mediated apoptosis. However, the retinal differentiation defects are independent of p53 activation. Furthermore, this work demonstrates that Gnl2 and NS have both non-cell autonomously and cell-autonomous function in correct timing of cell cycle exit and neural differentiation. Finally, the data suggest that Gnl2 and NS affect cell cycle exit of neural progenitors by regulating the expression of cell cycle regulators independently of p53. [KEYWORDS: Animals, Blotting, Western, Bromodeoxyuridine, Cell Cycle/ physiology, Cyclin D1/metabolism, Cyclin-Dependent Kinase Inhibitor p57/metabolism, GTP-Binding Proteins/genetics/ metabolism, Gene Expression Regulation/ physiology, Immunohistochemistry, In Situ Hybridization, Microarray Analysis, Microscopy, Fluorescence, Mutation/genetics, Neurogenesis/ physiology, Nuclear Proteins/genetics/ metabolism, Oligonucleotides/genetics, Plasmids/genetics, Retina/ embryology, Zebrafish/ embryolog

    Perinatal exogenous nitric oxide in fawn-hooded hypertensive rats reduces renal ribosomal biogenesis in early life

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    Nitric oxide (NO) is known to depress ribosome biogenesis in vitro. In this study we analyzed the influence of exogenous NO on ribosome biogenesis in vivo using a proven antihypertensive model of perinatal NO administration in genetically hypertensive rats. Fawn-hooded hypertensive rat (FHH) dams were supplied with the NO-donor molsidomine in drinking water from 2 weeks before to 4 weeks after birth, and the kidneys were subsequently collected from 2 day, 2 week, and 9 to 10-month-old adult offspring. Although the NO-donor increased maternal NO metabolite excretion, the NO status of juvenile renal (and liver) tissue was unchanged as assayed by EPR spectroscopy of NO trapped with iron-dithiocarbamate complexes. Nevertheless, microarray analysis revealed marked differential up-regulation of renal ribosomal protein genes at 2 days and down-regulation at 2 weeks and in adult males. Such differential regulation of renal ribosomal protein genes was not observed in females. These changes were confirmed in males at 2 weeks by expression analysis of renal ribosomal protein L36a and by polysome profiling, which also revealed a down-regulation of ribosomes in females at that age. However, renal polysome profiles returned to normal in adults after early exposure to molsidomine. No direct effects of molsidomine were observed on cellular proliferation in kidneys at any age, and the changes induced by molsidomine in renal polysome profiles at 2 weeks were absent in the livers of the same rats. Our results suggest that the previously found prolonged antihypertensive effects of perinatal NO administration may be due to epigenetically programmed alterations in renal ribosome biogenesis during a critical fetal period of renal development, and provide a salient example of a drug-induced reduction of ribosome biogenesis that is accompanied by a beneficial long-term health effect in both males and females. Keywords: nitric oxide, ribosomal biogenesis, microarray, polysome profiling, perinatal, epigenetic, kidne

    Free-electron maser based on two-dimensional distributed feedback

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    The study of a co-axial free-electron maser (FEM) based on 2D and ID distributed feedback and driven by a large diameter (70 mm), annular electron beam is presented. It has been demonstrated that 2D distributed feedback in the input mirror allowed 8 mm radiation emitted from different parts of the oversized electron beam to be synchronized. The FEM operating in the (35.9 GHz to 38.9 GHz.) frequency region generated 60 MW, 150 ns duration millimetre wave pulses which contained ~9 J of energy in the pulse. Good agreement between theoretical predictions and experimental data is demonstrated

    Insulin/IGF-1-mediated longevity is marked by reduced protein metabolism

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    Mutations in the daf-2 gene of the conserved Insulin/Insulin-like Growth Factor (IGF-1) pathway double the lifespan of the nematode Caenorhabditis elegans. This phenotype is completely suppressed by deletion of Forkhead transcription factor daf-16. To uncover regulatory mechanisms coordinating this extension of life, we employed a quantitative proteomics strategy with daf-2 mutants in comparison with N2 and daf-16; daf-2 double mutants. This revealed a remarkable longevity-specific decrease in proteins involved in mRNA processing and transport, the translational machinery, and protein metabolism. Correspondingly, the daf-2 mutants display lower amounts of mRNA and 20S proteasome activity, despite maintaining total protein levels equal to that observed in wild types. Polyribosome profiling in the daf-2 and daf-16;daf-2 double mutants confirmed a daf-16-dependent reduction in overall translation, a phenotype reminiscent of Dietary Restriction-mediated longevity, which was independent of germline activity. RNA interference (RNAi)-mediated knockdown of proteins identified by our approach resulted in modified C. elegans lifespan confirming the importance of these processes in Insulin/IGF-1-mediated longevity. Together, the results demonstrate a role for the metabolism of proteins in the Insulin/IGF-1-mediated extension of life

    Progress and plans for nonlinear wave-plasma interaction experiments

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    An electromagnetic wave employed to introduce energy into plasma non-linearly exchanges energy via complex interactions with particles and plasma wave modes. Examples include Raman scattering where two electromagnetic waves are coupled via a Langmuir wave and Brillouin scattering where the coupling is via an ion-acoustic wave. One electromagnetic wave may be externally driven with the secondary electromagnetic wave growing naturally or both electromagnetic waves may be driven. Where beat-waves are coupled to the electron and ion cyclotron motions or hybrid oscillations, multi-wave interactions may be useful to drive current or heat the plasma in magnetically confined fusion. The paper presents progress on the design, objectives and numerical simulations of a cylindrical plasma apparatus, 1 m diameter and 3 m length for multifrequency microwave interaction experiments in plasmas. An RF source driving a flat spiral antenna will be used to ionize either an unmagnetised plasma by inductive coupling or a magnetised plasma (Te~ few eV, ne in the range 1015 – 1018 m-3 ) by helicon wave [1] injection. The magnetic field can reach up to 0.085 T. Diagnostics include line-integrated microwave interferometers and translatable probes to measure Te, ne, and fluctuations excited by the electromagnetic waves. Undertaking these experiments at microwave frequencies will grant enhanced active control of the injected waves and diagnostics. Combining measurement, simulation and theoretical analysis an enhanced understanding of the physics of these interactions for fusion relevant plasmas and for laser-plasma interactions is anticipated. The project builds on previous research in magnetospheric cyclotron instabilities [2-4]. This authors gratefully acknowledge support from the UKEPSRC through grants EP/R004773/1 and EP/R034737/1
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