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Sökning: WFRF:(Christodoulou John)

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1.
  • Blombach, Fabian, et al. (författare)
  • Archaeal MBF1 binds to 30S and 70S ribosomes via its helix-turn-helix domain
  • 2014
  • Ingår i: Biochemical Journal. - 0264-6021 .- 1470-8728. ; 462, s. 373-384
  • Tidskriftsartikel (refereegranskat)abstract
    • MBF1 (multi-protein bridging factor 1) is a protein containing a conserved HTH (helix-turn-helix) domain in both eukaryotes and archaea. Eukaryotic MBF1 has been reported to function as a transcriptional co-activator that physically bridges transcription regulators with the core transcription initiation machinery of RNA polymerase II. In addition, MBF1 has been found to be associated with polyadenylated mRNA in yeast as well as in mammalian cells. aMBF1 (archaeal MBF1) is very well conserved among most archaeal lineages; however, its function has so far remained elusive. To address this, we have conducted a molecular characterization of this aMBF1. Affinity purification of interacting proteins indicates that aMBF1 binds to ribosomal subunits. On sucrose density gradients, aMBF1 co-fractionates with free 30S ribosomal subunits as well as with 70S ribosomes engaged in translation. Binding of aMBF1 to ribosomes does not inhibit translation. Using NMR spectroscopy, we show that aMBF1 contains a long intrinsically disordered linker connecting the predicted N-terminal zinc-ribbon domain with the C-terminal HTH domain. The HTH domain, which is conserved in all archaeal and eukaryotic MBF1 homologues, is directly involved in the association of aMBF1 with ribosomes. The disordered linker of the ribosome-bound aMBF1 provides the N-terminal domain with high flexibility in the aMBF1 ribosome complex. Overall, our findings suggest a role for aMBF1 in the archaeal translation process.
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2.
  • Lenherr, Nina, et al. (författare)
  • Co-therapy with S-adenosylmethionine and nicotinamide riboside improves t-cell survival and function in Arts Syndrome (PRPS1 deficiency)
  • 2021
  • Ingår i: Molecular Genetics and Metabolism Reports. - : Elsevier. - 2214-4269. ; 26
  • Tidskriftsartikel (refereegranskat)abstract
    • Arts syndrome or phosphoribosyl-pyrophosphate-synthetase-1 (PRPS1) deficiency is caused by loss-of-function mutations in the PRPS1 gene (Xq22.3). PRPS1 is an initial and essential step for the synthesis of the nucleotides of purines, pyrimidines, and nicotinamide. Classically, affected males present with sensorineural hearing loss, optic atrophy, muscular hypotonia, developmental impairment, and recurrent severe respiratory infections early in life. Treatment of a 3-year old boy with S-adenosylmethionine (SAM) replenished erythrocyte purine nucleotides of adenosine and guanosine, while SAM and nicotinamide riboside co-therapy further improved his clinical phenotype as well as T-cell survival and function.
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  • Mehrtens, Nicola, et al. (författare)
  • The XMM Cluster Survey : optical analysis methodology and the first data release
  • 2012
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 423:2, s. 1024-1052
  • Tidskriftsartikel (refereegranskat)abstract
    • The XMM Cluster Survey (XCS) is a serendipitous search for galaxy clusters using all publicly available data in the XMMNewton Science Archive. Its main aims are to measure cosmological parameters and trace the evolution of X-ray scaling relations. In this paper we present the first data release from the XMM Cluster Survey (XCS-DR1). This consists of 503 optically confirmed, serendipitously detected, X-ray clusters. Of these clusters, 256 are new to the literature and 357 are new X-ray discoveries. We present 463 clusters with a redshift estimate (0.06 < z < 1.46), including 261 clusters with spectroscopic redshifts. The remainder have photometric redshifts. In addition, we have measured X-ray temperatures (TX) for 401 clusters (0.4 < TX < 14.7 keV). We highlight seven interesting subsamples of XCS-DR1 clusters: (i) 10 clusters at high redshift (z > 1.0, including a new spectroscopically confirmed cluster at z= 1.01); (ii) 66 clusters with high TX (>5 keV); (iii) 130 clusters/groups with low TX (<2 keV); (iv) 27 clusters with measured TX values in the Sloan Digital Sky Survey (SDSS) Stripe 82 co-add region; (v) 77 clusters with measured TX values in the Dark Energy Survey region; (vi) 40 clusters detected with sufficient counts to permit mass measurements (under the assumption of hydrostatic equilibrium); (vii) 104 clusters that can be used for applications such as the derivation of cosmological parameters and the measurement of cluster scaling relations. The X-ray analysis methodology used to construct and analyse the XCS-DR1 cluster sample has been presented in a companion paper, Lloyd-Davies et al.
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6.
  • Pálmadóttir, Tinna, et al. (författare)
  • Morphology-Dependent Interactions between α-Synuclein Monomers and Fibrils
  • 2023
  • Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 24:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Amyloid fibrils may adopt different morphologies depending on the solution conditions and the protein sequence. Here, we show that two chemically identical but morphologically distinct α-synuclein fibrils can form under identical conditions. This was observed by nuclear magnetic resonance (NMR), circular dichroism (CD), and fluorescence spectroscopy, as well as by cryo-transmission electron microscopy (cryo-TEM). The results show different surface properties of the two morphologies, A and B. NMR measurements show that monomers interact differently with the different fibril surfaces. Only a small part of the N-terminus of the monomer interacts with the fibril surface of morphology A, compared to a larger part of the monomer for morphology B. Differences in ThT binding seen by fluorescence titrations, and mesoscopic structures seen by cryo-TEM, support the conclusion of the two morphologies having different surface properties. Fibrils of morphology B were found to have lower solubility than A. This indicates that fibrils of morphology B are thermodynamically more stable, implying a chemical potential of fibrils of morphology B that is lower than that of morphology A. Consequently, at prolonged incubation time, fibrils of morphology B remained B, while an initially monomorphic sample of morphology A gradually transformed to B.
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7.
  • Sechopoulos, Ioannis, et al. (författare)
  • Radiation dosimetry in digital breast tomosynthesis : report of AAPM Tomosynthesis Subcommittee Task Group 223.
  • 2014
  • Ingår i: Medical physics. - : Wiley. - 2473-4209 .- 0094-2405. ; 41:9
  • Tidskriftsartikel (refereegranskat)abstract
    • The radiation dose involved in any medical imaging modality that uses ionizing radiation needs to be well understood by the medical physics and clinical community. This is especially true of screening modalities. Digital breast tomosynthesis (DBT) has recently been introduced into the clinic and is being used for screening for breast cancer in the general population. Therefore, it is important that the medical physics community have the required information to be able to understand, estimate, and communicate the radiation dose levels involved in breast tomosynthesis imaging. For this purpose, the American Association of Physicists in Medicine Task Group 223 on Dosimetry in Tomosynthesis Imaging has prepared this report that discusses dosimetry in breast imaging in general, and describes a methodology and provides the data necessary to estimate mean breast glandular dose from a tomosynthesis acquisition. In an effort to maximize familiarity with the procedures and data provided in this Report, the methodology to perform the dose estimation in DBT is based as much as possible on that used in mammography dose estimation.
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8.
  • Valleix, Sophie, et al. (författare)
  • D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Apolipoprotein C-III deficiency provides cardiovascular protection, but apolipoprotein C-III is not known to be associated with human amyloidosis. Here we report a form of amyloidosis characterized by renal insufficiency caused by a new apolipoprotein C-III variant, D25V. Despite their uremic state, the D25V-carriers exhibit low triglyceride (TG) and apolipoprotein C-III levels, and low very-low-density lipoprotein (VLDL)/high high-density lipoprotein (HDL) profile. Amyloid fibrils comprise the D25V-variant only, showing that wild-type apolipoprotein C-III does not contribute to amyloid deposition in vivo. The mutation profoundly impacts helical structure stability of D25V-variant, which is remarkably fibrillogenic under physiological conditions in vitro producing typical amyloid fibrils in its lipid-free form. D25V apolipoprotein C-III is a new human amyloidogenic protein and the first conferring cardioprotection even in the unfavourable context of renal failure, extending the evidence for an important cardiovascular protective role of apolipoprotein C-III deficiency. Thus, fibrate therapy, which reduces hepatic APOC3 transcription, may delay amyloid deposition in affected patients.
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