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1.
  • Bombarda, F., et al. (author)
  • Runaway electron beam control
  • 2019
  • In: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
  • Journal article (peer-reviewed)
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2.
  • 2018
  • In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:1
  • Research review (peer-reviewed)
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3.
  • Krasilnikov, A., et al. (author)
  • Evidence of 9 Be + p nuclear reactions during 2ω CH and hydrogen minority ICRH in JET-ILW hydrogen and deuterium plasmas
  • 2018
  • In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:2
  • Journal article (peer-reviewed)abstract
    • The intensity of 9Be + p nuclear fusion reactions was experimentally studied during second harmonic (2ω CH) ion-cyclotron resonance heating (ICRH) and further analyzed during fundamental hydrogen minority ICRH of JET-ILW hydrogen and deuterium plasmas. In relatively low-density plasmas with a high ICRH power, a population of fast H+ ions was created and measured by neutral particle analyzers. Primary and secondary nuclear reaction products, due to 9Be + p interaction, were observed with fast ion loss detectors, γ-ray spectrometers and neutron flux monitors and spectrometers. The possibility of using 9Be(p, d)2α and 9Be(p, α)6Li nuclear reactions to create a population of fast alpha particles and study their behaviour in non-active stage of ITER operation is discussed in the paper.
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  • Overview of the JET results
  • 2015
  • In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 55:10
  • Journal article (peer-reviewed)
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26.
  • Romanelli, F, et al. (author)
  • Overview of the JET results
  • 2011
  • In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 51:9
  • Journal article (peer-reviewed)abstract
    • Since the last IAEA Conference JET has been in operation for one year with a programmatic focus on the qualification of ITER operating scenarios, the consolidation of ITER design choices and preparation for plasma operation with the ITER-like wall presently being installed in JET. Good progress has been achieved, including stationary ELMy H-mode operation at 4.5 MA. The high confinement hybrid scenario has been extended to high triangularity, lower ρ*and to pulse lengths comparable to the resistive time. The steady-state scenario has also been extended to lower ρ*and ν*and optimized to simultaneously achieve, under stationary conditions, ITER-like values of all other relevant normalized parameters. A dedicated helium campaign has allowed key aspects of plasma control and H-mode operation for the ITER non-activated phase to be evaluated. Effective sawtooth control by fast ions has been demonstrated with3He minority ICRH, a scenario with negligible minority current drive. Edge localized mode (ELM) control studies using external n = 1 and n = 2 perturbation fields have found a resonance effect in ELM frequency for specific q95values. Complete ELM suppression has, however, not been observed, even with an edge Chirikov parameter larger than 1. Pellet ELM pacing has been demonstrated and the minimum pellet size needed to trigger an ELM has been estimated. For both natural and mitigated ELMs a broadening of the divertor ELM-wetted area with increasing ELM size has been found. In disruption studies with massive gas injection up to 50% of the thermal energy could be radiated before, and 20% during, the thermal quench. Halo currents could be reduced by 60% and, using argon/deuterium and neon/deuterium gas mixtures, runaway electron generation could be avoided. Most objectives of the ITER-like ICRH antenna have been demonstrated; matching with closely packed straps, ELM resilience, scattering matrix arc detection and operation at high power density (6.2 MW m-2) and antenna strap voltages (42 kV). Coupling measurements are in very good agreement with TOPICA modelling. © 2011 IAEA, Vienna.
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27.
  • Abel, I, et al. (author)
  • Overview of the JET results with the ITER-like wall
  • 2013
  • In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
  • Journal article (peer-reviewed)abstract
    • Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
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28.
  • Adloff, C, et al. (author)
  • Energy flow and rapidity gaps between jets in photoproduction at HERA
  • 2002
  • In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 24:4, s. 517-527
  • Journal article (peer-reviewed)abstract
    • Dijet events in photon-proton collisions in which there is a large pseudorapidity separation, Deltaeta > 2.5 between the two highest E-T jets are studied with the H1 detector at HERA. The inclusive dijet cross sections are measured as functions of the longitudinal momentum fractions of the proton and photon which participate in the production of the jets, x(p)(jets) and x(gamma)(jets) respectively, Deltaeta, the pseudorapidity P separation between the two highest E-T jets, and E-T(gap), the total summed transverse energy between the jets. Rapidity gap events are defined as events in which E-T(gap) is less than E-T(cut), for E-T(cut) varied between jets 0.5 and 2.0 GeV. The fraction of dijet events with a rapidity gap is measured differentially in Deltaeta, x(p)(jets) and x(gamma)(jets). An excess of events with rapidity gaps at low values of E-T(cut) is observed above the expectation from standard photoproduction processes. This excess can be explained by the exchange of a strongly interacting colour singlet object between the jets.
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29.
  • Adloff, C, et al. (author)
  • Search for excited neutrinos at HERA
  • 2002
  • In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 525:1-2, s. 9-16
  • Journal article (peer-reviewed)abstract
    • We present a search for excited neutrinos using e(-) p data taken by the H1 experiment at HERA at a center-of-mass energy of 318 GeV with an integrated luminosity of 15 pb(-1). No evidence for excited neutrino production is found. Mass dependent exclusion limits are determined for the ratio of the coupling to the compositeness scale, f/Lambda, independently of the relative couplings to the SU(2) and U(1) gauge bosons. These limits extend the excluded region to higher masses than has been possible in previous searches at other colliders.
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30.
  • Adloff, C, et al. (author)
  • Measurement of D*(+/-) meson production and F-2(c) in deep-inelastic scattering at HERA
  • 2002
  • In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 528:3-4, s. 199-214
  • Journal article (peer-reviewed)abstract
    • The inclusive production of D*+/-(2010) mesons in deep-inelastic scattering is studied with the HI detector at HERA. In the kinematic region 1 < Q(2) < 100 GeV2 and 0.05 < y < 0.7 an e(+) p cross section for inclusive D*+/- meson production of 8.50 +/- 0.42(stat.)(-100)(+1.21)(syst.) nb is measured in the visible range p(tD*) > 1.5 GeV and eta(D*) < 1.5. Single and double differential inclusive D*+/- meson cross sections are compared to perturbative QCD calculations in two different evolution schemes, The charm contribution to the proton structure, F-c(2)(x, Q(2)), is determined by extrapolating the visible charm cross section to the full phase space. This contribution is found to rise from about 10% at Q(2) = 1.5 GeV2 to more than 25% at Q(2) = 60 GeV2 corresponding to x values ranging from 5 x 10(-5) to 3 x 10(-3). (C) 2002 Elsevier Science B.V. All rights reserved.
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31.
  • Adloff, C, et al. (author)
  • Measurement of dijet electroproduction at small jet separation
  • 2002
  • In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 24:1, s. 33-41
  • Journal article (peer-reviewed)abstract
    • Deep-inelastic scattering data in the range 150 < Q(2) < 35000 GeV2 are used to investigate the minimum jet separation necessary to allow accurate description of the rate of dijet production using next-to-leading order perturbative QCD calculations. The required jet separation is found to be small, allowing about 1/3 of DIS data to be classified as dijet, as opposed to approximately 1/10 with more typical jet analyses. A number of precision measurements made using this dijet sample are well described by the calculations. The data are also described by the combination of leading order matrix elements and parton showers, as implemented in the QCD based Monte Carlo model RAPGAP.
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33.
  • Strakova, A., et al. (author)
  • Recurrent horizontal transfer identifies mitochondrial positive selection in a transmissible cancer
  • 2020
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
  • Journal article (peer-reviewed)abstract
    • Autonomous replication and segregation of mitochondrial DNA (mtDNA) creates the potential for evolutionary conflict driven by emergence of haplotypes under positive selection for 'selfish' traits, such as replicative advantage. However, few cases of this phenomenon arising within natural populations have been described. Here, we survey the frequency of mtDNA horizontal transfer within the canine transmissible venereal tumour (CTVT), a contagious cancer clone that occasionally acquires mtDNA from its hosts. Remarkably, one canine mtDNA haplotype, A1d1a, has repeatedly and recently colonised CTVT cells, recurrently replacing incumbent CTVT haplotypes. An A1d1a control region polymorphism predicted to influence transcription is fixed in the products of an A1d1a recombination event and occurs somatically on other CTVT mtDNA backgrounds. We present a model whereby 'selfish' positive selection acting on a regulatory variant drives repeated fixation of A1d1a within CTVT cells.
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35.
  • Agirre, Jon, et al. (author)
  • The CCP4 suite: integrative software for macromolecular crystallography
  • 2023
  • In: Acta Crystallographica Section D. - : INT UNION CRYSTALLOGRAPHY. - 2059-7983. ; 79, s. 449-461
  • Journal article (peer-reviewed)abstract
    • The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces. The CCP4 suite has experienced several considerable changes since its last reference article, involving new infrastructure, original programs and graphical interfaces. This article, which is intended as a general literature citation for the use of the CCP4 software suite in structure determination, will guide the reader through such transformations, offering a general overview of the new features and outlining future developments. As such, it aims to highlight the individual programs that comprise the suite and to provide the latest references to them for perusal by crystallographers around the world.
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37.
  • Hall, C. Michael, et al. (author)
  • Denying bogus skepticism in climate change and tourism research.
  • 2015
  • In: Tourism Management. - : Elsevier BV. - 0261-5177 .- 1879-3193. ; 47, s. 352-356
  • Journal article (peer-reviewed)abstract
    • This final response to the two climate change denial papers by Shani and Arad further highlights the inaccuracies, misinformation and errors in their commentaries. The obfuscation of scientific research and the consensus on anthropogenic climate change may have significant long-term negative consequences for better understanding the implications of climate change and climate policy for tourism and create confusion and delay in developing and implementing tourism sector responses.
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38.
  • Hall, C. Michael, et al. (author)
  • No time for smokescreen skepticism : A rejoinder to Shani and Arad
  • 2015
  • In: Tourism Management. - : Elsevier BV. - 0261-5177 .- 1879-3193. ; 47, s. 341-347
  • Journal article (peer-reviewed)abstract
    • Shani and Arad (2014) claimed that tourism scholars tend to endorse the most pessimistic assessments regarding climate change, and that anthropogenic climate change was a "fashionable" and "highly controversial scientific topic". This brief rejoinder provides the balance that is missing from such climate change denial and skepticism studies on climate change and tourism. Recent research provides substantial evidence that reports on anthropogenic climate change are accurate, and that human-induced greenhouse gas emissions, including from the tourism industry, play a significant role in climate change. Some positive net effects may be experienced by some destinations in the short-term, but in the long-term all elements of the tourism system will be impacted. The expansion of tourism emissions at a rate greater than efficiency gains means that it is increasingly urgent that the tourism sector acknowledge, accept and respond to climate change. Debate on tourism-related adaptation and mitigation measures is to be encouraged and welcomed. Climate change denial is not.
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39.
  • Correa, J., et al. (author)
  • On the Charge Collection Efficiency of the PERCIVAL Detector
  • 2016
  • In: Journal of Instrumentation. - : IOP. - 1748-0221. ; 11:12
  • Journal article (peer-reviewed)abstract
    • The PERCIVAL soft X-ray imager is being developed by DESY, RAL, Elettra, DLS, and PAL to address the challenges at high brilliance Light Sources such as new-generation Synchrotrons and Free Electron Lasers. Typical requirements for detector systems at these sources are high frame rates, large dynamic range, single-photon counting capability with low probability of false positives, high quantum efficiency, and (multi)-mega-pixel arrangements. PERCIVAL is a monolithic active pixel sensor, based on CMOS technology. It is designed for the soft X-ray regime and, therefore, it is post-processed in order to achieve high quantum efficiency in its primary energy range (250 eV to 1 keV) . This work will report on the latest experimental results on charge collection efficiency obtained for multiple back-side-illuminated test sensors during two campaigns, at the P04 beam-line at PETRA III, and the CiPo beam-line at Elettra, spanning most of the primary energy range as well as testing the performance for photon-energies below 250 eV . In addition, XPS surface analysis was used to cross-check the obtained results.
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40.
  • Figtree, Gemma A., et al. (author)
  • Clinical Pathway for Coronary Atherosclerosis in Patients Without Conventional Modifiable Risk Factors JACC State-of-the-Art Review
  • 2023
  • In: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 82:13, s. 1343-1359
  • Research review (peer-reviewed)abstract
    • Reducing the incidence and prevalence of standard modifiable cardiovascular risk factors (SMuRFs) is critical to tackling the global burden of coronary artery disease (CAD). However, a substantial number of individuals develop coronary atherosclerosis despite no SMuRFs. SMuRFless patients presenting with myocardial infarction have been observed to have an unexpected higher early mortality compared to their counterparts with at least 1 SMuRF. Evidence for optimal management of these patients is lacking. We assembled an international, multidisciplinary team to develop an evidence-based clinical pathway for SMuRFless CAD patients. A modified Delphi method was applied. The resulting pathway confirms underlying atherosclerosis and true SMuRFless status, ensures evidence-based secondary prevention, and considers additional tests and interventions for less typical contributors. This dedicated pathway for a previously overlooked CAD population, with an accompanying registry, aims to improve outcomes through enhanced adherence to evidence-based secondary prevention and additional diagnosis of modifiable risk factors observed. (c) 2023 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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41.
  • Mikkelsen, Tarjei S, et al. (author)
  • Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences
  • 2007
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7141, s. 167-177
  • Journal article (peer-reviewed)abstract
    • We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As the first metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation.
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43.
  • Khromova, A., et al. (author)
  • Report on recent results of the PERCIVAL soft X-ray imager
  • 2016
  • In: Journal of Instrumentation. - : IOP. - 1748-0221. ; 11:November
  • Journal article (peer-reviewed)abstract
    • The PERCIVAL (Pixelated Energy Resolving CMOS Imager, Versatile And Large) soft X-ray 2D imaging detector is based on stitched, wafer-scale sensors possessing a thick epi-layer, which together with back-thinning and back-side illumination yields elevated quantum efficiency in the photon energy range of 125–1000 eV. Main application fields of PERCIVAL are foreseen in photon science with FELs and synchrotron radiation. This requires high dynamic range up to 105 ph @ 250 eV paired with single photon sensitivity with high confidence at moderate frame rates in the range of 10–120 Hz. These figures imply the availability of dynamic gain switching on a pixel-by-pixel basis and a highly parallel, low noise analog and digital readout, which has been realized in the PERCIVAL sensor layout. Different aspects of the detector performance have been assessed using prototype sensors with different pixel and ADC types. This work will report on the recent test results performed on the newest chip prototypes with the improved pixel and ADC architecture. For the target frame rates in the 10–120 Hz range an average noise floor of 14e− has been determined, indicating the ability of detecting single photons with energies above 250 eV. Owing to the successfully implemented adaptive 3-stage multiple-gain switching, the integrated charge level exceeds 4 centerdot 106 e− or 57000 X-ray photons at 250 eV per frame at 120 Hz. For all gains the noise level remains below the Poisson limit also in high-flux conditions. Additionally, a short overview over the updates on an oncoming 2 Mpixel (P2M) detector system (expected at the end of 2016) will be reported.
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44.
  • Correa, J., et al. (author)
  • The PERCIVAL detector : first user experiments
  • 2023
  • In: Journal of Synchrotron Radiation. - 0909-0495 .- 1600-5775. ; 30, s. 242-250
  • Journal article (peer-reviewed)abstract
    • The PERCIVAL detector is a CMOS imager designed for the soft X-ray regime at photon sources. Although still in its final development phase, it has recently seen its first user experiments: ptychography at a free-electron laser, holographic imaging at a storage ring and preliminary tests on X-ray photon correlation spectroscopy. The detector performed remarkably well in terms of spatial resolution achievable in the sample plane, owing to its small pixel size, large active area and very large dynamic range; but also in terms of its frame rate, which is significantly faster than traditional CCDs. In particular, it is the combination of these features which makes PERCIVAL an attractive option for soft X-ray science.
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45.
  • Erdinc, Direnis, et al. (author)
  • Pathological variants in TOP3A cause distinct disorders of mitochondrial and nuclear genome stability
  • 2023
  • In: Embo Molecular Medicine. - 1757-4676. ; 15:5
  • Journal article (peer-reviewed)abstract
    • Topoisomerase 3 alpha (TOP3A) is an enzyme that removes torsional strain and interlinks between DNA molecules. TOP3A localises to both the nucleus and mitochondria, with the two isoforms playing specialised roles in DNA recombination and replication respectively. Pathogenic variants in TOP3A can cause a disorder similar to Bloom syndrome, which results from bi-allelic pathogenic variants in BLM, encoding a nuclear-binding partner of TOP3A. In this work, we describe 11 individuals from 9 families with an adult-onset mitochondrial disease resulting from bi-allelic TOP3A gene variants. The majority of patients have a consistent clinical phenotype characterised by bilateral ptosis, ophthalmoplegia, myopathy and axonal sensory-motor neuropathy. We present a comprehensive characterisation of the effect of TOP3A variants, from individuals with mitochondrial disease and Bloom-like syndrome, upon mtDNA maintenance and different aspects of enzyme function. Based on these results, we suggest a model whereby the overall severity of the TOP3A catalytic defect determines the clinical outcome, with milder variants causing adult-onset mitochondrial disease and more severe variants causing a Bloom-like syndrome with mitochondrial dysfunction in childhood.
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46.
  • Imai, Y., et al. (author)
  • Identification of oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury
  • 2008
  • In: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 133:2, s. 235-249
  • Journal article (peer-reviewed)abstract
    • Multiple lung pathogens such as chemical agents, H5N1 avian flu, or SARS cause high lethality due to acute respiratory distress syndrome. Here we report that Toll-like receptor 4 (TLR4) mutant mice display natural resistance to acid-induced acute lung injury (ALI). We show that TLR4-TRIF-TRAF6 signaling is a key disease pathway that controls the severity of ALI. The oxidized phospholipid (OxPL) OxPAPC was identified to induce lung injury and cytokine production by lung macrophages via TLR4-TRIF. We observed OxPL production in the lungs of humans and animals infected with SARS, Anthrax, or H5N1. Pulmonary challenge with an inactivated H5N1 avian influenza virus rapidly induces ALI and OxPL formation in mice. Loss of TLR4 or TRIF expression protects mice from H5N1-induced ALI. Moreover, deletion of ncf1, which controls ROS production, improves the severity of H5N1-mediated ALI. Our data identify oxidative stress and innate immunity as key lung injury pathways that control the severity of ALI.
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47.
  • Jiang, M., et al. (author)
  • The mitochondrial single-stranded DNA binding protein is essential for initiation of mtDNA replication
  • 2021
  • In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:27
  • Journal article (peer-reviewed)abstract
    • We report a role for the mitochondrial single-stranded DNA binding protein (mtSSB) in regulating mitochondrial DNA (mtDNA) replication initiation in mammalian mitochondria. Transcription from the light-strand promoter (LSP) is required both for gene expression and for generating the RNA primers needed for initiation of mtDNA synthesis. In the absence of mtSSB, transcription from LSP is strongly up-regulated, but no replication primers are formed. Using deep sequencing in a mouse knockout model and biochemical reconstitution experiments with pure proteins, we find that mtSSB is necessary to restrict transcription initiation to optimize RNA primer formation at both origins of mtDNA replication. Last, we show that human pathological versions of mtSSB causing severe mitochondrial disease cannot efficiently support primer formation and initiation of mtDNA replication. © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.
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48.
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49.
  • Patterson, Nick, et al. (author)
  • Large-scale migration into Britain during the Middle to Late Bronze Age
  • 2022
  • In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
  • Journal article (peer-reviewed)abstract
    • Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
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50.
  • Menger, K. E., et al. (author)
  • Two type I topoisomerases maintain DNA topology in human mitochondria
  • 2022
  • In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 50:19, s. 11154-11174
  • Journal article (peer-reviewed)abstract
    • Genetic processes require the activity of multiple topoisomerases, essential enzymes that remove topological tension and intermolecular linkages in DNA. We have investigated the subcellular localisation and activity of the six human topoisomerases with a view to understanding the topological maintenance of human mitochondrial DNA. Our results indicate that mitochondria contain two topoisomerases, TOP1MT and TOP3A. Using molecular, genomic and biochemical methods we find that both proteins contribute to mtDNA replication, in addition to the decatenation role of TOP3A, and that TOP1MT is stimulated by mtSSB. Loss of TOP3A or TOP1MT also dysregulates mitochondrial gene expression, and both proteins promote transcription elongation in vitro. We find no evidence for TOP2 localisation to mitochondria, and TOP2B knockout does not affect mtDNA maintenance or expression. Our results suggest a division of labour between TOP3A and TOP1MT in mtDNA topology control that is required for the proper maintenance and expression of human mtDNA.
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