| 1. |
- Fresard, Laure, et al.
(author)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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In: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Journal article (peer-reviewed)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 2. |
- Paschke, K. D., et al.
(author)
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Experimental determination of the complete spin structure for (p)over-barp ->(Lambda)over-bar Lambda at p((p)over-bar)=1.637 GeV/c
- 2006
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In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 74:1, s. 015206-
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Journal article (peer-reviewed)abstract
- The reaction (p) over barp -> (Lambda) over bar Lambda -> (p) over bar pi(+)p pi(-) has been measured with high statistics at a beam momentum of p((p) over bar)=1.637GeV/c. The use of a transversely polarized frozen-spin target combined with the self-analyzing property of Lambda/(Lambda) over bar decay allows access to unprecedented information on the spin structure of the interaction. The most general spin-scattering matrix can be written in terms of 11 real parameters for each bin of scattering angle; each of these parameters is determined with reasonable precision. From these results, all conceivable spin correlations are determined with inherent self-consistency. Good agreement is found with the few previously existing measurements of spin observables in (p) over barp ->(Lambda) over bar Lambda near this energy. Existing theoretical models do not give good predictions for those spin observables that had not been previously measured.
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| 3. |
- Schoch, C. L., et al.
(author)
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A class-wide phylogenetic assessment of Dothideomycetes
- 2009
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In: Studies in mycology. - : Westerdijk Fungal Biodiversity Institute. - 0166-0616 .- 1872-9797. ; 64, s. 1-15
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Research review (peer-reviewed)abstract
- We present a comprehensive phylogeny derived from 5 genes, nucSSU, nucLSU rDNA, TEF1, RPB1 and RPB2, for 356 isolates and 41 families (six newly described in this volume) in Dothideomycetes. All currently accepted orders in the class are represented for the first time in addition to numerous previously unplaced lineages. Subclass Pleosporomycetidae is expanded to include the aquatic order Jahnulales. An ancestral reconstruction of basic nutritional modes supports numerous transitions from saprobic life histories to plant associated and lichenised modes and a transition from terrestrial to aquatic habitats are confirmed. Finally, a genomic comparison of 6 dothideomycete genomes with other fungi finds a high level of unique protein associated with the class, supporting its delineation as a separate taxon.
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| 4. |
- Ahrens, J, et al.
(author)
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First measurement of the helicity-dependent (gamma)over-right-arrow(p)over-right-arrow -> p eta differential cross-section
- 2003
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In: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001. ; 17:2, s. 241-244
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Journal article (peer-reviewed)abstract
- The helicity dependence of the (γ) over right arrow(p) over right arrow -+ peta reaction has been measured for the first time at a center-of-mass angle theta(eta)*= 70degrees in the photon energy range from 780 MeV to 790 MeV. The experiment, performed at the Mainz microtron MAMI, used a 4pi-detector system, a circularly polarized, tagged photon beam. and a longitudinally polarized frozen-spin target. The helicity 3/2 cross-section is found to be small and the results for helicity 1/2 agree with predictions from the MAID analysis.
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| 5. |
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| 6. |
- Ahrens, J, et al.
(author)
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Helicity dependence of the (gamma)over-right-arrow (p)over-right-arrow -> n pi(+) pi(0) reaction in the second resonance region
- 2003
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In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 551:1-2, s. 49-55
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Journal article (peer-reviewed)abstract
- The helicity dependence of the total cross section for the (γ) over right arrow(p) over right arrownpi(+) pi(0) reaction has been measured for the first time at incident photon energies from 400 to 800 MeV The measurement was performed with the large acceptance detector DAPHNE at the tagged photon beam facility of the MAMI accelerator in Mainz. This channel is found to be excited predominantly when the photon and proton have a parallel spin orientation, due to the intermediate production of the D-13 resonance. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 7. |
- Ahrens, J, et al.
(author)
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Helicity dependence of the gamma p -> N pi channels and multipole analysis in the Delta region
- 2004
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In: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001. ; 21:2, s. 323-333
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Journal article (peer-reviewed)abstract
- A high-quality double-polarization data set for the helicity dependence of the total and differential cross-sections for both gammap --> Npi channels in the Delta region has been obtained in the framework of the GDH experiment. The experiment, performed at the Mainz microtron MAMI, used a 4pi detection system, a circularly polarized photon beam, and a longitudinally polarized frozen-spin target. These data are included in the database to perform a multipole analysis to determine the properties of the Delta(1232)-resonance. For the resonant Delta(1232) multipoles we find a very good agreement with previous analyses, while the nonresonant ones show significant deviations.
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| 8. |
- Ahrens, J, et al.
(author)
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Intermediate resonance excitation in the gamma p -> p pi(0)pi(0) reaction
- 2005
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In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 624:3-4, s. 173-180
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Journal article (peer-reviewed)abstract
- The helicity dependence of the total cross section for the (gamma) over right arrow(p) over right arrow -> p pi(0)pi(0) reaction has been measured for the first time at incident photon energies from 400 to 800 MeV. The measurement, performed at the tagged photon beam facility of the MAMI accelerator in Mainz, used the large acceptance detector DAPHNE and a longitudinally polarized frozen-spin target. This channel is found to be excited predominantly when the photon and proton have a parallel spin orientation, most likely due to the intermediate production of the D-13(1520) resonance. However, the contribution of the antiparallel spin configuration, arising from other reaction mechanisms, is also not negligible. This result gives important new information to resolve the existing model discrepancies in the identification of the nucleon resonances contributing to this channel.
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| 9. |
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| 10. |
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| 11. |
- Schoch, CL, et al.
(author)
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Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi
- 2012
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 109:16, s. 6241-6246
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Journal article (peer-reviewed)abstract
- Six DNA regions were evaluated as potential DNA barcodes for Fungi, the second largest kingdom of eukaryotic life, by a multinational, multilaboratory consortium. The region of the mitochondrial cytochrome c oxidase subunit 1 used as the animal barcode was excluded as a potential marker, because it is difficult to amplify in fungi, often includes large introns, and can be insufficiently variable. Three subunits from the nuclear ribosomal RNA cistron were compared together with regions of three representative protein-coding genes (largest subunit of RNA polymerase II, second largest subunit of RNA polymerase II, and minichromosome maintenance protein). Although the protein-coding gene regions often had a higher percent of correct identification compared with ribosomal markers, low PCR amplification and sequencing success eliminated them as candidates for a universal fungal barcode. Among the regions of the ribosomal cistron, the internal transcribed spacer (ITS) region has the highest probability of successful identification for the broadest range of fungi, with the most clearly defined barcode gap between inter- and intraspecific variation. The nuclear ribosomal large subunit, a popular phylogenetic marker in certain groups, had superior species resolution in some taxonomic groups, such as the early diverging lineages and the ascomycete yeasts, but was otherwise slightly inferior to the ITS. The nuclear ribosomal small subunit has poor species-level resolution in fungi. ITS will be formally proposed for adoption as the primary fungal barcode marker to the Consortium for the Barcode of Life, with the possibility that supplementary barcodes may be developed for particular narrowly circumscribed taxonomic groups.
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| 12. |
- Dutz, H, et al.
(author)
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Experimental check of the Gerasimov-Drell-Hearn sum rule for H-1
- 2004
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In: Physical Review Letters. - 1079-7114. ; 93:3
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Journal article (peer-reviewed)abstract
- For the first time we checked the fundamental Gerasimov-Drell-Hearn (GDH) sum rule for the proton experimentally in the photon energy range from 0.2-2.9 GeV with the tagged photon facilities at MAMI (Mainz) and ELSA (Bonn). New data of the doubly polarized total cross section difference are presented in the energy range from 1.6 to 2.9 GeV. The contribution to the GDH integral from 0.2-2.9 GeV yields [254+/-5(stat)+/-12(syst)] mub with negative contributions in the Regge regime at photon energies above 2.1 GeV. This trend supports the validity of the GDH sum rule.
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| 13. |
- Dutz, H, et al.
(author)
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First measurement of the Gerasimov-Drell-Hearn sum rule for H-1 from 0.7 to 1.8 GeV at ELSA
- 2003
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In: Physical Review Letters. - 1079-7114. ; 91:19: 192001
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Journal article (peer-reviewed)abstract
- To verify the fundamental Gerasimov-Drell-Hearn (GDH) sum rule for the first time experimentally, we measured the helicity dependent total photoabsorption cross section with circularly polarized real photons and longitudinally polarized nucleons in the photon energy range 0.68-1.82 GeV with the tagged photon facility at ELSA. The experiment was carried out with a 4pi detection system, a circularly polarized tagged photon beam, and a frozen spin polarized proton target. The contribution to the GDH sum rule in this photon energy range is [49.9+/-2.4(stat)+/-2.2(syst)] mub.
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| 14. |
- Dutz, H, et al.
(author)
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Measurement of helicity-dependent photoabsorption cross sections on the neutron from 815 to 1825 MeV
- 2005
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In: Physical Review Letters. - 1079-7114. ; 94
-
Journal article (peer-reviewed)abstract
- Helicity-dependent total photoabsorption cross sections on the deuteron have been measured for the first time at ELSA (Bonn) in the photon energy range from 815 to 1825 MeV. Circularly polarized tagged photons impinging on a longitudinally polarized LiD target have been used together with a highly efficient 4 pi detector system. The data around 1 GeV are not compatible with predictions from existing multipole analyses. From the measured energy range an experimental contribution to the GDH integral on the neutron of [33.9 +/- 5.5(stat)+/- 4.5(syst)] mu b is extracted.
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| 15. |
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| 16. |
- Naumova, M., et al.
(author)
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Structural dynamics upon photoexcitation-induced charge transfer in a dicopper(i)-disulfide complex
- 2018
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In: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9084 .- 1463-9076. ; 20:9, s. 6274-6286
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Journal article (peer-reviewed)abstract
- The structural dynamics of charge-transfer states of nitrogen-ligated copper complexes has been extensively investigated in recent years following the development of pump-probe X-ray techniques. In this study we extend this approach towards copper complexes with sulfur coordination and investigate the influence of charge transfer states on the structure of a dicopper(i) complex with coordination by bridging disulfide ligands and additionally tetramethylguanidine units [Cu I 2 (NSSN) 2 ] 2+ . In order to directly observe and refine the photoinduced structural changes in the solvated complex we applied picosecond pump-probe X-ray absorption spectroscopy (XAS) and wide-angle X-ray scattering (WAXS). Additionally, the ultrafast evolution of the electronic excited states was monitored by femtosecond transient absorption spectroscopy in the UV-Vis probe range. DFT calculations were used to predict molecular geometries and electronic structures of the ground and metal-to-ligand charge transfer states with singlet and triplet spin multiplicities, i.e. S 0 , 1 MLCT and 3 MLCT, respectively. Combining these techniques we elucidate the electronic and structural dynamics of the solvated complex upon photoexcitation to the MLCT states. In particular, femtosecond optical transient spectroscopy reveals three distinct timescales of 650 fs, 10 ps and > 100 ps, which were assigned as internal conversion to the ground state (S n → S 0 ), intersystem crossing 1 MLCT → 3 MLCT, and subsequent relaxation of the triplet to the ground state, respectively. Experimental data collected using both X-ray techniques are in agreement with the DFT-predicted structure for the triplet state, where coordination bond lengths change and one of the S-S bridges is cleaved, causing the movement of two halves of the molecule relative to each other. Extended X-ray absorption fine structure spectroscopy resolves changes in Cu-ligand bond lengths with precision on the order of 0.01 Å, whereas WAXS is sensitive to changes in the global shape related to relative movement of parts of the molecule. The results presented herein widen the knowledge on the electronic and structural dynamics of photoexcited copper-sulfur complexes and demonstrate the potential of combining the pump-probe X-ray absorption and scattering for studies on photoinduced structural dynamics in copper-based coordination complexes.
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| 17. |
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| 18. |
- Hibbett, D. S., et al.
(author)
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A higher-level phylogenetic classification of the Fungi
- 2007
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In: Mycological Research. - : Elsevier BV. - 0953-7562 .- 1469-8102. ; 111, s. 509-547
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Journal article (peer-reviewed)abstract
- A comprehensive phylogenetic classification of the kingdom Fungi is proposed, with reference to recent molecular phylogenetic analyses, and with input from diverse members of the fungal taxonomic community. The classification includes 195 taxa, down to the level of order, of which 16 are described or validated here: Dikarya subkingdom nov.; Chytridiomycota, Neocallimastigomycota phyla nov.; Monoblepharidomycetes, Neocallimastigomycetes class. nov.; Eurotiomycetidae, Lecarioromycetidae, Mycocaliciomycetidae subclass. nov.; Acarosporales, Corticiales, Baeomycetales, Candelariales, Gloeophyllales, Melanosporales, Trechisporales, Umbilicariales ords. nov. The clade containing Ascomycota and Basidiomycota is classified as subkingdom Dikarya, reflecting the putative synapomorphy of dikaryotic hyphae. The most dramatic shifts in the classification relative to previous works concern the groups that have traditionally been included in the Chytridiomycota and Zygomycota. The Chytridiomycota is retained in a restricted sense, with Blastocladiomycota and Neocallimastigomycota representing segregate phyla of flagellated Fungi. Taxa traditionally placed in Zygomycota are distributed among Glomeromycota and several subphyla incertae sedis, including Mucoromycotina, Entomophthoromycotina, Kickxellomycotina, and Zoopagomycotiria. Microsporidia are included in the Fungi, but no further subdivision of the group is proposed. Several genera of 'basal' Fungi of uncertain position are not placed in any higher taxa, including Basidiobolus, Caulochytrium, Olpidium, and Rozella. (c) 2007 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.
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| 19. |
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| 20. |
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| 21. |
- Lucking, R., et al.
(author)
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Fungal taxonomy and sequence-based nomenclature
- 2021
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In: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 6:5, s. 540-548
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Journal article (peer-reviewed)abstract
- The identification and proper naming of microfungi, in particular plant, animal and human pathogens, remains challenging. Molecular identification is becoming the default approach for many fungal groups, and environmental metabarcoding is contributing an increasing amount of sequence data documenting fungal diversity on a global scale. This includes lineages represented only by sequence data. At present, these taxa cannot be formally described under the current nomenclature rules. By considering approaches used in bacterial taxonomy, we propose solutions for the nomenclature of taxa known only from sequences to facilitate consistent reporting and communication in the literature and public sequence repositories. This Perspective discusses fungal taxonomy and provides guidance for the naming of fungal taxa known only from sequences.
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| 22. |
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| 23. |
- Schaberg, T, et al.
(author)
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[Tuberculosis Guideline for Adults - Guideline for Diagnosis and Treatment of Tuberculosis including LTBI Testing and Treatment of the German Central Committee (DZK) and the German Respiratory Society (DGP)]
- 2017
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In: Pneumologie (Stuttgart, Germany). - : Georg Thieme Verlag KG. - 1438-8790 .- 0934-8387. ; 71:6, s. 325-397
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Journal article (peer-reviewed)abstract
- In Deutschland ist seit 2015 ein deutlicher Anstieg der gemeldeten Tuberkulosefälle zu verzeichnen. Zurückzuführen ist dieser vor allem auf die aktuell vermehrte Migration. Durch die niedrige Inzidenz in den vorhergehenden Jahren konzentriert sich die Erfahrung im Umgang mit Tuberkulose immer mehr auf spezialisierte Zentren. Pneumologen wie auch andere Fachbereiche sind nun aber wieder häufiger an der Behandlung einer Tuberkulose beteiligt, sodass Fachwissen zur Standardtherapie wie auch zu selteneren Therapiesituationen benötigt wird. Die aktuelle Leitlinie zur Diagnostik und Therapie, einschließlich Chemoprävention und -prophylaxe im Erwachsenenalter fasst den derzeitigen Wissensstand zusammen und passt die Empfehlungen an die Situation in Deutschland an. Realisiert wurde die AWMF S2k-Leitlinie durch das Deutsche Zentralkomitee zur Bekämpfung der Tuberkulose e. V. (DZK) im Auftrag der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e. V. (DGP). Zur Behandlung der Tuberkulose im pädiatrischen Bereich wird in Kürze eine eigenständige Leitlinie der entsprechenden Fachgesellschaften veröffentlicht. Im Vergleich zu den Empfehlungen von 2012 sind eigenständige Kapitel zur Labordiagnostik und zum therapeutischen Medikamentenmanagement entstanden. Die Kapitel Mehrfachresistenzen gegen Medikamente der Standardtherapie, HIV-Koinfektion und die Übersicht der Arzneimittel wurden erweitert. Die umfangreiche Überarbeitung der Empfehlungen soll Ärzten und auch anderen Beschäftigten im Gesundheitswesen helfen, den aktuellen Herausforderungen im Umgang mit dem selten gewordenen Tuberkuloseerreger zu begegnen.
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