| 1. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 2. |
- Cormier, Marc-André, et al.
(author)
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2H-fractionations during the biosynthesis of carbohydrates and lipids imprint a metabolic signal on the δ2H values of plant organic compounds
- 2018
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In: New Phytologist. - : Wiley-Blackwell. - 0028-646X .- 1469-8137. ; 218:2, s. 479-491
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Journal article (peer-reviewed)abstract
- Hydrogen (H) isotope ratio (δ2H) analyses of plant organic compounds have been applied to assess ecohydrological processes in the environment despite a large part of the δ2H variability observed in plant compounds not being fully elucidated.We present a conceptual biochemical model based on empirical H isotope data that we generated in two complementary experiments that clarifies a large part of the unexplained variability in the δ2H values of plant organic compounds.The experiments demonstrate that information recorded in the δ2H values of plant organic compounds goes beyond hydrological signals and can also contain important information on the carbon and energy metabolism of plants. Our model explains where 2H‐fractionations occur in the biosynthesis of plant organic compounds and how these 2H‐fractionations are tightly coupled to a plant's carbon and energy metabolism. Our model also provides a mechanistic basis to introduce H isotopes in plant organic compounds as a new metabolic proxy for the carbon and energy metabolism of plants and ecosystems.Such a new metabolic proxy has the potential to be applied in a broad range of disciplines, including plant and ecosystem physiology, biogeochemistry and palaeoecology.
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| 3. |
- Herrgård, Markus J, et al.
(author)
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A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology
- 2008
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In: Nature Biotechnology. ; 26:10, s. 1155-1160
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Journal article (peer-reviewed)abstract
- Genomic data allow the large-scale manual or semi-automated assembly of metabolic network reconstructions, which provide highly curated organism-specific knowledge bases. Although several genome-scale network reconstructions describe Saccharomyces cerevisiae metabolism, they differ in scope and content, and use different terminologies to describe the same chemical entities. This make comparisons between them difficult and underscores the desirability of a consolidated metabolic network that collects and formalizes the 'community knowledge' of yeast metabolism. We describe how we have produced a consensus metabolic network reconstruction for S. cerevisiae. In drafting it, we placed special emphasis on referencing molecules to persistent databases or using database-independent forms, such as SMILES or InChl strings, as this permits their chemical structure to be represented unambiguously and in a manner that permits automated reasoning. The reconstruction is readily available via a publicly accessible database and in the Systems Biology Markup Language (http://www.comp-sys-bio.org/yeastnet). It can be maintained as a resource that serves as a common denominator for studying the systems biology of yeast. Similar strategies should benefit communities studying genome-scale metabolic networks of other organisms.
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| 4. |
- Hettmer, Simone, et al.
(author)
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Genetic testing and surveillance in infantile myofibromatosis : a report from the SIOPE Host Genome Working Group
- 2021
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In: Familial Cancer. - : Springer. - 1389-9600 .- 1573-7292. ; 20 SI:4, s. 327-336
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Journal article (peer-reviewed)abstract
- Infantile myofibromatosis (IM), which is typically diagnosed in young children, comprises a wide clinical spectrum ranging from inconspicuous solitary soft tissue nodules to multiple disseminated tumors resulting in life-threatening complications. Familial IM follows an autosomal dominant mode of inheritance and is linked toPDGFRBgermline variants. SomaticPDGFRBvariants were also detected in solitary and multifocal IM lesions.PDGFRBvariants associated with IM constitutively activate PDGFRB kinase activity in the absence of its ligand. Germline variants have lower activating capabilities than somatic variants and, thus, require a second cis-acting hit for full receptor activation. Typically, these mutant receptors remain sensitive to tyrosine kinase inhibitors such as imatinib. The SIOPE Host Genome Working Group, consisting of pediatric oncologists, clinical geneticists and scientists, met in January 2020 to discuss recommendations for genetic testing and surveillance for patients who are diagnosed with IM or have a family history of IM/PDGFRBgermline variants. This report provides a brief review of the clinical manifestations and genetics of IM and summarizes our interdisciplinary recommendations.
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| 5. |
- Kharlamova, Marianna V., et al.
(author)
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Inner tube growth properties and electronic structure of ferrocene-filled large diameter single-walled carbon nanotubes
- 2013
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In: Physica status solidi. B, Basic research. - : Wiley-VCH Verlag. - 0370-1972 .- 1521-3951. ; 250:12, s. 2575-2580
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Journal article (peer-reviewed)abstract
- We study the filling of single-walled carbon nanotubes (SW- CNTs) with ferrocene molecules. Using e-DIPS SWCNTs with a mean diameter of 1.7nm, we obtain a filling factor as high as 90%. At elevated temperatures in high vacuum the filled SWCNTs are transformed to double-walled carbon nanotubes (DWCNTs). Temperature dependence of inner tube growth is investigated by Raman spectroscopy. The electronic properties of the obtained nanostructures are studied by X-ray photoelectron spectroscopy and near edge X-ray absorption fine structure spectroscopy. It is found that the growth temperature is higher for larger diameter inner tubes. It is demonstrated that ferrocene filling leads to electron doping of SWCNTs.
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| 6. |
- McGinn, Steven, et al.
(author)
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New Technologies for DNA analysis-A review of the READNA Project.
- 2016
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In: New Biotechnology. - : Elsevier BV. - 1876-4347 .- 1871-6784.
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Research review (peer-reviewed)abstract
- The REvolutionary Approaches and Devices for Nucleic Acid analysis (READNA) project received funding from the European Commission for 4 1/2 years. The objectives of the project revolved around technological developments in nucleic acid analysis. The project partners have discovered, created and developed a huge body of insights into nucleic acid analysis, ranging from improvements and implementation of current technologies to the most promising sequencing technologies that constitute a 3(rd) and 4(th) generation of sequencing methods with nanopores and in situ sequencing, respectively.
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| 7. |
- Prát, Tomáš, et al.
(author)
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WRKY23 is a component of the transcriptional network mediating auxin feedback on PIN polarity
- 2018
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In: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 14:1
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Journal article (peer-reviewed)abstract
- Auxin is unique among plant hormones due to its directional transport that is mediated by the polarly distributed PIN auxin transporters at the plasma membrane. The canalization hypothesis proposes that the auxin feedback on its polar flow is a crucial, plant-specific mechanism mediating multiple self-organizing developmental processes. Here, we used the auxin effect on the PIN polar localization in Arabidopsis thaliana roots as a proxy for the auxin feedback on the PIN polarity during canalization. We performed microarray experiments to find regulators of this process that act downstream of auxin. We identified genes that were transcriptionally regulated by auxin in an AXR3/IAA17-and ARF7/ARF19-dependent manner. Besides the known components of the PIN polarity, such as PID and PIP5K kinases, a number of potential new regulators were detected, among which the WRKY23 transcription factor, which was characterized in more detail. Gain-and loss-of-function mutants confirmed a role for WRKY23 in mediating the auxin effect on the PIN polarity. Accordingly, processes requiring auxin-mediated PIN polarity rearrangements, such as vascular tissue development during leaf venation, showed a higher WRKY23 expression and required the WRKY23 activity. Our results provide initial insights into the auxin transcriptional network acting upstream of PIN polarization and, potentially, canalization-mediated plant development.
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| 8. |
- Sauer, Markus, et al.
(author)
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Tailoring the electronic properties of single-walled carbon nanotubes via filling with nickel acetylacetonate
- 2015
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In: Physica Status Solidi. B: Basic Research. - : Wiley. - 0370-1972. ; 252:11, s. 2546-2550
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Journal article (peer-reviewed)abstract
- Although chemical functionalization of single-walled carbon nanotubes was extensively studied, in many cases detailed information about the influence of the nanotube metallicity and diameter is missing. Here, we present an X-ray photoemission and absorption spectroscopy study of endohedrally functionalized carbon nanotubes with different diameters, where Ni(II) acetylacetonate molecules are reacted to tailor the nanotubes' electronic properties. The filling factor is found to be dependent on the SWCNT base material used. We trace the reaction process of the filling material at several annealing steps and reveal their dependence on annealing temperature, which allows doping of nanotubes to be controlled. (C) 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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| 9. |
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| 10. |
- Schubert, Jasmin S., et al.
(author)
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Elucidating the formation and active state of Cu co-catalysts for photocatalytic hydrogen evolution
- 2021
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In: Journal of Materials Chemistry A. - : Royal Society of Chemistry. - 2050-7488 .- 2050-7496. ; 9:38, s. 21958-21971
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Journal article (peer-reviewed)abstract
- The design of active and selective co-catalysts constitutes one of the major challenges in developing heterogeneous photocatalysts for energy conversion applications. This work provides a comprehensive insight into thermally induced bottom-up generation and transformation of a series of promising Cu-based co-catalysts. We demonstrate that the volcano-type HER profile as a function of calcination temperature is independent of the type of the Cu precursor but is affected by changes in oxidation state and location of the copper species. Supported by DFT modeling, our data suggest that low temperature (<200 degrees C) treatments facilitate electronic communication between the Cu species and TiO2, which allows for a more efficient charge utilization and maximum HER rates. In contrast, higher temperatures (>200 degrees C) do not affect the Cu oxidation state, but induce a gradual, temperature-dependent surface-to-bulk diffusion of Cu, which results in interstitial, tetra-coordinated Cu+ species. The disappearance of Cu from the surface and the introduction of new defect states is associated with a drop in HER performance. This work examines electronic and structural effects that are in control of the photocatalytic activity and can be transferred to other systems for further advancing photocatalysis.
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