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  • 201. Zaghlool, Ammar
    et al.
    Ameur, Adam
    Wu, Chenglin
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Orzechowski Westholm, Jakub
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Niazi, Adnan
    Manivannan, Manimozhi
    Bramlett, Kelli
    Nilsson, Mats
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab). Uppsala University, Sweden.
    Feuk, Lars
    Expression profiling and in situ screening of circular RNAs in human tissues2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 16953Article in journal (Refereed)
    Abstract [en]

    Circular RNAs (circRNAs) were recently discovered as a class of widely expressed noncoding RNA and have been implicated in regulation of gene expression. However, the function of the majority of circRNAs remains unknown. Studies of circRNAs have been hampered by a lack of essential approaches for detection, quantification and visualization. We therefore developed a target-enrichment sequencing method suitable for screening of circRNAs and their linear counterparts in large number of samples. We also applied padlock probes and in situ sequencing to visualize and determine circRNA localization in human brain tissue at subcellular levels. We measured circRNA abundance across different human samples and tissues. Our results highlight the potential of this RNA class to act as a specific diagnostic marker in blood and serum, by detection of circRNAs from genes exclusively expressed in the brain. The powerful and scalable tools we present will enable studies of circRNA function and facilitate screening of circRNA as diagnostic biomarkers.

  • 202. Zapata, Luis
    et al.
    Susak, Hana
    Drechsel, Oliver
    Friedländer, Marc R.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Stockholm University, Science for Life Laboratory (SciLifeLab). The Barcelona Institute of Science and Technology, Spain; Universitat Pompeu Fabra (UPF), Spain.
    Estivill, Xavier
    Ossowski, Stephan
    Signatures of positive selection reveal a universal role of chromatin modifiers as cancer driver genes2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 13124Article in journal (Refereed)
    Abstract [en]

    Tumors are composed of an evolving population of cells subjected to tissue-specific selection, which fuels tumor heterogeneity and ultimately complicates cancer driver gene identification. Here, we integrate cancer cell fraction, population recurrence, and functional impact of somatic mutations as signatures of selection into a Bayesian model for driver prediction. We demonstrate that our model, cDriver, outperforms competing methods when analyzing solid tumors, hematological malignancies, and pan-cancer datasets. Applying cDriver to exome sequencing data of 21 cancer types from 6,870 individuals revealed 98 unreported tumor type-driver gene connections. These novel connections are highly enriched for chromatin-modifying proteins, hinting at a universal role of chromatin regulation in cancer etiology. Although infrequently mutated as single genes, we show that chromatin modifiers are altered in a large fraction of cancer patients. In summary, we demonstrate that integration of evolutionary signatures is key for identifying mutational driver genes, thereby facilitating the discovery of novel therapeutic targets for cancer treatment.

  • 203. Zeng, Lunjie
    et al.
    Tran, Dung Trung
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Tai, Cheuk-Wai
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Svensson, Gunnar
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Olsson, Eva
    Atomic structure and oxygen deficiency of the ultrathin aluminium oxide barrier in Al/AlOx/Al Josephson junctions2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 29679Article in journal (Refereed)
    Abstract [en]

    Al/AlOx/Al Josephson junctions are the building blocks of a wide range of superconducting quantum devices that are key elements for quantum computers, extremely sensitive magnetometers and radiation detectors. The properties of the junctions and the superconducting quantum devices are determined by the atomic structure of the tunnel barrier. The nanoscale dimension and disordered nature of the barrier oxide have been challenges for the direct experimental investigation of the atomic structure of the tunnel barrier. Here we show that the miniaturized dimension of the barrier and the interfacial interaction between crystalline Al and amorphous AlOx give rise to oxygen deficiency at the metal/oxide interfaces. In the interior of the barrier, the oxide resembles the atomic structure of bulk aluminium oxide. Atomic defects such as oxygen vacancies at the interfaces can be the origin of the two-level systems and contribute to decoherence and noise in superconducting quantum circuits.

  • 204.
    Zguna, Nadezda
    et al.
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Karlson, Agnes M. L.
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry. Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Ilag, Leopold L.
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Garbaras, Andrius
    Gorokhova, Elena
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Insufficient evidence for BMAA transfer in the pelagic and benthic food webs in the Baltic Sea2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 10406Article in journal (Refereed)
    Abstract [en]

    The evidence regarding BMAA occurrence in the Baltic Sea is contradictory, with benthic sources appearing to be more important than pelagic ones. The latter is counterintuitive considering that the identified sources of this compound in the food webs are pelagic primary producers, such as diatoms, dinoflagellates, and cyanobacteria. To elucidate BMAA distribution, we analyzed BMAA in the pelagic and benthic food webs in the Northern Baltic Proper. As potential sources, phytoplankton communities were used. Pelagic food chain was represented by zooplankton, mysids and zooplanktivorous fish, whereas benthic invertebrates and benthivorous fish comprised the benthic chain. The trophic structure of the system was confirmed by stable isotope analysis. Contrary to the reported ubiquitous occurrence of BMAA in the Baltic food webs, only phytoplankton, zooplankton and mysids tested positive, whereas no measurable levels of this compound occurred in the benthic invertebrates and any of the tested fish species. These findings do not support the widely assumed occurrence and transfer of BMAA to the top consumers in the Baltic food webs. More controlled experiments and field observations are needed to understand the transfer and possible transformation of BMAA in the food web under various environmental settings.

  • 205. Zhang, Huan
    et al.
    Werner, Johannes P.
    García-Bustamante, Elena
    González-Rouco, Fidel
    Wagner, Sebastian
    Zorita, Eduardo
    Fraedrich, Klaus
    Jungclaus, Johann H.
    Charpentier Ljungqvist, Fredrik
    Stockholm University, Faculty of Humanities, Department of History.
    Zhu, Xiuhua
    Xoplaki, Elena
    Chen, Fahu
    Duan, Jianping
    Ge, Quansheng
    Hao, Zhixin
    Ivanov, Martin
    Schneider, Lea
    Talento, Stefanie
    Wang, Jianglin
    Yang, Bao
    Luterbacher, Jürg
    East Asian warm season temperature variations over the past two millennia2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 7702Article in journal (Refereed)
    Abstract [en]

    East Asia has experienced strong warming since the 1960s accompanied by an increased frequency of heat waves and shrinking glaciers over the Tibetan Plateau and the Tien Shan. Here, we place the recent warmth in a long-term perspective by presenting a new spatially resolved warm-season (May-September) temperature reconstruction for the period 1-2000 CE using 59 multiproxy records from a wide range of East Asian regions. Our Bayesian Hierarchical Model (BHM) based reconstructions generally agree with earlier shorter regional temperature reconstructions but are more stable due to additional temperature sensitive proxies. We find a rather warm period during the first two centuries CE, followed by a multi-century long cooling period and again a warm interval covering the 900-1200 CE period (Medieval Climate Anomaly, MCA). The interval from 1450 to 1850 CE (Little Ice Age, LIA) was characterized by cooler conditions and the last 150 years are characterized by a continuous warming until recent times. Our results also suggest that the 1990s were likely the warmest decade in at least 1200 years. The comparison between an ensemble of climate model simulations and our summer reconstructions since 850 CE shows good agreement and an important role of internal variability and external forcing on multi-decadal time-scales.

  • 206. Zhang, Zhaohui
    et al.
    Smittenberg, Rienk H.
    Stockholm University, Faculty of Science, Department of Geological Sciences.
    Bradley, Raymond S.
    GDGT distribution in a stratified lake and implications for the application of TEX86 in paleoenvironmental reconstructions2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 34465Article in journal (Refereed)
    Abstract [en]

    We investigated the relationship between distributions of GDGTs, GDGT-based proxies and environmental factors in a stratified lake in northwestern Norway. More than 90% of isoGDGTs were produced at the bottom of the oxycline, indicating a predominance of ammonia-oxidizing Group I.1a of Thaumarchaeota, supported by high crenarchaeol/caldarchaeol ratios. Dissolved oxygen content, rather than temperature, exercised a primary control on TEX86 values. In spite of low BIT value in surface sediment, the reconstructed lake surface temperature was cold biased. MBT values in streams and lake surface water were significantly smaller than those in the catchment soil, suggesting in situ production of brGDGTs in streams. A rapid transition of MBT vs. temperature/pH relationships occurring at the bottom of oxycline indicated the differential production of various brGDGTs with D.O. and depths. Only within the oxycline were CBT-based pH values close to in situ pH. Our results confirm earlier studies calling for caution in applying TEX86 as a surface temperature proxy, or MBT and/or CBT for reconstructing pH, in anoxic or euxinic lakes, estuaries and ocean basins. We propose that caldarchaeol/crenarchaeol ratio, an indicator of contributions from methanogenic archaea, together with the BIT and TEX86 proxies, can help reconstruct past levels of stratification.

  • 207. Zhao, Jing
    et al.
    Lee, Sang Hoon
    Huss, Mikael
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Holme, Petter
    The Network Organization of Cancer-associated Protein Complexes in Human Tissues2013In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, article id 1583Article in journal (Refereed)
    Abstract [en]

    Differential gene expression profiles for detecting disease genes have been studied intensively in systems biology. However, it is known that various biological functions achieved by proteins follow from the ability of the protein to form complexes by physically binding to each other. In other words, the functional units are often protein complexes rather than individual proteins. Thus, we seek to replace the perspective of disease-related genes by disease-related complexes, exemplifying with data on 39 human solid tissue cancers and their original normal tissues. To obtain the differential abundance levels of protein complexes, we apply an optimization algorithm to genome-wide differential expression data. From the differential abundance of complexes, we extract tissue- and cancer-selective complexes, and investigate their relevance to cancer. The method is supported by a clustering tendency of bipartite cancer-complex relationships, as well as a more concrete and realistic approach to disease-related proteomics.

2345 201 - 207 of 207
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