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- Ramilowski, JA, et al.
(författare)
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Functional annotation of human long noncoding RNAs via molecular phenotyping
- 2020
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Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 30:7, s. 1060-1072
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Tidskriftsartikel (refereegranskat)abstract
- Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-to-date lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.
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| 4. |
- Sorokina, E. S., et al.
(författare)
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Sapphire-bearing magmatic rocks trace the boundary between paleo-continents: A case study of Ilmenogorsky alkaline complex, Uralian collision zone of Russia
- 2021
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Ingår i: Gondwana Research. - : Elsevier BV. - 1342-937X. ; 92, s. 239-252
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Tidskriftsartikel (refereegranskat)abstract
- Metamorphic gem corundum (mainly ruby) deposits are robust indicators of continent-continent collision processes. However, a systematic link of primary magmatic blue sapphire occurrences to orogenic belts is less understood. An example is the Ilmenogorsky alkaline complex, within the Ilmen Mountains region and part of the Uralian orogenic belt. The mobile belt is a product of the collision among Kazakhstania, Laurussia, and Siberia continents prior to the closure of the Paleo-Uralian ocean and formation of the Laurasia supercontinent (330-250 Ma). It is believed that the alkaline complex became included into the separate SysertskIlmenogorsk microcontinent with unconstrained borders, when sandwiched between Kazakhstania and Laurussia during that collision. Paleo-reconstructions illustrate that magmatic and metasomatic sapphire deposits linked to alkaline magmatism trace the natural boundary of the "lost" microcontinent with a high precision. The syenite pegmatites of alkaline complex carried unusually large corundum-blue sapphire megacrysts that have recorded the multi-stage development of the Ilmenogorsky complex. The deposits were formed at about 275-295 Ma ago as reconstructed by in situ LA-ICP-MS U-Pb zircon dating. This formation stage corresponds to a broader continental collision process followed by the formation of Uralian orogeny in the area of the Ilmenogorsky complex. One pegmatite deposit, the "298" mine, is characterized by the occurrence of unusually large corundum megacrysts. The analyses of Rb-Sr isotopic system in the rocks from this deposit revealed two isochrons at 249 +/- 2 Ma and 254 +/- 22 Ma implying a late stage modification of original pegmatites. The timing of this stage corresponds to the limited post-collision stretching time. Hence, corundum-blue sapphire studied from magmatic (syenites) and metasomatic rocks linked to alkaline rocks in Uralian orogen suggests as a promising indicator for constraining the timing of continent-to-continent collision processes. (c) 2021 International Association for Gondwana Research. Published by Elsevier B.V. All rights reserved.
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| 7. |
- Bonetti, A, et al.
(författare)
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RADICL-seq identifies general and cell type-specific principles of genome-wide RNA-chromatin interactions
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 1018-
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Tidskriftsartikel (refereegranskat)abstract
- Mammalian genomes encode tens of thousands of noncoding RNAs. Most noncoding transcripts exhibit nuclear localization and several have been shown to play a role in the regulation of gene expression and chromatin remodeling. To investigate the function of such RNAs, methods to massively map the genomic interacting sites of multiple transcripts have been developed; however, these methods have some limitations. Here, we introduce RNA And DNA Interacting Complexes Ligated and sequenced (RADICL-seq), a technology that maps genome-wide RNA–chromatin interactions in intact nuclei. RADICL-seq is a proximity ligation-based methodology that reduces the bias for nascent transcription, while increasing genomic coverage and unique mapping rate efficiency compared with existing methods. RADICL-seq identifies distinct patterns of genome occupancy for different classes of transcripts as well as cell type–specific RNA-chromatin interactions, and highlights the role of transcription in the establishment of chromatin structure.
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| 8. |
- Krakhmalev, Pavel, 1973-, et al.
(författare)
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Influence of heat treatment under hot isostatic pressing (HIP) on microstructure of intermetallic-reinforced tool steel manufactured by laser powder bed fusion
- 2020
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Ingår i: Materials Science & Engineering A: Structural Materials: Properties, Microstructure and Processing. - : Elsevier BV. - 0921-5093 .- 1873-4936. ; 772
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Tidskriftsartikel (refereegranskat)abstract
- Microstructure and properties of as-built laser powder bed fusion (LPBF) steels differ from the conventional ones, and they may contain some porosity and lack of fusion. Therefore, post-treatments, including hot isostatic pressing (HIP), are used to density the material, and tailor the properties of the final product. Usually, HIP is performed as an operation separate from heat treatment. In the present investigation a new approach was used, in which the whole cycle of the heat treatment was carried out in HIP under pressure, and the influence of HIP on microstructure of an advanced stainless maraging tool steel manufactured by LPBF was investigated. For a comparison, a conventional steel grade of the same chemical composition, after a heat treatment at the same temperature-time conditions, was also characterized. The microstructure of the steel was investigated by means of advanced microscopy and atom probe tomography. The influence of the manufacturing route, heat treatment and HIP on microstructure, austenitic phase fraction and size distribution of precipitates was investigated, and the role of high pressure in stabilization of austenite in the microstructure was discussed. It was concluded that since HIP influences phase transformations, a fundamental understanding of the influence of HIP on microstructure is nececcary, and development of new post processing regimes guaranteeing the best performance of the material is required.
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| 9. |
- Romanova, EI, et al.
(författare)
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RUNX1/CEBPA Mutation in Acute Myeloid Leukemia Promotes Hypermethylation and Indicates for Demethylation Therapy
- 2022
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 23:19
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Tidskriftsartikel (refereegranskat)abstract
- Acute myeloid leukemia (AML) is a rapidly progressing heterogeneous disease with a high mortality rate, which is characterized by hyperproliferation of atypical immature myeloid cells. The number of AML patients is expected to increase in the near future, due to the old-age-associated nature of AML and increased longevity in the human population. RUNX1 and CEBPA, key transcription factors (TFs) of hematopoiesis, are frequently and independently mutated in AML. RUNX1 and CEBPA can bind TET2 demethylase and attract it to their binding sites (TFBS) in cell lines, leading to DNA demethylation of the regions nearby. Since TET2 does not have a DNA-binding domain, TFs are crucial for its guidance to target genomic locations. In this paper, we show that RUNX1 and CEBPA mutations in AML patients affect the methylation of important regulatory sites that resulted in the silencing of several RUNX1 and CEBPA target genes, most likely in a TET2-dependent manner. We demonstrated that hypermethylation of TFBS in AML cells with RUNX1 mutations was associated with resistance to anticancer chemotherapy. Demethylation therapy restored expression of the RUNX1 target gene, BIK, and increased sensitivity of AML cells to chemotherapy. If our results are confirmed, mutations in RUNX1 could be an indication for prescribing the combination of cytotoxic and demethylation therapies.
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