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Sökning: WFRF:(Morgunova E)

  • Resultat 1-33 av 33
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  • Librado, P., et al. (författare)
  • The origins and spread of domestic horses from the Western Eurasian steppes
  • 2021
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 598, s. 634-640
  • Tidskriftsartikel (refereegranskat)abstract
    • Analysis of 273 ancient horse genomes reveals that modern domestic horses originated in the Western Eurasian steppes, especially the lower Volga-Don region. Domestication of horses fundamentally transformed long-range mobility and warfare(1). However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling(2-4) at Botai, Central Asia around 3500 bc(3). Other longstanding candidate regions for horse domestication, such as Iberia(5) and Anatolia(6), have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 bc, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association(7) between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 bc(8,9) driving the spread of Indo-European languages(10). This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium bc Sintashta culture(11,12).
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  • Kaasinen, E, et al. (författare)
  • Impact of constitutional TET2 haploinsufficiency on molecular and clinical phenotype in humans
  • 2019
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1252-
  • Tidskriftsartikel (refereegranskat)abstract
    • Clonal hematopoiesis driven by somatic heterozygous TET2 loss is linked to malignant degeneration via consequent aberrant DNA methylation, and possibly to cardiovascular disease via increased cytokine and chemokine expression as reported in mice. Here, we discover a germline TET2 mutation in a lymphoma family. We observe neither unusual predisposition to atherosclerosis nor abnormal pro-inflammatory cytokine or chemokine expression. The latter finding is confirmed in cells from three additional unrelated TET2 germline mutation carriers. The TET2 defect elevates blood DNA methylation levels, especially at active enhancers and cell-type specific regulatory regions with binding sequences of master transcription factors involved in hematopoiesis. The regions display reduced methylation relative to all open chromatin regions in four DNMT3A germline mutation carriers, potentially due to TET2-mediated oxidation. Our findings provide insight into the interplay between epigenetic modulators and transcription factor activity in hematological neoplasia, but do not confirm the putative role of TET2 in atherosclerosis.
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  • Jolma, A, et al. (författare)
  • Binding specificities of human RNA-binding proteins toward structured and linear RNA sequences
  • 2020
  • Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 30:7, s. 962-973
  • Tidskriftsartikel (refereegranskat)abstract
    • RNA-binding proteins (RBPs) regulate RNA metabolism at multiple levels by affecting splicing of nascent transcripts, RNA folding, base modification, transport, localization, translation, and stability. Despite their central role in RNA function, the RNA-binding specificities of most RBPs remain unknown or incompletely defined. To address this, we have assembled a genome-scale collection of RBPs and their RNA-binding domains (RBDs) and assessed their specificities using high-throughput RNA-SELEX (HTR-SELEX). Approximately 70% of RBPs for which we obtained a motif bound to short linear sequences, whereas ∼30% preferred structured motifs folding into stem–loops. We also found that many RBPs can bind to multiple distinctly different motifs. Analysis of the matches of the motifs in human genomic sequences suggested novel roles for many RBPs. We found that three cytoplasmic proteins—ZC3H12A, ZC3H12B, and ZC3H12C—bound to motifs resembling the splice donor sequence, suggesting that these proteins are involved in degradation of cytoplasmic viral and/or unspliced transcripts. Structural analysis revealed that the RNA motif was not bound by the conventional C3H1 RNA-binding domain of ZC3H12B. Instead, the RNA motif was bound by the ZC3H12B's PilT N terminus (PIN) RNase domain, revealing a potential mechanism by which unconventional RBDs containing active sites or molecule-binding pockets could interact with short, structured RNA molecules. Our collection containing 145 high-resolution binding specificity models for 86 RBPs is the largest systematic resource for the analysis of human RBPs and will greatly facilitate future analysis of the various biological roles of this important class of proteins.
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  • Morgunova, E, et al. (författare)
  • Structural insight into the complex formation of latent matrix metalloproteinase 2 with tissue inhibitor of metalloproteinase 2
  • 2002
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 99:11, s. 7414-7419
  • Tidskriftsartikel (refereegranskat)abstract
    • Matrix metalloproteinases (MMPs) are a family of multidomain enzymes involved in the physiological degradation of connective tissue, as well as in pathological states such as tumor invasion and arthritis. Apart from transcriptional regulation, MMPs are controlled by proenzyme activation and a class of specific tissue inhibitors of metalloproteinases (TIMPs) that bind to the catalytic site. TIMP-2 is a potent inhibitor of MMPs, but it has also been implicated in a unique cell surface activation mechanism of latent MMP-2/gelatinase A/type IV collagenase (proMMP-2), through its binding to the hemopexin domain of proMMP-2 on the one hand and to a membrane-type MMP activator on the other. The present crystal structure of the human proMMP-2/TIMP-2 complex reveals an interaction between the hemopexin domain of proMMP-2 and the C-terminal domain of TIMP-2, leaving the catalytic site of MMP-2 and the inhibitory site of TIMP-2 distant and spatially isolated. The interfacial contact of these two proteins is characterized by two distinct binding regions composed of alternating hydrophobic and hydrophilic interactions. This unique structure provides information for how specificity for noninhibitory MMP/TIMP complex formation is achieved.
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  • Morgunova, E, et al. (författare)
  • Structure of human pro-matrix metalloproteinase-2: activation mechanism revealed
  • 1999
  • Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 284:5420, s. 1667-1670
  • Tidskriftsartikel (refereegranskat)abstract
    • Matrix metalloproteinases (MMPs) catalyze extracellular matrix degradation. Control of their activity is a promising target for therapy of diseases characterized by abnormal connective tissue turnover. MMPs are expressed as latent proenzymes that are activated by proteolytic cleavage that triggers a conformational change in the propeptide (cysteine switch). The structure of proMMP-2 reveals how the propeptide shields the catalytic cleft and that the cysteine switch may operate through cleavage of loops essential for propeptide stability.
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  • Morgunova, M., et al. (författare)
  • The changing geopolitical scope around Arctic offshore petroleum resources : Part 1: Focus on investments
  • 2014
  • Ingår i: World Petroleum Congress Proceedings. - : Energy Institute. - 9781510825673 ; , s. 4324-4329
  • Konferensbidrag (refereegranskat)abstract
    • Latest oil and gas technologies, high oil prices and global climate change make the international business community and oil & gas companies explore distant hard accessible regions such as the Arctic[1], which is characterized by huge hydrocarbon resource potential[2], and can help our society to find a solution for escalating demand for energy. The importance of Arctic petroleum resources goes beyond the regional and national economies. Many consider the Arctic to be the last large petroleum frontier outside the OPEC cartel.[3] Thus geopolitical status of the Arctic is the subject for international game. The paper gives deeper insight into the interconnected and globalized topic of petroleum development in the Arctic region, provides better understanding of up-to-date trends, politics and international relations through the prospect of economic opportunity, which is the strongest driver for the new attention that the Arctic is receiving[4] , especially in the presence of economic and strategic interests, opening of areas by governments for industry exploration and public engagement. A complex series of steps and guidelines is suggested for peaceful, mutually advantageous and successful cooperation of the actors in the Arctic region in the nearest future, because the challenges will be even higher.
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  • Resultat 1-33 av 33

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