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- Cruz-Gallardo, I., et al.
(författare)
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The binding of TIA-1 to RNA C-rich sequences is driven by its C-terminal RRM domain
- 2014
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Ingår i: Rna Biology. - : Informa UK Limited. - 1547-6286 .- 1555-8584. ; 11:6, s. 766-776
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Tidskriftsartikel (refereegranskat)abstract
- T-cell intracellular antigen-1 (TIA-1) is a key DNA/RNA binding protein that regulates translation by sequestering target mRNAs in stress granules (SG) in response to stress conditions. TIA-1 possesses three RNA recognition motifs (RRM) along with a glutamine-rich domain, with the central domains (RRM2 and RRM3) acting as RNA binding platforms. While the RRM2 domain, which displays high affinity for U-rich RNA sequences, is primarily responsible for interaction with RNA, the contribution of RRM3 to bind RNA as well as the target RNA sequences that it binds preferentially are still unknown. Here we combined nuclear magnetic resonance (NMR) and surface plasmon resonance (SPR) techniques to elucidate the sequence specificity of TIA-1 RRM3. With a novel approach using saturation transfer difference NMR (STD-NMR) to quantify protein-nucleic acids interactions, we demonstrate that isolated RRM3 binds to both C-and U-rich stretches with micromolar affinity. In combination with RRM2 and in the context of full-length TIA-1, RRM3 significantly enhanced the binding to RNA, particularly to cytosine-rich RNA oligos, as assessed by biotinylated RNA pull-down analysis. Our findings provide new insight into the role of RRM3 in regulating TIA-1 binding to C-rich stretches, that are abundant at the 5' TOPs (5' terminal oligopyrimidine tracts) of mRNAs whose translation is repressed under stress situations.
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- Hasan, Shahriar, 1991-, et al.
(författare)
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PlatoonSAFE : An Integrated Simulation Tool for Evaluating Platoon Safety
- 2023
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Ingår i: IEEE Open Journal of Intelligent Transportation Systems. - : Institute of Electrical and Electronics Engineers Inc.. - 2687-7813. ; 4, s. 325-347
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Tidskriftsartikel (refereegranskat)abstract
- Platooning is highly tractable for enabling fuel savings for autonomous and semi-autonomous cars and trucks. Safety concerns are one of the main impediments that need to be overcome before vehicle platoons can be deployed on ordinary roads despite their readily available technical feasibility. Simulation studies remain vital for evaluating platoon safety applications primarily due to the high cost of field tests. To this end, we present PlatoonSAFE, an open-source simulation tool that promotes the simulation studies of fault tolerance in platooning by enabling the monitoring of transient communication outages during runtime and assigning an appropriate performance level as a function of the instantaneous communication quality. In addition, PlatoonSAFE facilitates the simulation of several emergency braking strategies to evaluate their efficacy in transitioning a platoon to a fail-safe state. Furthermore, two Machine Learning (ML) models are integrated into PlatoonSAFE that can be employed as an onboard prediction tool in the platooning vehicles to facilitate online training of ML models and real-time prediction of communication, network, and traffic parameters. In this paper, we present the PlatoonSAFE structure, its features and implementation details, configuration parameters, and evaluation metrics required to evaluate the fault tolerance of platoon safety applications.
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- van der Brug, MP, et al.
(författare)
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RNA binding activity of the recessive parkinsonism protein DJ-1 supports involvement in multiple cellular pathways
- 2008
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 105:29, s. 10244-10249
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease (PD) is a major neurodegenerative condition with several rare Mendelian forms. Oxidative stress and mitochondrial function have been implicated in the pathogenesis of PD but the molecular mechanisms involved in the degeneration of neurons remain unclear. DJ-1 mutations are one cause of recessive parkinsonism, but this gene is also reported to be involved in cancer by promoting Ras signaling and suppressing PTEN-induced apoptosis. The specific function of DJ-1 is unknown, although it is responsive to oxidative stress and may play a role in the maintenance of mitochondria. Here, we show, using four independent methods, that DJ-1 associates with RNA targets in cells and the brain, including mitochondrial genes, genes involved in glutathione metabolism, and members of the PTEN/PI3K cascade. Pathogenic recessive mutants are deficient in this activity. We show that DJ-1 is sufficient for RNA binding at nanomolar concentrations. Further, we show that DJ-1 binds RNA but dissociates after oxidative stress. These data implicate a single mechanism for the pleiotropic effects of DJ-1 in different model systems, namely that the protein binds multiple RNA targets in an oxidation-dependent manner.
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- Fischer, M Dominik, et al.
(författare)
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Expression profiling reveals metabolic and structural components of extraocular muscles
- 2002
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Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 9:2, s. 71-84
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Tidskriftsartikel (refereegranskat)abstract
- The extraocular muscles (EOM) are anatomically and physiologically distinct from other skeletal muscles. EOM are preferentially affected in mitochondrial myopathies, but spared in Duchenne's muscular dystrophy. The anatomical and pathophysiological properties of EOM have been attributed to their unique molecular makeup: an allotype. We used expression profiling to define molecular features of the EOM allotype. We found 346 differentially expressed genes in rat EOM compared with tibialis anterior, based on a twofold difference cutoff. Genes required for efficient, fatigue-resistant, oxidative metabolism were increased in EOM, whereas genes for glycogen metabolism were decreased. EOM also showed increased expression of genes related to structural components of EOM such as vessels, nerves, mitochondria, and neuromuscular junctions. Additionally, genes related to specialized functional roles of EOM such as the embryonic and EOM-specific myosin heavy chains and genes for muscle growth, development, and/or regeneration were increased. The EOM expression profile was validated using biochemical, structural, and molecular methods. Characterization of the EOM expression profile begins to define gene transcription patterns associated with the unique anatomical, metabolic, and pathophysiological properties of EOM.
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