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- Clark, M. S., et al.
(författare)
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Multi-omics for studying and understanding polar life
- 2023
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Ingår i: Nature Communications. - : NATURE PORTFOLIO. - 2041-1723. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Polar ecosystems are experiencing amongst the most rapid rates of regional warming on Earth. Here, we discuss ‘omics’ approaches to investigate polar biodiversity, including the current state of the art, future perspectives and recommendations. We propose a community road map to generate and more fully exploit multi-omics data from polar organisms. These data are needed for the comprehensive evaluation of polar biodiversity and to reveal how life evolved and adapted to permanently cold environments with extreme seasonality. We argue that concerted action is required to mitigate the impact of warming on polar ecosystems via conservation efforts, to sustainably manage these unique habitats and their ecosystem services, and for the sustainable bioprospecting of novel genes and compounds for societal gain.
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| 4. |
- Kajdic, P., et al.
(författare)
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ULF Wave Transmission Across Collisionless Shocks : 2.5D Local Hybrid Simulations
- 2021
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Ingår i: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 126:11
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Tidskriftsartikel (refereegranskat)abstract
- We study the interaction of upstream ultralow frequency (ULF) waves with collisionless shocks by analyzing the outputs of 11 2D local hybrid simulation runs. Our simulated shocks have Alfvenic Mach numbers between 4.29 and 7.42 and their theta BN angles are 15 degrees, 30 degrees, 45 degrees, and 50 degrees. The ULF wave foreshocks develop upstream of all of them. The wavelength and the amplitude of the upstream waves exhibit a complex dependence on the shock's MA and theta BN. The wavelength positively correlates with both parameters, with the dependence on theta BN being much stronger. The amplitude of the ULF waves is proportional to the product of the reflected beam velocity and density, which also depend on MA and theta BN. The interaction of the ULF waves with the shock causes large-scale (several tens of upstream ion inertial lengths) shock rippling. The properties of the shock ripples are related to the ULF wave properties, namely their wavelength and amplitude. In turn, the ripples have a large impact on the ULF wave transmission across the shock because they change local shock properties (theta BN, strength), so that different sections of the same ULF wavefront encounter shock with different characteristics. Downstream fluctuations do not resemble the upstream waves in terms the wavefront extension, orientation or their wavelength. However, some features are conserved in the Fourier spectra of downstream compressive waves that present a bump or flattening at wavelengths approximately corresponding to those of the upstream ULF waves. In the transverse downstream spectra, these features are weaker.
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- Batra, Gorav, et al.
(författare)
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Biomarker-Based Prediction of Recurrent Ischemic Events in Patients With Acute Coronary Syndromes
- 2022
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 80:18, s. 1735-1747
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In patients with acute coronary syndrome (ACS), there is residual and variable risk of recurrent ischemic events.OBJECTIVES: This study aimed to develop biomarker-based prediction models for 1-year risk of cardiovascular (CV) death and myocardial infarction (MI) in patients with ACS undergoing percutaneous coronary intervention.METHODS: We included 10,713 patients from the PLATO (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome) trial in the development cohort and externally validated in 3,508 patients from the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) trial. Variables contributing to risk of CV death/MI were assessed using Cox regression models, and a score was derived using subsets of variables approximating the full model.RESULTS: There were 632 and 190 episodes of CV death/MI in the development and validation cohorts. The most important predictors of CV death/MI were the biomarkers, growth differentiation factor 15, and N-terminal pro-B-type natriuretic peptide, which had greater prognostic value than all candidate variables. The final model included 8 items: age (A), biomarkers (B) (growth differentiation factor 15 and N-terminal pro-B-type natriuretic peptide), and clinical variables (C) (extent of coronary artery disease, previous vascular disease, Killip class, ACS type, P2Y12 inhibitor). The model, named ABC-ACS ischemia, was well calibrated and showed good discriminatory ability for 1-year risk of CV death/MI with C-indices of 0.71 and 0.72 in the development and validation cohorts, respectively. For CV death, the score performed better, with C-indices of 0.80 and 0.84 in the development and validation cohorts, respectively.CONCLUSIONS: An 8-item score for the prediction of CV death/MI was developed and validated for patients with ACS undergoing percutaneous coronary intervention. The ABC-ACS ischemia score showed good calibration and discrimination and might be useful for risk prediction and decision support in patients with ACS. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872; Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Participants With Acute Coronary Syndrome [TRACER]; NCT00527943)
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- Johlander, Andreas, 1990-, et al.
(författare)
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Ion Acceleration Efficiency at the Earth's Bow Shock : Observations and Simulation Results
- 2021
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 914:2
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Tidskriftsartikel (refereegranskat)abstract
- Collisionless shocks are some of the most efficient particle accelerators in heliospheric and astrophysical plasmas. Here we study and quantify ion acceleration at Earth's bow shock with observations from NASA's Magnetospheric Multiscale (MMS) satellites and in a global hybrid-Vlasov simulation. From the MMS observations, we find that quasiparallel shocks are more efficient at accelerating ions. There, up to 15% of the available energy goes into accelerating ions above 10 times their initial energy. Above a shock-normal angle of similar to 50 degrees, essentially no energetic ions are observed downstream of the shock. We find that ion acceleration efficiency is significantly lower when the shock has a low Mach number (M ( A ) < 6) while there is little Mach number dependence for higher values. We also find that ion acceleration is lower on the flanks of the bow shock than at the subsolar point regardless of the Mach number. The observations show that a higher connection time of an upstream field line leads to somewhat higher acceleration efficiency. To complement the observations, we perform a global hybrid-Vlasov simulation with realistic solar-wind parameters with the shape and size of the bow shock. We find that the ion acceleration efficiency in the simulation shows good quantitative agreement with the MMS observations. With the combined approach of direct spacecraft observations, we quantify ion acceleration in a wide range of shock angles and Mach numbers.
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| 7. |
- Kontos, C, et al.
(författare)
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Designed CXCR4 mimic acts as a soluble chemokine receptor that blocks atherogenic inflammation by agonist-specific targeting
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 5981-
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Tidskriftsartikel (refereegranskat)abstract
- Targeting a specific chemokine/receptor axis in atherosclerosis remains challenging. Soluble receptor-based strategies are not established for chemokine receptors due to their discontinuous architecture. Macrophage migration-inhibitory factor (MIF) is an atypical chemokine that promotes atherosclerosis through CXC-motif chemokine receptor-4 (CXCR4). However, CXCR4/CXCL12 interactions also mediate atheroprotection. Here, we show that constrained 31-residue-peptides (‘msR4Ms’) designed to mimic the CXCR4-binding site to MIF, selectively bind MIF with nanomolar affinity and block MIF/CXCR4 without affecting CXCL12/CXCR4. We identify msR4M-L1, which blocks MIF- but not CXCL12-elicited CXCR4 vascular cell activities. Its potency compares well with established MIF inhibitors, whereas msR4M-L1 does not interfere with cardioprotective MIF/CD74 signaling. In vivo-administered msR4M-L1 enriches in atherosclerotic plaques, blocks arterial leukocyte adhesion, and inhibits atherosclerosis and inflammation in hyperlipidemic Apoe−/− mice in vivo. Finally, msR4M-L1 binds to MIF in plaques from human carotid-endarterectomy specimens. Together, we establish an engineered GPCR-ectodomain-based mimicry principle that differentiates between disease-exacerbating and -protective pathways and chemokine-selectively interferes with atherosclerosis.
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| 8. |
- Takahashi, Kazue, et al.
(författare)
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Propagation of Ultralow-Frequency Waves from the Ion Foreshock into the Magnetosphere During the Passage of a Magnetic Cloud
- 2021
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Ingår i: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 126:2
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Tidskriftsartikel (refereegranskat)abstract
- We have examined the properties of ultralow-frequency (ULF) waves in space (the ion foreshock, magnetosheath, and magnetosphere) and at dayside magnetometer stations (L = 1.6-6.5) during Earth's encounter with a magnetic cloud in the solar wind, which is characterized by magnetic fields with large magnitudes (similar to 14 nT) and small cone angles (similar to 30 degrees). In the foreshock, waves were excited at similar to 90 m Hz as expected from theory, but there were oscillations at other frequencies as well. Oscillations near 90 mHz were detected at the other locations in space, but they were not in general the most dominant oscillations. On the ground, pulsations in the approximate Pc2-Pc4 band (5 mHz-120 mHz) were continuously detected at all stations, with no outstanding spectral peaks near 90 mHz in the H component except at stations where the frequency of the third harmonic of standing Alfven waves had this frequency. The fundamental toroidal wave frequency was below 90 mHz at all stations. In the D component spectra, a minor spectral peak is found near 90 mHz at stations located at L < 3, and the power dropped abruptly above this frequency. Magnetospheric compressional wave power was much weaker on the nightside. A hybrid-Vlasov simulation indicates that foreshock ULF waves have short spatial scale lengths and waves transmitted into the magnetosphere are strongly attenuated away from noon.
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| 9. |
- Turc, L., et al.
(författare)
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Transmission of foreshock waves through Earth's bow shock
- 2023
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Ingår i: Nature Physics. - : Springer Nature. - 1745-2473 .- 1745-2481. ; 19:1, s. 78-86
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Tidskriftsartikel (refereegranskat)abstract
- The Earth's magnetosphere and its bow shock, which is formed by the interaction of the supersonic solar wind with the terrestrial magnetic field, constitute a rich natural laboratory enabling in situ investigations of universal plasma processes. Under suitable interplanetary magnetic field conditions, a foreshock with intense wave activity forms upstream of the bow shock. So-called 30 s waves, named after their typical period at Earth, are the dominant wave mode in the foreshock and play an important role in modulating the shape of the shock front and affect particle reflection at the shock. These waves are also observed inside the magnetosphere and down to the Earth's surface, but how they are transmitted through the bow shock remains unknown. By combining state-of-the-art global numerical simulations and spacecraft observations, we demonstrate that the interaction of foreshock waves with the shock generates earthward-propagating, fast-mode waves, which reach the magnetosphere. These findings give crucial insight into the interaction of waves with collisionless shocks in general and their impact on the downstream medium.
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| 10. |
- Zhang, W, et al.
(författare)
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INKILN is a novel long noncoding RNA promoting vascular smooth muscle inflammation via scaffolding MKL1 and USP10
- 2023
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Ingår i: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundActivation of vascular smooth muscle cells (VSMCs) inflammation is vital to initiate vascular disease. However, the role of human-specific long noncoding RNAs (lncRNAs) in VSMC inflammation is poorly understood.MethodsBulk RNA-seq in differentiated human VSMCs revealed a novel human-specific lncRNA calledINflammatory MKL1InteractingLongNoncoding RNA (INKILN).INKILNexpression was assessed in multiple in vitro and ex vivo models of VSMC phenotypic modulation and human atherosclerosis and abdominal aortic aneurysm (AAA) samples. The transcriptional regulation ofINKILNwas determined through luciferase reporter system and chromatin immunoprecipitation assay. Both loss- and gain-of-function approaches and multiple RNA-protein and protein-protein interaction assays were utilized to uncover the role ofINKILNin VSMC proinflammatory gene program and underlying mechanisms. Bacterial Artificial Chromosome (BAC) transgenic (Tg) mice were utilized to studyINKLINexpression and function in ligation injury-induced neointimal formation.ResultsINKILNexpression is downregulated in contractile VSMCs and induced by human atherosclerosis and abdominal aortic aneurysm.INKILNis transcriptionally activated by the p65 pathway, partially through a predicted NF-κB site within its proximal promoter.INKILNactivates the proinflammatory gene expression in cultured human VSMCs and ex vivo cultured vessels. Mechanistically,INKILNphysically interacts with and stabilizes MKL1, a key activator of VSMC inflammation through the p65/NF-κB pathway.INKILNdepletion blocks ILIβ-induced nuclear localization of both p65 and MKL1. Knockdown ofINKILNabolishes the physical interaction between p65 and MKL1, and the luciferase activity of an NF-κB reporter. Further,INKILNknockdown enhances MKL1 ubiquitination, likely through the reduced physical interaction with the deubiquitinating enzyme, USP10.INKILNis induced in injured carotid arteries and exacerbates ligation injury-induced neointimal formation in BAC Tg mice.ConclusionsThese findings elucidate an important pathway of VSMC inflammation involving anINKILN/MKL1/USP10 regulatory axis. Human BAC Tg mice offer a novel and physiologically relevant approach for investigating human-specific lncRNAs under vascular disease conditions.
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