| 1. |
- Cronin, M. F., et al.
(författare)
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Developing an Observing Air-Sea Interactions Strategy (OASIS) for the global ocean
- 2022
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Ingår i: Ices Journal of Marine Science. - : Oxford University Press (OUP). - 1054-3139 .- 1095-9289. ; 80:2, s. 367-73
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Tidskriftsartikel (refereegranskat)abstract
- The Observing Air-Sea Interactions Strategy (OASIS) is a new United Nations Decade of Ocean Science for Sustainable Development programme working to develop a practical, integrated approach for observing air-sea interactions globally for improved Earth system (including ecosystem) forecasts, CO2 uptake assessments called for by the Paris Agreement, and invaluable surface ocean information for decision makers. Our "Theory of Change" relies upon leveraged multi-disciplinary activities, partnerships, and capacity strengthening. Recommendations from >40 OceanObs'19 community papers and a series of workshops have been consolidated into three interlinked Grand Ideas for creating #1: a globally distributed network of mobile air-sea observing platforms built around an expanded array of long-term time-series stations; #2: a satellite network, with high spatial and temporal resolution, optimized for measuring air-sea fluxes; and #3: improved representation of air-sea coupling in a hierarchy of Earth system models. OASIS activities are organized across five Theme Teams: (1) Observing Network Design & Model Improvement; (2) Partnership & Capacity Strengthening; (3) UN Decade OASIS Actions; (4) Best Practices & Interoperability Experiments; and (5) Findable-Accessible-Interoperable-Reusable (FAIR) models, data, and OASIS products. Stakeholders, including researchers, are actively recruited to participate in Theme Teams to help promote a predicted, safe, clean, healthy, resilient, and productive ocean.
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| 2. |
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| 3. |
- Gong, Y., et al.
(författare)
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Cytochrome P450 oxidase 2J inhibition suppresses choroidal neovascularization in mice
- 2022
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Ingår i: Metabolism: Clinical and Experimental. - : Elsevier BV. - 0026-0495. ; 134
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Choroidal neovascularization (CNV) in age-related macular degeneration (AMD) leads to blindness. It has been widely reported that increased intake of ω−3 long-chain polyunsaturated fatty acids (LCPUFA) diets reduce CNV. Of the three major pathways metabolizing ω−3 (and ω−6 LCPUFA), the cyclooxygenase and lipoxygenase pathways generally produce pro-angiogenic metabolites from ω−6 LCPUFA and anti-angiogenic ones from ω−3 LCPUFA. Howevehr, cytochrome P450 oxidase (CPY) 2C produces pro-angiogenic metabolites from both ω−6 and ω−3 LCPUFA. The effects of CYP2J2 products on ocular neovascularization are still unknown. Understanding how each metabolic pathway affects the protective effect of ω−3 LCPUFA on retinal neovascularization may lead to therapeutic interventions. Objectives: To investigate the effects of LCPUFA metabolites through CYP2J2 pathway and CYP2J2 regulation on CNV both in vivo and ex vivo. Methods: The impact of CYP2J2 overexpression and inhibition on neovascularization in the laser-induced CNV mouse model was assessed. The plasma levels of CYP2J2 metabolites were measured by liquid chromatography and tandem mass spectroscopy. The choroidal explant sprouting assay was used to investigate the effects of CYP2J2 inhibition and specific LCPUFA CYP2J2 metabolites on angiogenesis ex vivo. Results: CNV was exacerbated in Tie2-Cre CYP2J2-overexpressing mice and was associated with increased levels of plasma docosahexaenoic acids. Inhibiting CYP2J2 activity with flunarizine decreased CNV in both ω−6 and ω−3 LCPUFA-fed wild-type mice. In Tie2-Cre CYP2J2-overexpressing mice, flunarizine suppressed CNV by 33 % and 36 % in ω−6, ω−3 LCPUFA diets, respectively, and reduced plasma levels of CYP2J2 metabolites. The pro-angiogenic role of CYP2J2 was corroborated in the choroidal explant sprouting assay. Flunarizine attenuated ex vivo choroidal sprouting, and 19,20-EDP, a ω−3 LCPUFA CYP2J2 metabolite, increased sprouting. The combined inhibition of CYP2J2 with flunarizine and CYP2C8 with montelukast further enhanced CNV suppression via tumor necrosis factor-α suppression. Conclusions: CYP2J2 inhibition augmented the inhibitory effect of ω−3 LCPUFA on CNV. Flunarizine suppressed pathological choroidal angiogenesis, and co-treatment with montelukast inhibiting CYP2C8 further enhanced the effect. CYP2 inhibition might be a viable approach to suppress CNV in AMD. © 2022 Elsevier Inc.
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| 4. |
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Discussing Bach
- 2020. - 1
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Samlingsverk (redaktörskap) (refereegranskat)abstract
- In this inaugural issue of Discussing Bach panel members propose several new, historically grounded approaches to the question of emotion in Bach’s music, building on some of the frameworks developed in recent emotions history. Conversely, they consider what the study of music (and Bach’s music in particular) might fruitfully contribute to the writing of emotional histories. Each participant presents a short position statement on an aspect of the topic which is then briefly discussed by the others. Bettina Varwig begins by reflecting on the place of music within the history of emotions and the ways in which new approaches to Bach’s music can reshape certain key narratives about early modern affect. Ruth Tatlow then explores the role that musical proportions were understood to play in generating emotional response, illustrating her points from the history of resonating numbers and resonating form. Finally, John Butt considers the emotional content in Bach’s music in terms of concepts of embodiment, specifically the ways in which dance allusions are nested in the music on an astonishing variety of levels.
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| 5. |
- Kubota, Manabu, et al.
(författare)
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Dynamic alterations in the central glutamatergic status following food and glucose intake : in vivo multimodal assessments in humans and animal models
- 2021
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - 0271-678X. ; 41:11, s. 2928-2943
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Tidskriftsartikel (refereegranskat)abstract
- Fluctuations of neuronal activities in the brain may underlie relatively slow components of neurofunctional alterations, which can be modulated by food intake and related systemic metabolic statuses. Glutamatergic neurotransmission plays a major role in the regulation of excitatory tones in the central nervous system, although just how dietary elements contribute to the tuning of this system remains elusive. Here, we provide the first demonstration by bimodal positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) that metabotropic glutamate receptor subtype 5 (mGluR5) ligand binding and glutamate levels in human brains are dynamically altered in a manner dependent on food intake and consequent changes in plasma glucose levels. The brain-wide modulations of central mGluR5 ligand binding and glutamate levels and profound neuronal activations following systemic glucose administration were further proven by PET, MRS, and intravital two-photon microscopy, respectively, in living rodents. The present findings consistently support the notion that food-associated glucose intake is mechanistically linked to glutamatergic tones in the brain, which are translationally accessible in vivo by bimodal PET and MRS measurements in both clinical and non-clinical settings.
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| 6. |
- Tomita, Y., et al.
(författare)
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Free fatty acid receptor 4 activation protects against choroidal neovascularization in mice
- 2020
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Ingår i: Angiogenesis. - : Springer Science and Business Media LLC. - 0969-6970 .- 1573-7209. ; 23, s. 385-394
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Tidskriftsartikel (refereegranskat)abstract
- To examine whether free fatty acid receptor 4 (FFAR4) activation can protect against choroidal neovascularization (CNV), which is a common cause of blindness, and to elucidate the mechanism underlying the inhibition, we used the mouse model of laser-induced CNV to mimic angiogenic aspects of age-related macular degeneration (AMD). Laser-induced CNV was compared between groups treated with an FFAR4 agonist or vehicle, and between FFAR4 wild-type (Ffar4+/+) and knock out (Ffar4−/−) mice on a C57BL/6J/6N background. The ex vivo choroid-sprouting assay, including primary retinal pigment epithelium (RPE) and choroid, without retina was used to investigate whether FFAR4 affects choroidal angiogenesis. Western blotting for pNF-ĸB/NF-ĸB and qRT-PCR for Il-6, Il-1β, Tnf-α, Vegf, and Nf-ĸb were used to examine the influence of FFAR4 on inflammation, known to influence CNV. RPE isolated from Ffar4+/+ and Ffar4−/− mice were used to assess RPE contribution to inflammation. The FFAR4 agonist suppressed laser-induced CNV in C57BL/6J mice, and CNV increased in Ffar4−/− compared to Ffar4+/+ mice. We showed that the FFAR4 agonist acted through the FFAR4 receptor. The FFAR4 agonist suppressed mRNA expression of inflammation markers (Il-6, Il-1β) via the NF-ĸB pathway in the retina, choroid, RPE complex. The FFAR4 agonist suppressed neovascularization in the choroid-sprouting ex vivo assay and FFAR4 deficiency exacerbated sprouting. Inflammation markers were increased in primary RPE cells of Ffar4−/− mice compared with Ffar4+/+ RPE. In this mouse model, the FFAR4 agonist suppressed CNV, suggesting FFAR4 to be a new molecular target to reduce pathological angiogenesis in CNV. © 2020, Springer Nature B.V.
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| 7. |
- Tomita, Y., et al.
(författare)
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Metabolism in Retinopathy of Prematurity
- 2021
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Ingår i: Life-Basel. - : MDPI AG. - 2075-1729. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- Retinopathy of prematurity is defined as retinal abnormalities that occur during development as a consequence of disturbed oxygen conditions and nutrient supply after preterm birth. Both neuronal maturation and retinal vascularization are impaired, leading to the compensatory but uncontrolled retinal neovessel growth. Current therapeutic interventions target the hypoxia-induced neovessels but negatively impact retinal neurons and normal vessels. Emerging evidence suggests that metabolic disturbance is a significant and underexplored risk factor in the disease pathogenesis. Hyperglycemia and dyslipidemia correlate with the retinal neurovascular dysfunction in infants born prematurely. Nutritional and hormonal supplementation relieve metabolic stress and improve retinal maturation. Here we focus on the mechanisms through which metabolism is involved in preterm-birth-related retinal disorder from clinical and experimental investigations. We will review and discuss potential therapeutic targets through the restoration of metabolic responses to prevent disease development and progression.
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| 8. |
- Tomita, Y., et al.
(författare)
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Vitreous metabolomics profiling of proliferative diabetic retinopathy
- 2021
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 64, s. 70-82
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Proliferative diabetic retinopathy (PDR) with retinal neovascularisation (NV) is a leading cause of vision loss. This study identified a set of metabolites that were altered in the vitreous humour of PDR patients compared with non-diabetic control participants. We corroborated changes in vitreous metabolites identified in prior studies and identified novel dysregulated metabolites that may lead to treatment strategies for PDR. Methods We analysed metabolites in vitreous samples from 43 PDR patients and 21 non-diabetic epiretinal membrane control patients from Japan (age 27-80 years) via ultra-high-performance liquid chromatography-mass spectrometry. We then investigated the association of a novel metabolite (creatine) with retinal NV in mouse oxygen-induced retinopathy (OIR). Creatine or vehicle was administered from postnatal day (P)12 to P16 (during induced NV) via oral gavage. P17 retinas were quantified for NV and vaso-obliteration. Results We identified 158 metabolites in vitreous samples that were altered in PDR patients vs control participants. We corroborated increases in pyruvate, lactate, proline and allantoin in PDR, which were identified in prior studies. We also found changes in metabolites not previously identified, including creatine. In human vitreous humour, creatine levels were decreased in PDR patients compared with epiretinal membrane control participants (false-discovery rate <0.001). We validated that lower creatine levels were associated with vascular proliferation in mouse retina in the OIR model (p = 0.027) using retinal metabolomics. Oral creatine supplementation reduced NV compared with vehicle (P12 to P16) in OIR (p = 0.0024). Conclusions/interpretation These results suggest that metabolites from vitreous humour may reflect changes in metabolism that can be used to find pathways influencing retinopathy. Creatine supplementation could be useful to suppress NV in PDR.
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