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- ItemThe role of methane in future climate strategies: mitigation potentials and climate impacts(Dordrecht [u.a.] : Springer Science + Business Media B.V, 2019) Harmsen, Mathijs; Mathijs, Detlef P.; Bodirsky, Benjamin Leon; Chateau, Jean; Durand-Lasserve, Olivier; Drouet, Laurent; Fricko, Oliver; Fujimori, Shinichiro; Gernaat, David E.H.J.; Hanaoka, Tatsuya; Hilaire, Jérôme; Keramidas, Kimon; Luderer, Gunnar; Moura, Maria Cecilia P.; Sano, Fuminori; Smith, Steven J.; Wada, KenichiThis study examines model-specific assumptions and projections of methane (CH4) emissions in deep mitigation scenarios generated by integrated assessment models (IAMs). For this, scenarios of nine models are compared in terms of sectoral and regional CH4 emission reduction strategies, as well as resulting climate impacts. The models’ projected reduction potentials are compared to sector and technology-specific reduction potentials found in literature. Significant cost-effective and non-climate policy related reductions are projected in the reference case (10–36% compared to a “frozen emission factor” scenario in 2100). Still, compared to 2010, CH4 emissions are expected to rise steadily by 9–72% (up to 412 to 654 Mt CH4/year). Ambitious CO2 reduction measures could by themselves lead to a reduction of CH4 emissions due to a reduction of fossil fuels (22–48% compared to the reference case in 2100). However, direct CH4 mitigation is crucial and more effective in bringing down CH4 (50–74% compared to the reference case). Given the limited reduction potential, agriculture CH4 emissions are projected to constitute an increasingly larger share of total anthropogenic CH4 emissions in mitigation scenarios. Enteric fermentation in ruminants is in that respect by far the largest mitigation bottleneck later in the century with a projected 40–78% of total remaining CH4 emissions in 2100 in a strong (2 °C) climate policy case. © 2019, The Author(s).
- ItemMechanical spectroscopy of retina explants at the protein level employing nanostructured scaffolds(London : Royal Soc. of Chemistry, 2016) Rahman, S. Mayazur; Reichenbach, Andreas; Zink, Mareike; Mayr, Stefan G.Development of neuronal tissue, such as folding of the brain, and formation of the fovea centralis in the human retina are intimately connected with the mechanical properties of the underlying cells and the extracellular matrix. In particular for neuronal tissue as complex as the vertebrate retina, mechanical properties are still a matter of debate due to their relation to numerous diseases as well as surgery, where the tension of the retina can result in tissue detachment during cutting. However, measuring the elasticity of adult retina wholemounts is difficult and until now only the mechanical properties at the surface have been characterized with micrometer resolution. Many processes, however, such as pathological changes prone to cause tissue rupture and detachment, respectively, are reflected in variations of retina elasticity at smaller length scales at the protein level. In the present work we demonstrate that freely oscillating cantilevers composed of nanostructured TiO2 scaffolds can be employed to study the frequency-dependent mechanical response of adult mammalian retina explants at the nanoscale. Constituting highly versatile scaffolds with strong tissue attachment for long-term organotypic culture atop, these scaffolds perform damped vibrations as fingerprints of the mechanical tissue properties that are derived using finite element calculations. Since the tissue adheres to the nanostructures via constitutive proteins on the photoreceptor side of the retina, the latter are stretched and compressed during vibration of the underlying scaffold. Probing mechanical response of individual proteins within the tissue, the proposed mechanical spectroscopy approach opens the way for studying tissue mechanics, diseases and the effect of drugs at the protein level.
- ItemPlatelet Membrane-Coated Nanocarriers Targeting Plaques to Deliver Anti-CD47 Antibody for Atherosclerotic Therapy([Beijing] : China Association for Science and Technology, 2022) Chen, Liang; Zhou, Zhongyi; Hu, Cheng; Maitz, Manfred F.; Yang, Li; Luo, Rifang; Wang, YunbingAtherosclerosis, the principle cause of cardiovascular disease (CVD) worldwide, is mainly characterized by the pathological accumulation of diseased vascular cells and apoptotic cellular debris. Atherogenesis is associated with the upregulation of CD47, a key antiphagocytic molecule that is known to render malignant cells resistant to programmed cell removal, or "efferocytosis." Here, we have developed platelet membrane-coated mesoporous silicon nanoparticles (PMSN) as a drug delivery system to target atherosclerotic plaques with the delivery of an anti-CD47 antibody. Briefly, the cell membrane coat prolonged the circulation of the particles by evading the immune recognition and provided an affinity to plaques and atherosclerotic sites. The anti-CD47 antibody then normalized the clearance of diseased vascular tissue and further ameliorated atherosclerosis by blocking CD47. In an atherosclerosis model established in ApoE-/- mice, PMSN encapsulating anti-CD47 antibody delivery significantly promoted the efferocytosis of necrotic cells in plaques. Clearing the necrotic cells greatly reduced the atherosclerotic plaque area and stabilized the plaques reducing the risk of plaque rupture and advanced thrombosis. Overall, this study demonstrated the therapeutic advantages of PMSN encapsulating anti-CD47 antibodies for atherosclerosis therapy, which holds considerable promise as a new targeted drug delivery platform for efficient therapy of atherosclerosis.
- ItemNERNST: a genetically-encoded ratiometric non-destructive sensing tool to estimate NADP(H) redox status in bacterial, plant and animal systems([London] : Springer Nature, 2023) Molinari, Pamela E.; Krapp, Adriana R.; Weiner, Andrea; Beyer, Hannes M.; Kondadi, Arun Kumar; Blomeier, Tim; López, Melina; Bustos-Sanmamed, Pilar; Tevere, Evelyn; Weber, Wilfried; Reichert, Andreas S.; Calcaterra, Nora B.; Beller, Mathias; Carrillo, Nestor; Zurbriggen, Matias D.NADP(H) is a central metabolic hub providing reducing equivalents to multiple biosynthetic, regulatory and antioxidative pathways in all living organisms. While biosensors are available to determine NADP+ or NADPH levels in vivo, no probe exists to estimate the NADP(H) redox status, a determinant of the cell energy availability. We describe herein the design and characterization of a genetically-encoded ratiometric biosensor, termed NERNST, able to interact with NADP(H) and estimate E NADP(H). NERNST consists of a redox-sensitive green fluorescent protein (roGFP2) fused to an NADPH-thioredoxin reductase C module which selectively monitors NADP(H) redox states via oxido-reduction of the roGFP2 moiety. NERNST is functional in bacterial, plant and animal cells, and organelles such as chloroplasts and mitochondria. Using NERNST, we monitor NADP(H) dynamics during bacterial growth, environmental stresses in plants, metabolic challenges to mammalian cells, and wounding in zebrafish. NERNST estimates the NADP(H) redox poise in living organisms, with various potential applications in biochemical, biotechnological and biomedical research.