iScience

Journal: iScience

Publisher

Elsevier

ISSN

2589-0042

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Publications 1 - 10 of 48

Islet Macrophages Shift to a Reparative State following Pancreatic Beta-Cell Death and Are a Major Source of Islet Insulin-like Growth Factor-1
Nackiewicz, Dominika; Dan, Meixia; Speck, Madeleine; et al. (2020)
iScience
Macrophages play a dynamic role in tissue repair following injury. Here we found that following streptozotocin (STZ)-induced beta-cell death, mouse islet macrophages had increased Igf1 expression, decreased proinflammatory cytokine expression, and transcriptome changes consistent with macrophages undergoing efferocytosis and having an enhanced state of metabolism. Macrophages were the major, if not sole, contributors to islet insulin-like growth factor-1 (IGF-1) production. Adoptive transfer experiments showed that macrophages can maintain insulin secretion in vivo following beta-cell death with no effects on islet cell turnover. IGF-1 neutralization during STZ treatment decreased insulin secretion without affecting islet cell apoptosis or proliferation. Interestingly, high-fat diet (HFD) combined with STZ further skewed islet macrophages to a reparative state. Finally, islet macrophages from db/db mice also expressed decreased proinflammatory cytokines and increased Igf1 mRNA. These data have important implications for islet biology and pathology and show that islet macrophages preserve their reparative state following beta-cell death even during HFD feeding and severe hyperglycemia.
Building an interdisciplinary program of cardiovascular research at the Swiss Federal Institute of Technology– the ETHeart story
Kourouklis, Andreas P.; Wu, Xi; Geyer, Robin C.; et al. (2022)
iScience
In this backstory, researchers from Swiss Federal Institute of Technology (ETH Zurich) who initiated an interdisciplinary program to generate innovative solutions for different cardiovascular diseases, such as myocardial infarction, valvular replacement, and movement-based rehabilitation therapy, discuss the benefits and challenges of interdisciplinary research.
High Precision of Spike Timing across Olfactory Receptor Neurons Allows Rapid Odor Coding in Drosophila
Egea-Weiss, Alexander; Renner, Alpha; Kleineidam, Christoph J.; et al. (2018)
iScience
In recent years, it has become evident that olfaction is a fast sense, and millisecond short differences in stimulus onsets are used by animals to analyze their olfactory environment. In contrast, olfactory receptor neurons are thought to be relatively slow and temporally imprecise. These observations have led to a conundrum: how, then, can an animal resolve fast stimulus dynamics and smell with high temporal acuity? Using parallel recordings from olfactory receptor neurons in Drosophila, we found hitherto unknown fast and temporally precise odorant-evoked spike responses, with first spike latencies (relative to odorant arrival) down to 3 ms and with a SD below 1 ms. These data provide new upper bounds for the speed of olfactory processing and suggest that the insect olfactory system could use the precise spike timing for olfactory coding and computation, which can explain insects' rapid processing of temporal stimuli when encountering turbulent odor plumes.
High-Throughput Platform for Optoacoustic Probing of Genetically Encoded Calcium Ion Indicators
Hofmann, Urs A.T.; Fabritius, Arne; Rebling, Johannes; et al. (2019)
iScience
Functional optoacoustic (OA) imaging assisted with genetically encoded calcium ion indicators (GECIs) holds promise for imaging large-scale neuronal activity at depths and spatiotemporal resolutions not attainable with existing optical microscopic techniques. However, currently available GECIs optimized for fluorescence (FL) imaging lack sufficient contrast for OA imaging and respond at wavelengths having limited penetration into the mammalian brain. Here we present an imaging platform capable of rapid assessment and cross-validation between OA and FL responses of sensor proteins expressed in Escherichia coli colonies. The screening system features optimized pulsed light excitation combined with ultrasensitive ultrasound detection to mitigate photobleaching while further allowing the dynamic characterization of calcium ion responses with millisecond precision. Targeted probing of up to six individual colonies per second in both calcium-loaded and calcium-unloaded states was possible with the system. The new platform greatly facilitates optimization of absorption-based labels, thus setting the stage for directed evolution of OA GECIs.
Acceptance of meat reduction policies in Switzerland
Richter, Sebastian; Muller, Adrian; Stolze, Mathias; et al. (2023)
iScience
The aim of this study was to analyze the acceptance of different policy measures affecting meat consumption in Switzerland. We conducted qualitative interviews with leading stakeholders and elaborated 37 policy measures for reducing meat consumption. In a standardized survey, we analyzed the acceptance of these measures and important preconditions for their implementation. Measures with potentially the biggest direct leverage, such as a VAT increase on meat products, were highly rejected. We found high levels of acceptance for measures that do not directly affect meat consumption but have the potential for significant changes of meat consumption in the longer run – such as research investment and sustainable diet education. Furthermore, some measures with considerable short-term effects were widely accepted (e.g., stricter animal welfare standards, ban of meat advertisements). These measures could be a promising starting point for policy makers aiming at a transformation of the food system toward lower levels of meat consumption.
Genetic ablation of ketohexokinase C isoform impairs pancreatic cancer development
Guccini, Ilaria; Tang, Guanghui; To, Trang T.; et al. (2023)
iScience
Although dietary fructose is associated with an elevated risk for pancreatic cancer, the underlying mechanisms remain elusive. Here, we report that ketohexokinase (KHK), the rate-limiting enzyme of fructose metabolism, is a driver of PDAC development. We demonstrate that fructose triggers KHK and induces fructolytic gene expression in mouse and human PDAC. Genetic inactivation of KhkC enhances the survival of KPC-driven PDAC even in the absence of high fructose diet. Furthermore, it decreases the viability, migratory capability, and growth of KPC cells in a cell autonomous manner. Mechanistically, we demonstrate that genetic ablation of KHKC strongly impairs the activation of KRAS-MAPK pathway and of rpS6, a downstream target of mTORC signaling. Moreover, overexpression of KHKC in KPC cells enhances the downstream KRAS pathway and cell viability. Our data provide new insights into the role of KHK in PDAC progression and imply that inhibiting KHK could have profound implications for pancreatic cancer therapy.
The impact of open access mandates on scientific research and technological development in the U.S.
Probst, Benedict; Lohmann, Paul M.; Kontoleon, Andreas; et al. (2023)
iScience
Getting to a net-zero emissions economy requires faster development and diffusion of novel clean energy technologies. We exploit a rare natural experiment to study the impact of an open-access mandate on the diffusion of scientific research into patented technologies. From 2014 onwards, the U.S. Department of Energy (DOE) required its 17 National Laboratories (NLs) to publish all peer-reviewed scientific articles without a paywall. Using data from more than 300,000 scientific publications between 2012 and 2018, we show that scientific articles subject to the mandate were used on average 42% more in patents, despite embargo periods of up to 12 months. We also show that articles subject to the mandate were not cited more frequently by other academic articles. Our findings suggest that the mandate primarily contributed to technological development but has not led to additional academic research. Lastly, we show that small firms were the primary beneficiaries of the increased diffusion of scientific knowledge.
Mind the goal: Trade-offs between flexibility goals for controlled electric vehicle charging strategies
Gschwendtner, Christine; Knoeri, Christof; Stephan, Annegret (2023)
iScience
Electrification is one of the main decarbonization strategies for transportation. While uncontrolled electric vehicle (EV) charging can challenge the electricity system, controlled EV charging can offer flexibility. Using an agent-based model, we simulate combinations of two elements of EV charging, plug-in behaviors and controlled-charging processes, and measure flexibility goals with four metrics: total load shift, increase in midday load, peak reduction, and flatness of the load curve. We reveal trade-offs between these flexibility goals, which indicate that the most beneficial combinations are specific to spatial areas and their flexibility goals. Furthermore, we find that controlled-charging processes show higher impact on the flexibility metrics than plug-in behaviors, particularly with high EV and charging-station diffusion, but less so in rural areas. Incentivizing beneficial combinations can increase the flexibility potential of EV charging and potentially avoid grid reinforcements.
Collaborative and selfish mitigation strategies to tackle energy scarcity: The case of the European gas crisis
Mannhardt, Jacob; Gabrielli, Paolo; Sansavini, Giovanni (2023)
iScience
Following the disruption of Russian natural gas flows to Europe, we investigate the impact of collaborative and selfish behavior of European countries to tackle energy scarcity and supply electricity, heat, and industrial gas to end users. We study how the operation of the European energy system will need to adapt to the disruption and identify optimal strategies to overcome the unavailability of Russian gas. Those strategies include diversifying gas imports, shifting energy generation to non-gas-based technologies, and reducing energy demands. Findings suggest that: (1) selfish behavior of Central European countries exacerbates the energy scarcity for many Southeastern European countries; (2) proactive collaborative energy savings, together with a mild winter, can fully relieve the stress of the gas shortage; (3) diversification of gas imports leads to bottlenecks in the gas network, especially in Southeastern Europe; and (4) electricity generation is mostly shifted to coal-based power plants, causing higher carbon emissions.
De novo peptide grafting to a self-assembling nanocapsule yields a hepatocyte growth factor receptor agonist
Komatsu, Yamato; Terasaka, Naohiro; Sakai, Katsuya; et al. (2021)
iScience
Lasso-grafting (LG) technology is a method for generating de novo biologics (neobiologics) by genetically implanting macrocyclic peptide pharmacophores, which are selected in vitro against a protein of interest, into loops of arbitrary protein scaffolds. In this study, we have generated a neo-capsid that potently binds the hepatocyte growth factor receptor MET by LG of anti-MET peptide pharmacophores into a circularly permuted variant of Aquifex aeolicus lumazine synthase (AaLS), a self-assembling protein nanocapsule. By virtue of displaying multiple-pharmacophores on its surface, the neo-capsid can induce dimerization (or multimerization) of MET, resulting in phosphorylation and endosomal internalization of the MET-capsid complex. This work demonstrates the potential of the LG technology as a synthetic biology approach for generating capsid-based neobiologics capable of activating signaling receptors.

Publications 1 - 10 of 48

Journal: iScience

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