90 research outputs found

    Membrane Tension Gates ERK-Mediated Regulation of Pluripotent Cell Fate

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    Cell fate transitions are frequently accompanied by changes in cell shape and mechanics. However, how cellular mechanics affects the instructive signaling pathways controlling cell fate is poorly understood. To probe the interplay between shape, mechanics, and fate, we use mouse embryonic stem cells (ESCs), which change shape as they undergo early differentiation. We find that shape change is regulated by a b-cateninmediated decrease in RhoA activity and subsequent decrease in the plasma membrane tension. Strikingly, preventing a decrease in membrane tension results in early differentiation defects in ESCs and gastruloids. Decreased membrane tension facilitates the endocytosis of FGF signaling components, which activate ERK signaling and direct the exit from the ESC state. Increasing Rab5a-facilitated endocytosis rescues defective early differentiation. Thus, we show that a mechanically triggered increase in endocytosis regulates early differentiation. Our findings are of fundamental importance for understanding how cell mechanics regulates biochemical signaling and therefore cell fate

    Fluctuation-Based Super-Resolution Traction Force Microscopy

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    Cellular mechanics play a crucial role in tissue homeostasis and are often misregulated in disease. Traction force microscopy is one of the key methods that has enabled researchers to study fundamental aspects of mechanobiology; however, traction force microscopy is limited by poor resolution. Here, we propose a simplified protocol and imaging strategy that enhances the output of traction force microscopy by increasing i) achievable bead density and ii) the accuracy of bead tracking. Our approach relies on super-resolution microscopy, enabled by fluorescence fluctuation analysis. Our pipeline can be used on spinning-disk confocal or widefield microscopes and is compatible with available analysis software. In addition, we demonstrate that our workflow can be used to gain biologically relevant information and is suitable for fast long-term live measurement of traction forces even in light-sensitive cells. Finally, using fluctuation-based traction force microscopy, we observe that filopodia align to the force field generated by focal adhesions

    Anodic and Cathodic Platinum Dissolution Processes Involve Different Oxide Species

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    The degradation of Pt-containing oxygen reduction catalysts for fuel cell applications is strongly linked to the electrochemical surface oxidation and reduction of Pt. Here, we study the surface restructuring and Pt dissolution mechanisms during oxidation/reduction for the case of Pt(100) in 0.1 M HClO4 by combining operando high-energy surface X-ray diffraction, online mass spectrometry, and density functional theory. Our atomic-scale structural studies reveal that anodic dissolution, detected during oxidation, and cathodic dissolution, observed during the subsequent reduction, are linked to two different oxide phases. Anodic dissolution occurs predominantly during nucleation and growth of the first, stripe-like oxide. Cathodic dissolution is linked to a second, amorphous Pt oxide phase that resembles bulk PtO2 and starts to grow when the coverage of the stripe-like oxide saturates. In addition, we find the amount of surface restructuring after an oxidation/reduction cycle to be potential-independent after the stripe-like oxide has reached its saturation coverage.Funding is acknowledged from Deutsche Forschungsgemeinschaft for OMM and SC (project number 418603497), for OMM by the German Federal Ministry of Education and Research (BMBF) via project 05K19FK3, and for DAH by the NSERC (grant RGPIN-2017-04045). FCV acknowledges that the grants PID2021-127957NB-I00 and TED2021-132550B-C21 were funded by MCIN/AEI/ 10.13039/501100011033 and by the European Union. The use of supercomputing facilities at SURFsara was sponsored by NWO Physical Sciences, with financial support by NWO. Open Access funding enabled and organized by Projekt DEAL

    Challenges and new beginnings: Priorities for the EU’s new leadership. EPC Challenge Europe Issue 22, September 2014

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    Table of contents - State of the Union and key challenges for Europe's future, Janis A. Emmanouilidis and Paul Ivan; Europe’s economic challenges and the importance of ideas and innovation, Herman Van Rompuy; The growth challenge for Europe and the EMU, George Pagoulatos; Strengthening the euro area, Daniela Schwarzer; Social Europe. Can the EU again improve people's life prospects?, László Andor; Solidarity and cohesion, Pawel Swieboda; The single market and competitiveness – the challenges for the Juncker team, Malcolm Harbour; A European response to the resource and climate challenge, Jo Leinen; Renewal through international action? Options for EU foreign policy, Rosa Balfour; EU migration policy – new realities, new opportunities, Cecilia Malmström; Freedom of movement of persons – the building-block of European growth, Radoslaw Sikorski; Building up European leadership – an assessment of the recent process, Maria João Rodrigues; Populism in the EU: new threats to the open society?, Heather Grabbe; Differentiated Europe needs strong institutions, Alexander Stubb; Improving decision-making in the EU, Fabian Zuleeg; The need for a New Pact, Janis A. Emmanouilidis

    Research productivity and academics’ conceptions of research

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    This paper asks the question: do people with different levels of research productivity and identification as a researcher think of research differently? It discusses a study that differentiated levels of research productivity among English and Australian academics working in research-intensive environments in three broad discipline areas: science, engineering and technology; social science and humanities; and medicine and health sciences. The paper explores the different conceptions of research held by these academics in terms of their levels of research productivity, their levels of research training, whether they considered themselves an active researcher and a member of a research team, and their disciplinary differences

    High frequency alternating current light-emitting diodes using Langmuir-Blodgett films

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    Alternating current (AC) light emitting diodes (LEDs) have been fabricated where Langmuir-Blodgett (LB) films of quinquethiophene (QT) or poly(3-hexylthiophene) (PHT) have been used as the active material sandwiched between insulating LB layers of poly(methylmethacrylate) (PMMA) or emeraldine base polyaniline (PANI), respectively. The frequency response of the devices has been studied, and as the frequency limit of operation we have used the -3 dB frequency. We have shown that high frequency AC LEDs can be fabricated with as few as 10-15 LB layers of the active material. Electroluminescence (EL) is observed almost equal in intensity in both biases for PMMA/QT/PMMA devices. The EL spectrum for these devices shows a broadening to the low-energy side as compared with the photoluminescence (PL) spectrum. The role of the interfaces for the frequency response is discussed

    Light-emitting diodes using quinquethiophene Langmuir-Blodgett films: effect of electron-transporting layers

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    Langmuir-Blodgett (LB) films of quinquethiophene have been used as active emitting layers to fabricate light-emitting diodes. Green electroluminescence was visible in a dark room. The effect of the thickness of the film on the electroluminescence efficiency has been investigated. Even 5 LB layers have been shown to yield the same luminance as thicker films. Additional LB films of electron-transporting material have been used to increase the quantum efficiency, which has also resulted in a lower "turn-on" current for the device. The electroluminescence spectrum showed a profile identical to the photoluminescence spectrum of quinquethiophene
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