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Now showing 1 - 10 of 17
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    Reply to Smith et al.: Social tipping dynamics in a world constrained by conflicting interests
    (Washington, DC : National Acad. of Sciences, 2020) Otto, Ilona M.; Donges, Jonathan F.; Lucht, Wolfgang; Schellnhuber, Hans Joachim
    [No abstract available]
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    Exploring functional pairing between surface glycoconjugates and human galectins using programmable glycodendrimersomes
    (Washington, DC : National Acad. of Sciences, 2018) Xiao, Qi; Ludwig, Anna-Kristin; Romanò, Cecilia; Buzzacchera, Irene; Sherman, Samuel E.; Vetro, Maria; Vértesy, Sabine; Kaltner, Herbert; Reed, Ellen H.; Möller, Martin; Wilson, Christopher J.; Hammer, Daniel A.; Oscarson, Stefan; Klein, Michael L.; Gabius, Hans-Joachim; Percec, Virgil
    Precise translation of glycan-encoded information into cellular activity depends critically on highly specific functional pairing between glycans and their human lectin counter receptors. Sulfoglycolipids, such as sulfatides, are important glycolipid components of the biological membranes found in the nervous and immune systems. The optimal molecular and spatial design aspects of sulfated and nonsulfated glycans with high specificity for lectin-mediated bridging are unknown. To elucidate how different molecular and spatial aspects combine to ensure the high specificity of lectin-mediated bridging, a bottom-up toolbox is devised. To this end, negatively surface-charged glycodendrimersomes (GDSs), of different nanoscale dimensions, containing sulfo-lactose groups are self-assembled in buffer from a synthetic sulfatide mimic: Janus glycodendrimer (JGD) containing a 3′-O-sulfo-lactose headgroup. Also prepared for comparative analysis are GDSs with nonsulfated lactose, a common epitope of human membranes. These self-assembled GDSs are employed in aggregation assays with 15 galectins, comprising disease-related human galectins, and other natural and engineered variants from four families, having homodimeric, heterodimeric, and chimera architectures. There are pronounced differences in aggregation capacity between human homodimeric and heterodimeric galectins, and also with respect to their responsiveness to the charge of carbohydrate-derived ligand. Assays reveal strong differential impact of ligand surface charge and density, as well as lectin concentration and structure, on the extent of surface cross-linking. These findings demonstrate how synthetic JGD-headgroup tailoring teamed with protein engineering and network assays can help explain how molecular matchmaking operates in the cellular context of glycan and lectin complexity.
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    Emergent inequality and business cycles in a simple behavioral macroeconomic model
    (Washington, DC : National Acad. of Sciences, 2021) Asano, Yuki M.; Kolb, Jakob J.; Heitzig, Jobst; Farmer, J. Doyne
    Standard macroeconomic models assume that households are rational in the sense that they are perfect utility maximizers and explain economic dynamics in terms of shocks that drive the economy away from the steady state. Here we build on a standard macroeconomic model in which a single rational representative household makes a savings decision of how much to consume or invest. In our model, households are myopic boundedly rational heterogeneous agents embedded in a social network. From time to time each household updates its savings rate by copying the savings rate of its neighbor with the highest consumption. If the updating time is short, the economy is stuck in a poverty trap, but for longer updating times economic output approaches its optimal value, and we observe a critical transition to an economy with irregular endogenous oscillations in economic output, resembling a business cycle. In this regime households divide into two groups: poor households with low savings rates and rich households with high savings rates. Thus, inequality and economic dynamics both occur spontaneously as a consequence of imperfect household decision-making. Adding a few “rational” agents with a fixed savings rate equal to the long-term optimum allows us to match business cycle timescales. Our work here supports an alternative program of research that substitutes utility maximization for behaviorally grounded decision-making.
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    A polyyne toxin produced by an antagonistic bacterium blinds and lyses a Chlamydomonad alga
    (Washington, DC : National Acad. of Sciences, 2021) Hotter, Vivien; Zopf, David; Kim, Hak Joong; Silge, Anja; Schmitt, Michael; Aiyar, Prasad; Fleck, Johanna; Matthäus, Christian; Hniopek, Julian; Yan, Qing; Loper, Joyce; Sasso, Severin; Hertweck, Christian; Popp, Jürgen; Mittag, Maria
    Algae are key contributors to global carbon fixation and form the basis of many food webs. In nature, their growth is often supported or suppressed by microorganisms. The bacterium Pseudomonas protegens Pf-5 arrests the growth of the green unicellular alga Chlamydomonas reinhardtii, deflagellates the alga by the cyclic lipopeptide orfamide A, and alters its morphology [P. Aiyar et al., Nat. Commun. 8, 1756 (2017)]. Using a combination of Raman microspectroscopy, genome mining, and mutational analysis, we discovered a polyyne toxin, protegencin, which is secreted by P. protegens, penetrates the algal cells, and causes destruction of the carotenoids of their primitive visual system, the eyespot. Together with secreted orfamide A, protegencin thus prevents the phototactic behavior of C. reinhardtii. A mutant of P. protegens deficient in protegencin production does not affect growth or eyespot carotenoids of C. reinhardtii. Protegencin acts in a direct and destructive way by lysing and killing the algal cells. The toxic effect of protegencin is also observed in an eyeless mutant and with the colony-forming Chlorophyte alga Gonium pectorale. These data reveal a two-pronged molecular strategy involving a cyclic lipopeptide and a conjugated tetrayne used by bacteria to attack select Chlamydomonad algae. In conjunction with the bloom-forming activity of several chlorophytes and the presence of the protegencin gene cluster in over 50 different Pseudomonas genomes [A. J. Mullins et al., bioRxiv [Preprint] (2021). https://www.biorxiv.org/content/10.1101/2021.03.05.433886v1 (Accessed 17 April 2021)], these data are highly relevant to ecological interactions between Chlorophyte algae and Pseudomonadales bacteria.
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    Communicating sentiment and outlook reverses inaction against collective risks
    (Washington, DC : National Acad. of Sciences, 2020) Wang, Zhen; Jusup, Marko; Guo, Hao; Shi, Lei; Geček, Sunčana; Anand, Madhur; Perc, Matjaž; Bauch, Chris T.; Kurths, Jürgen; Boccaletti, Stefano; Schellnhuber, Hans Joachim
    Collective risks permeate society, triggering social dilemmas in which working toward a common goal is impeded by selfish interests. One such dilemma is mitigating runaway climate change. To study the social aspects of climate-change mitigation, we organized an experimental game and asked volunteer groups of three different sizes to invest toward a common mitigation goal. If investments reached a preset target, volunteers would avoid all consequences and convert their remaining capital into monetary payouts. In the opposite case, however, volunteers would lose all their capital with 50% probability. The dilemma was, therefore, whether to invest one's own capital or wait for others to step in. We find that communicating sentiment and outlook helps to resolve the dilemma by a fundamental shift in investment patterns. Groups in which communication is allowed invest persistently and hardly ever give up, even when their current investment deficits are substantial. The improved investment patterns are robust to group size, although larger groups are harder to coordinate, as evidenced by their overall lower success frequencies. A clustering algorithm reveals three behavioral types and shows that communication reduces the abundance of the free-riding type. Climate-change mitigation, however, is achieved mainly by cooperator and altruist types stepping up and increasing contributions as the failure looms. Meanwhile, contributions from free riders remain flat throughout the game. This reveals that the mechanisms behind avoiding collective risks depend on an interaction between behavioral type, communication, and timing.
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    Reply to Bhowmik et al.: Democratic climate action and studying extreme climate risks are not in tension
    (Washington, DC : National Acad. of Sciences, 2022) Kemp, Luke; Xu, Chi; Depledge, Joanna; Ebi, Kristie L.; Gibbins, Goodwin; Kohler, Timothy A.; Rockström, Johan; Scheffer, Marten; Schellnhuber, Hans Joachim; Steffen, Will; Lenton, Timothy M.
    [no abstract available]
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    Reply to Ruhl and Craig: Assessing and governing extreme climate risks needs to be legitimate and democratic
    (Washington, DC : National Acad. of Sciences, 2022) Kemp, Luke; Xu, Chi; Depledge, Joanna; Ebi, Kristie L.; Gibbins, Goodwin; Kohler, Timothy A.; Rockström, Johan; Scheffer, Marten; Schellnhuber, Hans Joachim; Steffen, Will; Lenton, Timothy M.
    [No abstract available]
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    Gas plasma–oxidized sodium chloride acts via hydrogen peroxide in a model of peritoneal carcinomatosis
    (Washington, DC : National Acad. of Sciences, 2022) Miebach, Lea; Freund, Eric; Clemen, Ramona; Kersting, Stephan; Partecke, Lars-Ivo; Bekeschus, Sander
    Gas plasma technology generates reactive oxygen and nitrogen species (ROS/RNS), inducing lethal oxidative damage in tumor cells. The transfer of gas plasma–derived ROS/RNS into liquids has been proposed as an innovative anti-cancer strategy targeting peritoneal carcinomatosis (PC). However, the mechanism of action is under debate. To this end, we compared gas plasma–oxidized medical-grade sodium chloride (oxNaCl) with a concentration-matched control (cmc) of NaCl enriched with equivalent concentrations of H2O2 and NO32 in several cell lines and models of PC. Strikingly, oxNaCl and cmc performed equally well in oxidation and cytotoxic activity in tumor cells in two-dimensional cultures, three-dimensional (3D) tumor spheroids, vascularized 3D tumors grown on chicken-embryo chorioallantoic membranes, and a syngeneic PC mouse model in vivo. Given the importance of immunotherapies in oncology today, we focused on immunological consequences of the treatment. Again, to a similar extent, oxNaCl and cmc increased tumor cell immunogenicity and enhanced uptake by and maturation of peripheral blood monocyte–derived dendritic cells together with an inflammatory secretion profile. Furthermore, NanoString gene expression profiling revealed immune system processes and unfolded protein response-related pathways as being linked to the observed anti-tumor effects for both oxNaCl and cmc. In conclusion, gas plasma–generated oxNaCl and cmc showed equal therapeutic efficacy in our PC-related models. In light of the many promising anti-cancer studies of gas plasma–oxidized liquids and the convenient production of corresponding cmcs in large quantities as needed in clinics, our findings may spur research lines based on low-dose oxidants in peritoneal cancer therapy.
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    Reply to Burgess et al: Catastrophic climate risks are neglected, plausible, and safe to study
    (Washington, DC : National Acad. of Sciences, 2022) Kemp, Luke; Xu, Chi; Depledge, Joanna; Ebi, Kristie L.; Gibbins, Goodwin; Kohler, Timothy A.; Rockström, Johan; Scheffer, Marten; Schellnhuber, Hans Joachim; Steffen, Will; Lenton, Timothy M.
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    Encapsulation of hydrophobic components in dendrimersomes and decoration of their surface with proteins and nucleic acids
    (Washington, DC : National Acad. of Sciences, 2019) Torre, Paola; Xiao, Qi; Buzzacchera, Irene; Sherman, Samuel E.; Rahimi, Khosrow; Kostina, Nina Yu.; Rodriguez-Emmenegger, Cesar; Möller, Martin; Wilson, Christopher J.; Klein, Michael L.; Good, Matthew C.; Percec, Virgil
    Reconstructing the functions of living cells using nonnatural components is one of the great challenges of natural sciences. Compartmentalization, encapsulation, and surface decoration of globular assemblies, known as vesicles, represent key early steps in the reconstitution of synthetic cells. Here we report that vesicles self-assembled from amphiphilic Janus dendrimers, called dendrimersomes, encapsulate high concentrations of hydrophobic components and do so more efficiently than commercially available stealth liposomes assembled from phospholipid components. Multilayer onion-like dendrimersomes demonstrate a particularly high capacity for loading low-molecular weight compounds and even folded proteins. Coassembly of amphiphilic Janus dendrimers with metal-chelating ligands conjugated to amphiphilic Janus dendrimers generates dendrimersomes that selectively display folded proteins on their periphery in an oriented manner. A modular strategy for tethering nucleic acids to the surface of dendrimersomes is also demonstrated. These findings augment the functional capabilities of dendrimersomes to serve as versatile biological membrane mimics.