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- ItemReply 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]
- ItemReply 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.
- ItemGas 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, SanderGas 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.
- ItemStewardship of global collective behavior(Washington, DC : National Acad. of Sciences, 2021) Bak-Coleman, Joseph B.; Alfano, Mark; Barfuss, Wolfram; Bergstrom, Carl T.; Centeno, Miguel A.; Couzin, Iain D.; Donges, Jonathan F.; Galesic, Mirta; Gersick, Andrew S.; Jacquet, Jennifer; Kao, Albert B.; Moran, Rachel E.; Romanczuk, Pawel; Rubenstein, Daniel I.; Tombak, Kaia J.; Van Bavel, Jay J.; Weber, Elke U.Collective behavior provides a framework for understanding how the actions and properties of groups emerge from the way individuals generate and share information. In humans, information flows were initially shaped by natural selection yet are increasingly structured by emerging communication technologies. Our larger, more complex social networks now transfer high-fidelity information over vast distances at low cost. The digital age and the rise of social media have accelerated changes to our social systems, with poorly understood functional consequences. This gap in our knowledge represents a principal challenge to scientific progress, democracy, and actions to address global crises. We argue that the study of collective behavior must rise to a “crisis discipline” just as medicine, conservation, and climate science have, with a focus on providing actionable insight to policymakers and regulators for the stewardship of social systems.
- ItemCommunicating sentiment and outlook reverses inaction against collective risks(Washington, DC : National Acad. of Sciences, 2020) Wang, Zhen; Jusup, Marko; Guo, Hao; Shi, Lei; GeÄŤek, SunÄŤana; Anand, Madhur; Perc, MatjaĹľ; Bauch, Chris T.; Kurths, JĂĽrgen; Boccaletti, Stefano; Schellnhuber, Hans JoachimCollective 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.
- ItemDesign–functionality relationships for adhesion/growth-regulatory galectins(Washington, DC : National Acad. of Sciences, 2019) Ludwig, Anna-Kristin; Michalak, Malwina; Xiao, Qi; Gilles, Ulrich; Medrano, Francisco J.; Ma, Hanyue; FitzGerald, Forrest G.; Hasley, William D.; Melendez-Davila, Adriel; Liu, Matthew; Rahimi, Khosrow; Kostina, Nina Yu; Rodriguez-Emmenegger, Cesar; Möller, Martin; Lindner, Ingo; Kaltner, Herbert; Cudic, Mare; Reusch, Dietmar; Kopitz, Jürgen; Romero, Antonio; Oscarson, Stefan; Klein, Michael L.; Gabius, Hans-Joachim; Percec, VirgilGlycan-lectin recognition is assumed to elicit its broad range of (patho)physiological functions via a combination of specific contact formation with generation of complexes of distinct signal-triggering topology on biomembranes. Faced with the challenge to understand why evolution has led to three particular modes of modular architecture for adhesion/growth-regulatory galectins in vertebrates, here we introduce protein engineering to enable design switches. The impact of changes is measured in assays on cell growth and on bridging fully synthetic nanovesicles (glycodendrimersomes) with a chemically programmable surface. Using the example of homodimeric galectin-1 and monomeric galectin-3, the mutual design conversion caused qualitative differences, i.e., from bridging effector to antagonist/from antagonist to growth inhibitor and vice versa. In addition to attaining proof-of-principle evidence for the hypothesis that chimera-type galectin-3 design makes functional antagonism possible, we underscore the value of versatile surface programming with a derivative of the pan-galectin ligand lactose. Aggregation assays with N,N′-diacetyllactosamine establishing a parasite-like surface signature revealed marked selectivity among the family of galectins and bridging potency of homodimers. These findings provide fundamental insights into design-functionality relationships of galectins. Moreover, our strategy generates the tools to identify biofunctional lattice formation on biomembranes and galectin-reagents with therapeutic potential.
- ItemWe need biosphere stewardship that protects carbon sinks and builds resilience(Washington, DC : National Acad. of Sciences, 2021) Rockström, Johan; Beringer, Tim; Hole, David; Griscom, Bronson; Mascia, Michael B.; Folke, Carl; Creutzig, Felix[no abstract available]
- ItemReply 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]
- ItemA regional nuclear conflict would compromise global food security(Washington, DC : National Acad. of Sciences, 2020) Jägermeyr, Jonas; Robock, Alan; Elliott, Joshua; Müller, Christoph; Xia, Lili; Khabarov, Nikolay; Folberth, Christian; Schmid, Erwin; Liu, Wenfeng; Zabel, Florian; Rabin, Sam S.; Puma, Michael J.; Heslin, Alison; Franke, James; Foster, Ian; Asseng, Senthold; Bardeen, Charles G.; Toon, Owen B.; Rosenzweig, CynthiaA limited nuclear war between India and Pakistan could ignite fires large enough to emit more than 5 Tg of soot into the stratosphere. Climate model simulations have shown severe resulting climate perturbations with declines in global mean temperature by 1.8 °C and precipitation by 8%, for at least 5 y. Here we evaluate impacts for the global food system. Six harmonized state-of-the-art crop models show that global caloric production from maize, wheat, rice, and soybean falls by 13 (±1)%, 11 (±8)%, 3 (±5)%, and 17 (±2)% over 5 y. Total single-year losses of 12 (±4)% quadruple the largest observed historical anomaly and exceed impacts caused by historic droughts and volcanic eruptions. Colder temperatures drive losses more than changes in precipitation and solar radiation, leading to strongest impacts in temperate regions poleward of 30°N, including the United States, Europe, and China for 10 to 15 y. Integrated food trade network analyses show that domestic reserves and global trade can largely buffer the production anomaly in the first year. Persistent multiyear losses, however, would constrain domestic food availability and propagate to the Global South, especially to food-insecure countries. By year 5, maize and wheat availability would decrease by 13% globally and by more than 20% in 71 countries with a cumulative population of 1.3 billion people. In view of increasing instability in South Asia, this study shows that a regional conflict using <1% of the worldwide nuclear arsenal could have adverse consequences for global food security unmatched in modern history.
- ItemPhylodynamic signatures in the emergence of community-associated MRSA(Washington, DC : National Acad. of Sciences, 2022) Steinig, Eike; Aglua, Izzard; Duchene, Sebastian; Meehan, Michael T.; Yoannes, Mition; Firth, Cadhla; Jaworski, Jan; Drekore, Jimmy; Urakoko, Bohu; Poka, Harry; Wurr, Clive; Ebos, Eri; Nangen, David; MĂĽller, Elke; Mulvey, Peter; Jackson, Charlene; Blomfeldt, Anita; Aamot, Hege Vangstein; Laman, Moses; Manning, Laurens; Earls, Megan; Coleman, David C.; Greenhill, Andrew; Ford, Rebecca; Stegger, Marc; Syed, Muhammad Ali; Jamil, Bushra; Monecke, Stefan; Ehricht, Ralf; Smith, Simon; Pomat, William; Horwood, Paul; Tong, Steven Y. C.; McBryde, EmmaCommunity-associated, methicillin-resistant Staphylococcus aureus (MRSA) lineages have emerged in many geographically distinct regions around the world during the past 30 y. Here, we apply consistent phylodynamic methods across multiple community-associated MRSA lineages to describe and contrast their patterns of emergence and dissemination. We generated whole-genome sequencing data for the Australian sequence type (ST) ST93-MRSA-IV from remote communities in Far North Queensland and Papua New Guinea, and the Bengal Bay ST772-MRSA-V clone from metropolitan communities in Pakistan. Increases in the effective reproduction number (Re) and sustained transmission (Re > 1) coincided with spread of progenitor methicillin-susceptible S. aureus (MSSA) in remote northern Australian populations, dissemination of the ST93-MRSA-IV genotype into population centers on the Australian East Coast, and subsequent importation into the highlands of Papua New Guinea and Far North Queensland. Applying the same phylodynamic methods to existing lineage datasets, we identified common signatures of epidemic growth in the emergence and epidemiological trajectory of community-associated S. aureus lineages from America, Asia, Australasia, and Europe. Surges in Re were observed at the divergence of antibiotic-resistant strains, coinciding with their establishment in regional population centers. Epidemic growth was also observed among drug-resistant MSSA clades in Africa and northern Australia. Our data suggest that the emergence of community-associated MRSA in the late 20th century was driven by a combination of antibiotic-resistant genotypes and host epidemiology, leading to abrupt changes in lineage-wide transmission dynamics and sustained transmission in regional population centers.