@article{8317, abstract = {When can a polyomino piece of paper be folded into a unit cube? Prior work studied tree-like polyominoes, but polyominoes with holes remain an intriguing open problem. We present sufficient conditions for a polyomino with one or several holes to fold into a cube, and conditions under which cube folding is impossible. In particular, we show that all but five special “basic” holes guarantee foldability.}, author = {Aichholzer, Oswin and Akitaya, Hugo A. and Cheung, Kenneth C. and Demaine, Erik D. and Demaine, Martin L. and Fekete, Sándor P. and Kleist, Linda and Kostitsyna, Irina and Löffler, Maarten and Masárová, Zuzana and Mundilova, Klara and Schmidt, Christiane}, issn = {09257721}, journal = {Computational Geometry: Theory and Applications}, publisher = {Elsevier}, title = {{Folding polyominoes with holes into a cube}}, doi = {10.1016/j.comgeo.2020.101700}, volume = {93}, year = {2021}, } @article{8373, abstract = {It is well known that special Kubo-Ando operator means admit divergence center interpretations, moreover, they are also mean squared error estimators for certain metrics on positive definite operators. In this paper we give a divergence center interpretation for every symmetric Kubo-Ando mean. This characterization of the symmetric means naturally leads to a definition of weighted and multivariate versions of a large class of symmetric Kubo-Ando means. We study elementary properties of these weighted multivariate means, and note in particular that in the special case of the geometric mean we recover the weighted A#H-mean introduced by Kim, Lawson, and Lim.}, author = {Pitrik, József and Virosztek, Daniel}, issn = {0024-3795}, journal = {Linear Algebra and its Applications}, keywords = {Kubo-Ando mean, weighted multivariate mean, barycenter}, pages = {203--217}, publisher = {Elsevier}, title = {{A divergence center interpretation of general symmetric Kubo-Ando means, and related weighted multivariate operator means}}, doi = {10.1016/j.laa.2020.09.007}, volume = {609}, year = {2021}, } @article{8582, abstract = {Cell and tissue polarization is fundamental for plant growth and morphogenesis. The polar, cellular localization of Arabidopsis PIN‐FORMED (PIN) proteins is crucial for their function in directional auxin transport. The clustering of PIN polar cargoes within the plasma membrane has been proposed to be important for the maintenance of their polar distribution. However, the more detailed features of PIN clusters and the cellular requirements of cargo clustering remain unclear. Here, we characterized PIN clusters in detail by means of multiple advanced microscopy and quantification methods, such as 3D quantitative imaging or freeze‐fracture replica labeling. The size and aggregation types of PIN clusters were determined by electron microscopy at the nanometer level at different polar domains and at different developmental stages, revealing a strong preference for clustering at the polar domains. Pharmacological and genetic studies revealed that PIN clusters depend on phosphoinositol pathways, cytoskeletal structures and specific cell‐wall components as well as connections between the cell wall and the plasma membrane. This study identifies the role of different cellular processes and structures in polar cargo clustering and provides initial mechanistic insight into the maintenance of polarity in plants and other systems.}, author = {Li, Hongjiang and von Wangenheim, Daniel and Zhang, Xixi and Tan, Shutang and Darwish-Miranda, Nasser and Naramoto, Satoshi and Wabnik, Krzysztof T and de Rycke, Riet and Kaufmann, Walter and Gütl, Daniel J and Tejos, Ricardo and Grones, Peter and Ke, Meiyu and Chen, Xu and Dettmer, Jan and Friml, Jiří}, issn = {14698137}, journal = {New Phytologist}, number = {1}, pages = {351--369}, publisher = {Wiley}, title = {{Cellular requirements for PIN polar cargo clustering in Arabidopsis thaliana}}, doi = {10.1111/nph.16887}, volume = {229}, year = {2021}, } @article{8608, abstract = {To adapt to the diverse array of biotic and abiotic cues, plants have evolved sophisticated mechanisms to sense changes in environmental conditions and modulate their growth. Growth-promoting hormones and defence signalling fine tune plant development antagonistically. During host-pathogen interactions, this defence-growth trade-off is mediated by the counteractive effects of the defence hormone salicylic acid (SA) and the growth hormone auxin. Here we revealed an underlying mechanism of SA regulating auxin signalling by constraining the plasma membrane dynamics of PIN2 auxin efflux transporter in Arabidopsis thaliana roots. The lateral diffusion of PIN2 proteins is constrained by SA signalling, during which PIN2 proteins are condensed into hyperclusters depending on REM1.2-mediated nanodomain compartmentalisation. Furthermore, membrane nanodomain compartmentalisation by SA or Remorin (REM) assembly significantly suppressed clathrin-mediated endocytosis. Consequently, SA-induced heterogeneous surface condensation disrupted asymmetric auxin distribution and the resultant gravitropic response. Our results demonstrated a defence-growth trade-off mechanism by which SA signalling crosstalked with auxin transport by concentrating membrane-resident PIN2 into heterogeneous compartments.}, author = {Ke, M and Ma, Z and Wang, D and Sun, Y and Wen, C and Huang, D and Chen, Z and Yang, L and Tan, Shutang and Li, R and Friml, Jiří and Miao, Y and Chen, X}, issn = {0028-646x}, journal = {New Phytologist}, number = {2}, pages = {963--978}, publisher = {Wiley}, title = {{Salicylic acid regulates PIN2 auxin transporter hyper-clustering and root gravitropic growth via Remorin-dependent lipid nanodomain organization in Arabidopsis thaliana}}, doi = {10.1111/nph.16915}, volume = {229}, year = {2021}, } @article{8742, abstract = {We develop a version of Ekedahl’s geometric sieve for integral quadratic forms of rank at least five. As one ranges over the zeros of such quadratic forms, we use the sieve to compute the density of coprime values of polynomials, and furthermore, to address a question about local solubility in families of varieties parameterised by the zeros.}, author = {Browning, Timothy D and Heath-Brown, Roger}, issn = {14355337}, journal = {Forum Mathematicum}, number = {1}, pages = {147--165}, publisher = {De Gruyter}, title = {{The geometric sieve for quadrics}}, doi = {10.1515/forum-2020-0074}, volume = {33}, year = {2021}, } @article{8757, abstract = {Traditional scientific conferences and seminar events have been hugely disrupted by the COVID-19 pandemic, paving the way for virtual forms of scientific communication to take hold and be put to the test.}, author = {Bozelos, Panagiotis and Vogels, Tim P}, issn = {14710048}, journal = {Nature Reviews Neuroscience}, number = {1}, pages = {1--2}, publisher = {Springer Nature}, title = {{Talking science, online}}, doi = {10.1038/s41583-020-00408-6}, volume = {22}, year = {2021}, } @article{8773, abstract = {Let g be a complex semisimple Lie algebra. We give a classification of contravariant forms on the nondegenerate Whittaker g-modules Y(χ,η) introduced by Kostant. We prove that the set of all contravariant forms on Y(χ,η) forms a vector space whose dimension is given by the cardinality of the Weyl group of g. We also describe a procedure for parabolically inducing contravariant forms. As a corollary, we deduce the existence of the Shapovalov form on a Verma module, and provide a formula for the dimension of the space of contravariant forms on the degenerate Whittaker modules M(χ,η) introduced by McDowell.}, author = {Brown, Adam and Romanov, Anna}, issn = {1088-6826}, journal = {Proceedings of the American Mathematical Society}, keywords = {Applied Mathematics, General Mathematics}, number = {1}, pages = {37--52}, publisher = {American Mathematical Society}, title = {{Contravariant forms on Whittaker modules}}, doi = {10.1090/proc/15205}, volume = {149}, year = {2021}, } @article{8793, abstract = {We study optimal election sequences for repeatedly selecting a (very) small group of leaders among a set of participants (players) with publicly known unique ids. In every time slot, every player has to select exactly one player that it considers to be the current leader, oblivious to the selection of the other players, but with the overarching goal of maximizing a given parameterized global (“social”) payoff function in the limit. We consider a quite generic model, where the local payoff achieved by a given player depends, weighted by some arbitrary but fixed real parameter, on the number of different leaders chosen in a round, the number of players that choose the given player as the leader, and whether the chosen leader has changed w.r.t. the previous round or not. The social payoff can be the maximum, average or minimum local payoff of the players. Possible applications include quite diverse examples such as rotating coordinator-based distributed algorithms and long-haul formation flying of social birds. Depending on the weights and the particular social payoff, optimal sequences can be very different, from simple round-robin where all players chose the same leader alternatingly every time slot to very exotic patterns, where a small group of leaders (at most 2) is elected in every time slot. Moreover, we study the question if and when a single player would not benefit w.r.t. its local payoff when deviating from the given optimal sequence, i.e., when our optimal sequences are Nash equilibria in the restricted strategy space of oblivious strategies. As this is the case for many parameterizations of our model, our results reveal that no punishment is needed to make it rational for the players to optimize the social payoff.}, author = {Zeiner, Martin and Schmid, Ulrich and Chatterjee, Krishnendu}, issn = {0166218X}, journal = {Discrete Applied Mathematics}, number = {1}, pages = {392--415}, publisher = {Elsevier}, title = {{Optimal strategies for selecting coordinators}}, doi = {10.1016/j.dam.2020.10.022}, volume = {289}, year = {2021}, } @article{8816, abstract = {Area-dependent quantum field theory is a modification of two-dimensional topological quantum field theory, where one equips each connected component of a bordism with a positive real number—interpreted as area—which behaves additively under glueing. As opposed to topological theories, in area-dependent theories the state spaces can be infinite-dimensional. We introduce the notion of regularised Frobenius algebras in Hilbert spaces and show that area-dependent theories are in one-to-one correspondence to commutative regularised Frobenius algebras. We also provide a state sum construction for area-dependent theories. Our main example is two-dimensional Yang–Mills theory with compact gauge group, which we treat in detail.}, author = {Runkel, Ingo and Szegedy, Lorant}, issn = {14320916}, journal = {Communications in Mathematical Physics}, number = {1}, pages = {83–117}, publisher = {Springer Nature}, title = {{Area-dependent quantum field theory}}, doi = {10.1007/s00220-020-03902-1}, volume = {381}, year = {2021}, } @article{8818, abstract = {The hippocampus has a major role in encoding and consolidating long-term memories, and undergoes plastic changes during sleep1. These changes require precise homeostatic control by subcortical neuromodulatory structures2. The underlying mechanisms of this phenomenon, however, remain unknown. Here, using multi-structure recordings in macaque monkeys, we show that the brainstem transiently modulates hippocampal network events through phasic pontine waves known as pontogeniculooccipital waves (PGO waves). Two physiologically distinct types of PGO wave appear to occur sequentially, selectively influencing high-frequency ripples and low-frequency theta events, respectively. The two types of PGO wave are associated with opposite hippocampal spike-field coupling, prompting periods of high neural synchrony of neural populations during periods of ripple and theta instances. The coupling between PGO waves and ripples, classically associated with distinct sleep stages, supports the notion that a global coordination mechanism of hippocampal sleep dynamics by cholinergic pontine transients may promote systems and synaptic memory consolidation as well as synaptic homeostasis.}, author = {Ramirez Villegas, Juan F and Besserve, Michel and Murayama, Yusuke and Evrard, Henry C. and Oeltermann, Axel and Logothetis, Nikos K.}, issn = {14764687}, journal = {Nature}, number = {7840}, pages = {96--102}, publisher = {Springer Nature}, title = {{Coupling of hippocampal theta and ripples with pontogeniculooccipital waves}}, doi = {10.1038/s41586-020-2914-4}, volume = {589}, year = {2021}, } @article{8824, abstract = {Plants are able to orient their growth according to gravity, which ultimately controls both shoot and root architecture.1 Gravitropism is a dynamic process whereby gravistimulation induces the asymmetric distribution of the plant hormone auxin, leading to asymmetric growth, organ bending, and subsequent reset of auxin distribution back to the original pre-gravistimulation situation.1, 2, 3 Differential auxin accumulation during the gravitropic response depends on the activity of polarly localized PIN-FORMED (PIN) auxin-efflux carriers.1, 2, 3, 4 In particular, the timing of this dynamic response is regulated by PIN2,5,6 but the underlying molecular mechanisms are poorly understood. Here, we show that MEMBRANE ASSOCIATED KINASE REGULATOR2 (MAKR2) controls the pace of the root gravitropic response. We found that MAKR2 is required for the PIN2 asymmetry during gravitropism by acting as a negative regulator of the cell-surface signaling mediated by the receptor-like kinase TRANSMEMBRANE KINASE1 (TMK1).2,7, 8, 9, 10 Furthermore, we show that the MAKR2 inhibitory effect on TMK1 signaling is antagonized by auxin itself, which triggers rapid MAKR2 membrane dissociation in a TMK1-dependent manner. Our findings suggest that the timing of the root gravitropic response is orchestrated by the reversible inhibition of the TMK1 signaling pathway at the cell surface.}, author = {Marquès-Bueno, MM and Armengot, L and Noack, LC and Bareille, J and Rodriguez Solovey, Lesia and Platre, MP and Bayle, V and Liu, M and Opdenacker, D and Vanneste, S and Möller, BK and Nimchuk, ZL and Beeckman, T and Caño-Delgado, AI and Friml, Jiří and Jaillais, Y}, issn = {0960-9822}, journal = {Current Biology}, number = {1}, publisher = {Elsevier}, title = {{Auxin-regulated reversible inhibition of TMK1 signaling by MAKR2 modulates the dynamics of root gravitropism}}, doi = {10.1016/j.cub.2020.10.011}, volume = {31}, year = {2021}, } @article{7551, abstract = {Novelty facilitates formation of memories. The detection of novelty and storage of contextual memories are both mediated by the hippocampus, yet the mechanisms that link these two functions remain to be defined. Dentate granule cells (GCs) of the dorsal hippocampus fire upon novelty exposure forming engrams of contextual memory. However, their key excitatory inputs from the entorhinal cortex are not responsive to novelty and are insufficient to make dorsal GCs fire reliably. Here we uncover a powerful glutamatergic pathway to dorsal GCs from ventral hippocampal mossy cells (MCs) that relays novelty, and is necessary and sufficient for driving dorsal GCs activation. Furthermore, manipulation of ventral MCs activity bidirectionally regulates novelty-induced contextual memory acquisition. Our results show that ventral MCs activity controls memory formation through an intra-hippocampal interaction mechanism gated by novelty.}, author = {Fredes Tolorza, Felipe A and Silva Sifuentes, Maria A and Koppensteiner, Peter and Kobayashi, Kenta and Jösch, Maximilian A and Shigemoto, Ryuichi}, journal = {Current Biology}, number = {1}, pages = {P25--38.E5}, publisher = {Elsevier}, title = {{Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation}}, doi = {10.1016/j.cub.2020.09.074}, volume = {31}, year = {2021}, } @article{7685, abstract = {We consider a gas of interacting bosons trapped in a box of side length one in the Gross–Pitaevskii limit. We review the proof of the validity of Bogoliubov’s prediction for the ground state energy and the low-energy excitation spectrum. This note is based on joint work with C. Brennecke, S. Cenatiempo and B. Schlein.}, author = {Boccato, Chiara}, issn = {0129-055X}, journal = {Reviews in Mathematical Physics}, number = {1}, publisher = {World Scientific}, title = {{The excitation spectrum of the Bose gas in the Gross-Pitaevskii regime}}, doi = {10.1142/S0129055X20600065}, volume = {33}, year = {2021}, } @article{7900, abstract = {Hartree–Fock theory has been justified as a mean-field approximation for fermionic systems. However, it suffers from some defects in predicting physical properties, making necessary a theory of quantum correlations. Recently, bosonization of many-body correlations has been rigorously justified as an upper bound on the correlation energy at high density with weak interactions. We review the bosonic approximation, deriving an effective Hamiltonian. We then show that for systems with Coulomb interaction this effective theory predicts collective excitations (plasmons) in accordance with the random phase approximation of Bohm and Pines, and with experimental observation.}, author = {Benedikter, Niels P}, issn = {0129-055X}, journal = {Reviews in Mathematical Physics}, number = {1}, publisher = {World Scientific}, title = {{Bosonic collective excitations in Fermi gases}}, doi = {10.1142/s0129055x20600090}, volume = {33}, year = {2021}, } @article{8927, abstract = {The recent outbreak of coronavirus disease 2019 (COVID‐19), caused by the Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) has resulted in a world‐wide pandemic. Disseminated lung injury with the development of acute respiratory distress syndrome (ARDS) is the main cause of mortality in COVID‐19. Although liver failure does not seem to occur in the absence of pre‐existing liver disease, hepatic involvement in COVID‐19 may correlate with overall disease severity and serve as a prognostic factor for the development of ARDS. The spectrum of liver injury in COVID‐19 may range from direct infection by SARS‐CoV‐2, indirect involvement by systemic inflammation, hypoxic changes, iatrogenic causes such as drugs and ventilation to exacerbation of underlying liver disease. This concise review discusses the potential pathophysiological mechanisms for SARS‐CoV‐2 hepatic tropism as well as acute and possibly long‐term liver injury in COVID‐19.}, author = {Nardo, Alexander D. and Schneeweiss-Gleixner, Mathias and Bakail, May M and Dixon, Emmanuel D. and Lax, Sigurd F. and Trauner, Michael}, issn = {14783231}, journal = {Liver International}, number = {1}, pages = {20--32}, publisher = {Wiley}, title = {{Pathophysiological mechanisms of liver injury in COVID-19}}, doi = {10.1111/liv.14730}, volume = {41}, year = {2021}, } @article{8931, abstract = {Auxin is a major plant growth regulator, but current models on auxin perception and signaling cannot explain the whole plethora of auxin effects, in particular those associated with rapid responses. A possible candidate for a component of additional auxin perception mechanisms is the AUXIN BINDING PROTEIN 1 (ABP1), whose function in planta remains unclear. Here we combined expression analysis with gain- and loss-of-function approaches to analyze the role of ABP1 in plant development. ABP1 shows a broad expression largely overlapping with, but not regulated by, transcriptional auxin response activity. Furthermore, ABP1 activity is not essential for the transcriptional auxin signaling. Genetic in planta analysis revealed that abp1 loss-of-function mutants show largely normal development with minor defects in bolting. On the other hand, ABP1 gain-of-function alleles show a broad range of growth and developmental defects, including root and hypocotyl growth and bending, lateral root and leaf development, bolting, as well as response to heat stress. At the cellular level, ABP1 gain-of-function leads to impaired auxin effect on PIN polar distribution and affects BFA-sensitive PIN intracellular aggregation. The gain-of-function analysis suggests a broad, but still mechanistically unclear involvement of ABP1 in plant development, possibly masked in abp1 loss-of-function mutants by a functional redundancy.}, author = {Gelová, Zuzana and Gallei, Michelle C and Pernisová, Markéta and Brunoud, Géraldine and Zhang, Xixi and Glanc, Matous and Li, Lanxin and Michalko, Jaroslav and Pavlovicova, Zlata and Verstraeten, Inge and Han, Huibin and Hajny, Jakub and Hauschild, Robert and Čovanová, Milada and Zwiewka, Marta and Hörmayer, Lukas and Fendrych, Matyas and Xu, Tongda and Vernoux, Teva and Friml, Jiří}, issn = {0168-9452}, journal = {Plant Science}, keywords = {Agronomy and Crop Science, Plant Science, Genetics, General Medicine}, publisher = {Elsevier}, title = {{Developmental roles of auxin binding protein 1 in Arabidopsis thaliana}}, doi = {10.1016/j.plantsci.2020.110750}, volume = {303}, year = {2021}, } @article{8988, abstract = {The differentiation of cells depends on a precise control of their internal organization, which is the result of a complex dynamic interplay between the cytoskeleton, molecular motors, signaling molecules, and membranes. For example, in the developing neuron, the protein ADAP1 (ADP-ribosylation factor GTPase-activating protein [ArfGAP] with dual pleckstrin homology [PH] domains 1) has been suggested to control dendrite branching by regulating the small GTPase ARF6. Together with the motor protein KIF13B, ADAP1 is also thought to mediate delivery of the second messenger phosphatidylinositol (3,4,5)-trisphosphate (PIP3) to the axon tip, thus contributing to PIP3 polarity. However, what defines the function of ADAP1 and how its different roles are coordinated are still not clear. Here, we studied ADAP1’s functions using in vitro reconstitutions. We found that KIF13B transports ADAP1 along microtubules, but that PIP3 as well as PI(3,4)P2 act as stop signals for this transport instead of being transported. We also demonstrate that these phosphoinositides activate ADAP1’s enzymatic activity to catalyze GTP hydrolysis by ARF6. Together, our results support a model for the cellular function of ADAP1, where KIF13B transports ADAP1 until it encounters high PIP3/PI(3,4)P2 concentrations in the plasma membrane. Here, ADAP1 disassociates from the motor to inactivate ARF6, promoting dendrite branching.}, author = {Düllberg, Christian F and Auer, Albert and Canigova, Nikola and Loibl, Katrin and Loose, Martin}, issn = {10916490}, journal = {PNAS}, number = {1}, publisher = {National Academy of Sciences}, title = {{In vitro reconstitution reveals phosphoinositides as cargo-release factors and activators of the ARF6 GAP ADAP1}}, doi = {10.1073/pnas.2010054118}, volume = {118}, year = {2021}, } @article{8992, abstract = {The phytohormone auxin plays a central role in shaping plant growth and development. With decades of genetic and biochemical studies, numerous core molecular components and their networks, underlying auxin biosynthesis, transport, and signaling, have been identified. Notably, protein phosphorylation, catalyzed by kinases and oppositely hydrolyzed by phosphatases, has been emerging to be a crucial type of post-translational modification, regulating physiological and developmental auxin output at all levels. In this review, we comprehensively discuss earlier and recent advances in our understanding of genetics, biochemistry, and cell biology of the kinases and phosphatases participating in auxin action. We provide insights into the mechanisms by which reversible protein phosphorylation defines developmental auxin responses, discuss current challenges, and provide our perspectives on future directions involving the integration of the control of protein phosphorylation into the molecular auxin network.}, author = {Tan, Shutang and Luschnig, Christian and Friml, Jiří}, issn = {17529867}, journal = {Molecular Plant}, number = {1}, pages = {151--165}, publisher = {Elsevier}, title = {{Pho-view of auxin: Reversible protein phosphorylation in auxin biosynthesis, transport and signaling}}, doi = {10.1016/j.molp.2020.11.004}, volume = {14}, year = {2021}, } @article{8993, abstract = {N-1-naphthylphthalamic acid (NPA) is a key inhibitor of directional (polar) transport of the hormone auxin in plants. For decades, it has been a pivotal tool in elucidating the unique polar auxin transport-based processes underlying plant growth and development. Its exact mode of action has long been sought after and is still being debated, with prevailing mechanistic schemes describing only indirect connections between NPA and the main transporters responsible for directional transport, namely PIN auxin exporters. Here we present data supporting a model in which NPA associates with PINs in a more direct manner than hitherto postulated. We show that NPA inhibits PIN activity in a heterologous oocyte system and that expression of NPA-sensitive PINs in plant, yeast, and oocyte membranes leads to specific saturable NPA binding. We thus propose that PINs are a bona fide NPA target. This offers a straightforward molecular basis for NPA inhibition of PIN-dependent auxin transport and a logical parsimonious explanation for the known physiological effects of NPA on plant growth, as well as an alternative hypothesis to interpret past and future results. We also introduce PIN dimerization and describe an effect of NPA on this, suggesting that NPA binding could be exploited to gain insights into structural aspects of PINs related to their transport mechanism.}, author = {Abas, Lindy and Kolb, Martina and Stadlmann, Johannes and Janacek, Dorina P. and Lukic, Kristina and Schwechheimer, Claus and Sazanov, Leonid A and Mach, Lukas and Friml, Jiří and Hammes, Ulrich Z.}, issn = {10916490}, journal = {PNAS}, number = {1}, publisher = {National Academy of Sciences}, title = {{Naphthylphthalamic acid associates with and inhibits PIN auxin transporters}}, doi = {10.1073/pnas.2020857118}, volume = {118}, year = {2021}, } @article{8997, abstract = {Phenomenological relations such as Ohm’s or Fourier’s law have a venerable history in physics but are still scarce in biology. This situation restrains predictive theory. Here, we build on bacterial “growth laws,” which capture physiological feedback between translation and cell growth, to construct a minimal biophysical model for the combined action of ribosome-targeting antibiotics. Our model predicts drug interactions like antagonism or synergy solely from responses to individual drugs. We provide analytical results for limiting cases, which agree well with numerical results. We systematically refine the model by including direct physical interactions of different antibiotics on the ribosome. In a limiting case, our model provides a mechanistic underpinning for recent predictions of higher-order interactions that were derived using entropy maximization. We further refine the model to include the effects of antibiotics that mimic starvation and the presence of resistance genes. We describe the impact of a starvation-mimicking antibiotic on drug interactions analytically and verify it experimentally. Our extended model suggests a change in the type of drug interaction that depends on the strength of resistance, which challenges established rescaling paradigms. We experimentally show that the presence of unregulated resistance genes can lead to altered drug interaction, which agrees with the prediction of the model. While minimal, the model is readily adaptable and opens the door to predicting interactions of second and higher-order in a broad range of biological systems.}, author = {Kavcic, Bor and Tkačik, Gašper and Bollenbach, Tobias}, issn = {1553-7358}, journal = {PLOS Computational Biology}, keywords = {Modelling and Simulation, Genetics, Molecular Biology, Antibiotics, Drug interactions}, publisher = {Public Library of Science}, title = {{Minimal biophysical model of combined antibiotic action}}, doi = {10.1371/journal.pcbi.1008529}, volume = {17}, year = {2021}, }