@article{8730, abstract = {P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) restrict at the blood–brain barrier (BBB) the brain distribution of the majority of currently known molecularly targeted anticancer drugs. To improve brain delivery of dual ABCB1/ABCG2 substrates, both ABCB1 and ABCG2 need to be inhibited simultaneously at the BBB. We examined the feasibility of simultaneous ABCB1/ABCG2 inhibition with i.v. co-infusion of erlotinib and tariquidar by studying brain distribution of the model ABCB1/ABCG2 substrate [11C]erlotinib in mice and rhesus macaques with PET. Tolerability of the erlotinib/tariquidar combination was assessed in human embryonic stem cell-derived cerebral organoids. In mice and macaques, baseline brain distribution of [11C]erlotinib was low (brain distribution volume, VT,brain < 0.3 mL/cm3). Co-infusion of erlotinib and tariquidar increased VT,brain in mice by 3.0-fold and in macaques by 3.4- to 5.0-fold, while infusion of erlotinib alone or tariquidar alone led to less pronounced VT,brain increases in both species. Treatment of cerebral organoids with erlotinib/tariquidar led to an induction of Caspase-3-dependent apoptosis. Co-infusion of erlotinib/tariquidar may potentially allow for complete ABCB1/ABCG2 inhibition at the BBB, while simultaneously achieving brain-targeted EGFR inhibition. Our protocol may be applicable to enhance brain delivery of molecularly targeted anticancer drugs for a more effective treatment of brain tumors.}, author = {Tournier, N and Goutal, S and Mairinger, S and Lozano, IH and Filip, T and Sauberer, M and Caillé, F and Breuil, L and Stanek, J and Freeman, AF and Novarino, Gaia and Truillet, C and Wanek, T and Langer, O}, issn = {1559-7016}, journal = {Journal of Cerebral Blood Flow and Metabolism}, number = {7}, pages = {1634--1646}, publisher = {SAGE Publications}, title = {{Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib}}, doi = {10.1177/0271678X20965500}, volume = {41}, 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 = {1435-5337}, 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{8743, abstract = {Montane cloud forests are areas of high endemism, and are one of the more vulnerable terrestrial ecosystems to climate change. Thus, understanding how they both contribute to the generation of biodiversity, and will respond to ongoing climate change, are important and related challenges. The widely accepted model for montane cloud forest dynamics involves upslope forcing of their range limits with global climate warming. However, limited climate data provides some support for an alternative model, where range limits are forced downslope with climate warming. Testing between these two models is challenging, due to the inherent limitations of climate and pollen records. We overcome this with an alternative source of historical information, testing between competing model predictions using genomic data and demographic analyses for a species of beetle tightly associated to an oceanic island cloud forest. Results unequivocally support the alternative model: populations that were isolated at higher elevation peaks during the Last Glacial Maximum are now in contact and hybridizing at lower elevations. Our results suggest that genomic data are a rich source of information to further understand how montane cloud forest biodiversity originates, and how it is likely to be impacted by ongoing climate change.}, author = {Salces-Castellano, Antonia and Stankowski, Sean and Arribas, Paula and Patino, Jairo and Karger, Dirk N. and Butlin, Roger and Emerson, Brent C.}, issn = {1558-5646}, journal = {Evolution}, number = {2}, pages = {231--244}, publisher = {Wiley}, title = {{Long-term cloud forest response to climate warming revealed by insect speciation history}}, doi = {10.1111/evo.14111}, volume = {75}, 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 = {1471-0048}, 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{8792, abstract = {This paper is concerned with a non-isothermal Cahn-Hilliard model based on a microforce balance. The model was derived by A. Miranville and G. Schimperna starting from the two fundamental laws of Thermodynamics, following M. Gurtin's two-scale approach. The main working assumptions are made on the behaviour of the heat flux as the absolute temperature tends to zero and to infinity. A suitable Ginzburg-Landau free energy is considered. Global-in-time existence for the initial-boundary value problem associated to the entropy formulation and, in a subcase, also to the weak formulation of the model is proved by deriving suitable a priori estimates and by showing weak sequential stability of families of approximating solutions. At last, some highlights are given regarding a possible approximation scheme compatible with the a-priori estimates available for the system.}, author = {Marveggio, Alice and Schimperna, Giulio}, issn = {1090-2732}, journal = {Journal of Differential Equations}, number = {2}, pages = {924--970}, publisher = {Elsevier}, title = {{On a non-isothermal Cahn-Hilliard model based on a microforce balance}}, doi = {10.1016/j.jde.2020.10.030}, volume = {274}, 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 = {1872-6771}, 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 = {1432-0916}, 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{8817, abstract = {The paper introduces an inertial extragradient subgradient method with self-adaptive step sizes for solving equilibrium problems in real Hilbert spaces. Weak convergence of the proposed method is obtained under the condition that the bifunction is pseudomonotone and Lipchitz continuous. Linear convergence is also given when the bifunction is strongly pseudomonotone and Lipchitz continuous. Numerical implementations and comparisons with other related inertial methods are given using test problems including a real-world application to Nash–Cournot oligopolistic electricity market equilibrium model.}, author = {Shehu, Yekini and Iyiola, Olaniyi S. and Thong, Duong Viet and Van, Nguyen Thi Cam}, issn = {1432-5217}, journal = {Mathematical Methods of Operations Research}, number = {2}, pages = {213--242}, publisher = {Springer Nature}, title = {{An inertial subgradient extragradient algorithm extended to pseudomonotone equilibrium problems}}, doi = {10.1007/s00186-020-00730-w}, volume = {93}, 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 = {1476-4687}, 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 = {1879-0445}, 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{8910, abstract = {A semiconducting nanowire fully wrapped by a superconducting shell has been proposed as a platform for obtaining Majorana modes at small magnetic fields. In this study, we demonstrate that the appearance of subgap states in such structures is actually governed by the junction region in tunneling spectroscopy measurements and not the full-shell nanowire itself. Short tunneling regions never show subgap states, whereas longer junctions always do. This can be understood in terms of quantum dots forming in the junction and hosting Andreev levels in the Yu-Shiba-Rusinov regime. The intricate magnetic field dependence of the Andreev levels, through both the Zeeman and Little-Parks effects, may result in robust zero-bias peaks—features that could be easily misinterpreted as originating from Majorana zero modes but are unrelated to topological superconductivity.}, author = {Valentini, Marco and Peñaranda, Fernando and Hofmann, Andrea C and Brauns, Matthias and Hauschild, Robert and Krogstrup, Peter and San-Jose, Pablo and Prada, Elsa and Aguado, Ramón and Katsaros, Georgios}, issn = {1095-9203}, journal = {Science}, number = {6550}, publisher = {American Association for the Advancement of Science}, title = {{Nontopological zero-bias peaks in full-shell nanowires induced by flux-tunable Andreev states}}, doi = {10.1126/science.abf1513}, volume = {373}, year = {2021}, } @article{8911, abstract = {In the worldwide endeavor for disruptive quantum technologies, germanium is emerging as a versatile material to realize devices capable of encoding, processing, or transmitting quantum information. These devices leverage special properties of the germanium valence-band states, commonly known as holes, such as their inherently strong spin-orbit coupling and the ability to host superconducting pairing correlations. In this Review, we initially introduce the physics of holes in low-dimensional germanium structures with key insights from a theoretical perspective. We then examine the material science progress underpinning germanium-based planar heterostructures and nanowires. We review the most significant experimental results demonstrating key building blocks for quantum technology, such as an electrically driven universal quantum gate set with spin qubits in quantum dots and superconductor-semiconductor devices for hybrid quantum systems. We conclude by identifying the most promising prospects toward scalable quantum information processing. }, author = {Scappucci, Giordano and Kloeffel, Christoph and Zwanenburg, Floris A. and Loss, Daniel and Myronov, Maksym and Zhang, Jian-Jun and Franceschi, Silvano De and Katsaros, Georgios and Veldhorst, Menno}, issn = {2058-8437}, journal = {Nature Reviews Materials}, pages = {926–943 }, publisher = {Springer Nature}, title = {{The germanium quantum information route}}, doi = {10.1038/s41578-020-00262-z}, volume = {6}, year = {2021}, } @article{8912, abstract = {For automata, synchronization, the problem of bringing an automaton to a particular state regardless of its initial state, is important. It has several applications in practice and is related to a fifty-year-old conjecture on the length of the shortest synchronizing word. Although using shorter words increases the effectiveness in practice, finding a shortest one (which is not necessarily unique) is NP-hard. For this reason, there exist various heuristics in the literature. However, high-quality heuristics such as SynchroP producing relatively shorter sequences are very expensive and can take hours when the automaton has tens of thousands of states. The SynchroP heuristic has been frequently used as a benchmark to evaluate the performance of the new heuristics. In this work, we first improve the runtime of SynchroP and its variants by using algorithmic techniques. We then focus on adapting SynchroP for many-core architectures, and overall, we obtain more than 1000× speedup on GPUs compared to naive sequential implementation that has been frequently used as a benchmark to evaluate new heuristics in the literature. We also propose two SynchroP variants and evaluate their performance.}, author = {Sarac, Naci E and Altun, Ömer Faruk and Atam, Kamil Tolga and Karahoda, Sertac and Kaya, Kamer and Yenigün, Hüsnü}, issn = {1873-6793}, journal = {Expert Systems with Applications}, number = {4}, publisher = {Elsevier}, title = {{Boosting expensive synchronizing heuristics}}, doi = {10.1016/j.eswa.2020.114203}, volume = {167}, 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 = {1478-3231}, 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{8928, abstract = {Domestication is a human‐induced selection process that imprints the genomes of domesticated populations over a short evolutionary time scale and that occurs in a given demographic context. Reconstructing historical gene flow, effective population size changes and their timing is therefore of fundamental interest to understand how plant demography and human selection jointly shape genomic divergence during domestication. Yet, the comparison under a single statistical framework of independent domestication histories across different crop species has been little evaluated so far. Thus, it is unclear whether domestication leads to convergent demographic changes that similarly affect crop genomes. To address this question, we used existing and new transcriptome data on three crop species of Solanaceae (eggplant, pepper and tomato), together with their close wild relatives. We fitted twelve demographic models of increasing complexity on the unfolded joint allele frequency spectrum for each wild/crop pair, and we found evidence for both shared and species‐specific demographic processes between species. A convergent history of domestication with gene flow was inferred for all three species, along with evidence of strong reduction in the effective population size during the cultivation stage of tomato and pepper. The absence of any reduction in size of the crop in eggplant stands out from the classical view of the domestication process; as does the existence of a “protracted period” of management before cultivation. Our results also suggest divergent management strategies of modern cultivars among species as their current demography substantially differs. Finally, the timing of domestication is species‐specific and supported by the few historical records available.}, author = {Arnoux, Stéphanie and Fraisse, Christelle and Sauvage, Christopher}, issn = {1420-9101}, journal = {Journal of Evolutionary Biology}, number = {2}, pages = {270--283}, publisher = {Wiley}, title = {{Genomic inference of complex domestication histories in three Solanaceae species}}, doi = {10.1111/jeb.13723}, volume = {34}, year = {2021}, } @article{8940, abstract = {We quantise Whitney’s construction to prove the existence of a triangulation for any C^2 manifold, so that we get an algorithm with explicit bounds. We also give a new elementary proof, which is completely geometric.}, author = {Boissonnat, Jean-Daniel and Kachanovich, Siargey and Wintraecken, Mathijs}, issn = {1432-0444}, journal = {Discrete & Computational Geometry}, keywords = {Theoretical Computer Science, Computational Theory and Mathematics, Geometry and Topology, Discrete Mathematics and Combinatorics}, number = {1}, pages = {386--434}, publisher = {Springer Nature}, title = {{Triangulating submanifolds: An elementary and quantified version of Whitney’s method}}, doi = {10.1007/s00454-020-00250-8}, volume = {66}, 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 = {1091-6490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, 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 = {1752-9867}, 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 = {1091-6490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, 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}, }