@article{7805, abstract = {Plants as non-mobile organisms constantly integrate varying environmental signals to flexibly adapt their growth and development. Local fluctuations in water and nutrient availability, sudden changes in temperature or other abiotic and biotic stresses can trigger changes in the growth of plant organs. Multiple mutually interconnected hormonal signaling cascades act as essential endogenous translators of these exogenous signals in the adaptive responses of plants. Although the molecular backbones of hormone transduction pathways have been identified, the mechanisms underlying their interactions are largely unknown. Here, using genome wide transcriptome profiling we identify an auxin and cytokinin cross-talk component; SYNERGISTIC ON AUXIN AND CYTOKININ 1 (SYAC1), whose expression in roots is strictly dependent on both of these hormonal pathways. We show that SYAC1 is a regulator of secretory pathway, whose enhanced activity interferes with deposition of cell wall components and can fine-tune organ growth and sensitivity to soil pathogens.}, author = {Hurny, Andrej and Cuesta, Candela and Cavallari, Nicola and Ötvös, Krisztina and Duclercq, Jerome and Dokládal, Ladislav and Montesinos López, Juan C and Gallemi, Marçal and Semeradova, Hana and Rauter, Thomas and Stenzel, Irene and Persiau, Geert and Benade, Freia and Bhalearo, Rishikesh and Sýkorová, Eva and Gorzsás, András and Sechet, Julien and Mouille, Gregory and Heilmann, Ingo and De Jaeger, Geert and Ludwig-Müller, Jutta and Benková, Eva}, issn = {20411723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Synergistic on Auxin and Cytokinin 1 positively regulates growth and attenuates soil pathogen resistance}}, doi = {10.1038/s41467-020-15895-5}, volume = {11}, year = {2020}, } @article{7882, abstract = {A few-body cluster is a building block of a many-body system in a gas phase provided the temperature at most is of the order of the binding energy of this cluster. Here we illustrate this statement by considering a system of tubes filled with dipolar distinguishable particles. We calculate the partition function, which determines the probability to find a few-body cluster at a given temperature. The input for our calculations—the energies of few-body clusters—is estimated using the harmonic approximation. We first describe and demonstrate the validity of our numerical procedure. Then we discuss the results featuring melting of the zero-temperature many-body state into a gas of free particles and few-body clusters. For temperature higher than its binding energy threshold, the dimers overwhelmingly dominate the ensemble, where the remaining probability is in free particles. At very high temperatures free (harmonic oscillator trap-bound) particle dominance is eventually reached. This structure evolution appears both for one and two particles in each layer providing crucial information about the behavior of ultracold dipolar gases. The investigation addresses the transition region between few- and many-body physics as a function of temperature using a system of ten dipoles in five tubes.}, author = {Armstrong, Jeremy R. and Jensen, Aksel S. and Volosniev, Artem and Zinner, Nikolaj T.}, issn = {22277390}, journal = {Mathematics}, number = {4}, publisher = {MDPI}, title = {{Clusters in separated tubes of tilted dipoles}}, doi = {10.3390/math8040484}, volume = {8}, year = {2020}, } @article{7804, abstract = {Besides pro-inflammatory roles, the ancient cytokine interleukin-17 (IL-17) modulates neural circuit function. We investigate IL-17 signaling in neurons, and the extent it can alter organismal phenotypes. We combine immunoprecipitation and mass spectrometry to biochemically characterize endogenous signaling complexes that function downstream of IL-17 receptors in C. elegans neurons. We identify the paracaspase MALT-1 as a critical output of the pathway. MALT1 mediates signaling from many immune receptors in mammals, but was not previously implicated in IL-17 signaling or nervous system function. C. elegans MALT-1 forms a complex with homologs of Act1 and IRAK and appears to function both as a scaffold and a protease. MALT-1 is expressed broadly in the C. elegans nervous system, and neuronal IL-17–MALT-1 signaling regulates multiple phenotypes, including escape behavior, associative learning, immunity and longevity. Our data suggest MALT1 has an ancient role modulating neural circuit function downstream of IL-17 to remodel physiology and behavior.}, author = {Flynn, Sean M. and Chen, Changchun and Artan, Murat and Barratt, Stephen and Crisp, Alastair and Nelson, Geoffrey M. and Peak-Chew, Sew Yeu and Begum, Farida and Skehel, Mark and De Bono, Mario}, issn = {20411723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{MALT-1 mediates IL-17 neural signaling to regulate C. elegans behavior, immunity and longevity}}, doi = {10.1038/s41467-020-15872-y}, volume = {11}, year = {2020}, } @article{7875, abstract = {Cells navigating through complex tissues face a fundamental challenge: while multiple protrusions explore different paths, the cell needs to avoid entanglement. How a cell surveys and then corrects its own shape is poorly understood. Here, we demonstrate that spatially distinct microtubule dynamics regulate amoeboid cell migration by locally promoting the retraction of protrusions. In migrating dendritic cells, local microtubule depolymerization within protrusions remote from the microtubule organizing center triggers actomyosin contractility controlled by RhoA and its exchange factor Lfc. Depletion of Lfc leads to aberrant myosin localization, thereby causing two effects that rate-limit locomotion: (1) impaired cell edge coordination during path finding and (2) defective adhesion resolution. Compromised shape control is particularly hindering in geometrically complex microenvironments, where it leads to entanglement and ultimately fragmentation of the cell body. We thus demonstrate that microtubules can act as a proprioceptive device: they sense cell shape and control actomyosin retraction to sustain cellular coherence.}, author = {Kopf, Aglaja and Renkawitz, Jörg and Hauschild, Robert and Girkontaite, Irute and Tedford, Kerry and Merrin, Jack and Thorn-Seshold, Oliver and Trauner, Dirk and Häcker, Hans and Fischer, Klaus Dieter and Kiermaier, Eva and Sixt, Michael K}, issn = {1540-8140}, journal = {The Journal of Cell Biology}, number = {6}, publisher = {Rockefeller University Press}, title = {{Microtubules control cellular shape and coherence in amoeboid migrating cells}}, doi = {10.1083/jcb.201907154}, volume = {219}, year = {2020}, } @article{7888, abstract = {Embryonic stem cell cultures are thought to self-organize into embryoid bodies, able to undergo symmetry-breaking, germ layer specification and even morphogenesis. Yet, it is unclear how to reconcile this remarkable self-organization capacity with classical experiments demonstrating key roles for extrinsic biases by maternal factors and/or extraembryonic tissues in embryogenesis. Here, we show that zebrafish embryonic tissue explants, prepared prior to germ layer induction and lacking extraembryonic tissues, can specify all germ layers and form a seemingly complete mesendoderm anlage. Importantly, explant organization requires polarized inheritance of maternal factors from dorsal-marginal regions of the blastoderm. Moreover, induction of endoderm and head-mesoderm, which require peak Nodal-signaling levels, is highly variable in explants, reminiscent of embryos with reduced Nodal signals from the extraembryonic tissues. Together, these data suggest that zebrafish explants do not undergo bona fide self-organization, but rather display features of genetically encoded self-assembly, where intrinsic genetic programs control the emergence of order.}, author = {Schauer, Alexandra and Nunes Pinheiro, Diana C and Hauschild, Robert and Heisenberg, Carl-Philipp J}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Zebrafish embryonic explants undergo genetically encoded self-assembly}}, doi = {10.7554/elife.55190}, volume = {9}, year = {2020}, } @article{7877, abstract = {The NIPBL/MAU2 heterodimer loads cohesin onto chromatin. Mutations inNIPBLaccount for most cases ofthe rare developmental disorder Cornelia de Lange syndrome (CdLS). Here we report aMAU2 variant causing CdLS, a deletion of seven amino acids that impairs the interaction between MAU2 and the NIPBL N terminus.Investigating this interaction, we discovered that MAU2 and the NIPBL N terminus are largely dispensable fornormal cohesin and NIPBL function in cells with a NIPBL early truncating mutation. Despite a predicted fataloutcome of an out-of-frame single nucleotide duplication inNIPBL, engineered in two different cell lines,alternative translation initiation yields a form of NIPBL missing N-terminal residues. This form cannot interactwith MAU2, but binds DNA and mediates cohesin loading. Altogether, our work reveals that cohesin loading can occur independently of functional NIPBL/MAU2 complexes and highlights a novel mechanism protectiveagainst out-of-frame mutations that is potentially relevant for other genetic conditions.}, author = {Parenti, Ilaria and Diab, Farah and Gil, Sara Ruiz and Mulugeta, Eskeatnaf and Casa, Valentina and Berutti, Riccardo and Brouwer, Rutger W.W. and Dupé, Valerie and Eckhold, Juliane and Graf, Elisabeth and Puisac, Beatriz and Ramos, Feliciano and Schwarzmayr, Thomas and Gines, Macarena Moronta and Van Staveren, Thomas and Van Ijcken, Wilfred F.J. and Strom, Tim M. and Pié, Juan and Watrin, Erwan and Kaiser, Frank J. and Wendt, Kerstin S.}, issn = {22111247}, journal = {Cell Reports}, number = {7}, publisher = {Elsevier}, title = {{MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome}}, doi = {10.1016/j.celrep.2020.107647}, volume = {31}, year = {2020}, } @article{7878, abstract = {Type 1 metabotropic glutamate receptors (mGluR1s) are key elements in neuronal signaling. While their function is well documented in slices, requirements for their activation in vivo are poorly understood. We examine this question in adult mice in vivo using 2-photon imaging of cerebellar molecular layer interneurons (MLIs) expressing GCaMP. In anesthetized mice, parallel fiber activation evokes beam-like Cai rises in postsynaptic MLIs which depend on co-activation of mGluR1s and ionotropic glutamate receptors (iGluRs). In awake mice, blocking mGluR1 decreases Cai rises associated with locomotion. In vitro studies and freeze-fracture electron microscopy show that the iGluR-mGluR1 interaction is synergistic and favored by close association of the two classes of receptors. Altogether our results suggest that mGluR1s, acting in synergy with iGluRs, potently contribute to processing cerebellar neuronal signaling under physiological conditions.}, author = {Bao, Jin and Graupner, Michael and Astorga, Guadalupe and Collin, Thibault and Jalil, Abdelali and Indriati, Dwi Wahyu and Bradley, Jonathan and Shigemoto, Ryuichi and Llano, Isabel}, issn = {2050084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo}}, doi = {10.7554/eLife.56839}, volume = {9}, year = {2020}, } @article{7880, abstract = {Following its evoked release, dopamine (DA) signaling is rapidly terminated by presynaptic reuptake, mediated by the cocaine-sensitive DA transporter (DAT). DAT surface availability is dynamically regulated by endocytic trafficking, and direct protein kinase C (PKC) activation acutely diminishes DAT surface expression by accelerating DAT internalization. Previous cell line studies demonstrated that PKC-stimulated DAT endocytosis requires both Ack1 inactivation, which releases a DAT-specific endocytic brake, and the neuronal GTPase, Rit2, which binds DAT. However, it is unknown whether Rit2 is required for PKC-stimulated DAT endocytosis in DAergic terminals or whether there are region- and/or sex-dependent differences in PKC-stimulated DAT trafficking. Moreover, the mechanisms by which Rit2 controls PKC-stimulated DAT endocytosis are unknown. Here, we directly examined these important questions. Ex vivo studies revealed that PKC activation acutely decreased DAT surface expression selectively in ventral, but not dorsal, striatum. AAV-mediated, conditional Rit2 knockdown in DAergic neurons impacted baseline DAT surface:intracellular distribution in DAergic terminals from female ventral, but not dorsal, striatum. Further, Rit2 was required for PKC-stimulated DAT internalization in both male and female ventral striatum. FRET and surface pulldown studies in cell lines revealed that PKC activation drives DAT-Rit2 surface dissociation and that the DAT N terminus is required for both PKC-mediated DAT-Rit2 dissociation and DAT internalization. Finally, we found that Rit2 and Ack1 independently converge on DAT to facilitate PKC-stimulated DAT endocytosis. Together, our data provide greater insight into mechanisms that mediate PKC-regulated DAT internalization and reveal unexpected region-specific differences in PKC-stimulated DAT trafficking in bona fide DAergic terminals. }, author = {Fagan, Rita R. and Kearney, Patrick J. and Sweeney, Carolyn G. and Luethi, Dino and Schoot Uiterkamp, Florianne E and Schicker, Klaus and Alejandro, Brian S. and O'Connor, Lauren C. and Sitte, Harald H. and Melikian, Haley E.}, issn = {1083351X}, journal = {Journal of Biological Chemistry}, number = {16}, pages = {5229--5244}, publisher = {ASBMB Publications}, title = {{Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact}}, doi = {10.1074/jbc.RA120.012628}, volume = {295}, year = {2020}, } @article{7864, abstract = {Purpose of review: Cancer is one of the leading causes of death and the incidence rates are constantly rising. The heterogeneity of tumors poses a big challenge for the treatment of the disease and natural antibodies additionally affect disease progression. The introduction of engineered mAbs for anticancer immunotherapies has substantially improved progression-free and overall survival of cancer patients, but little efforts have been made to exploit other antibody isotypes than IgG. Recent findings: In order to improve these therapies, ‘next-generation antibodies’ were engineered to enhance a specific feature of classical antibodies and form a group of highly effective and precise therapy compounds. Advanced antibody approaches include among others antibody-drug conjugates, glyco-engineered and Fc-engineered antibodies, antibody fragments, radioimmunotherapy compounds, bispecific antibodies and alternative (non-IgG) immunoglobulin classes, especially IgE. Summary: The current review describes solutions for the needs of next-generation antibody therapies through different approaches. Careful selection of the best-suited engineering methodology is a key factor in developing personalized, more specific and more efficient mAbs against cancer to improve the outcomes of cancer patients. We highlight here the large evidence of IgE exploiting a highly cytotoxic effector arm as potential next-generation anticancer immunotherapy.}, author = {Singer, Judit and Singer, Josef and Jensen-Jarolim, Erika}, issn = {14736322}, journal = {Current opinion in allergy and clinical immunology}, number = {3}, pages = {282--289}, publisher = {Wolters Kluwer}, title = {{Precision medicine in clinical oncology: the journey from IgG antibody to IgE}}, doi = {10.1097/ACI.0000000000000637}, volume = {20}, year = {2020}, } @article{7876, abstract = {In contrast to lymph nodes, the lymphoid regions of the spleen—the white pulp—are located deep within the organ, yielding the trafficking paths of T cells in the white pulp largely invisible. In an intravital microscopy tour de force reported in this issue of Immunity, Chauveau et al. show that T cells perform unidirectional, perivascular migration through the enigmatic marginal zone bridging channels. }, author = {Sixt, Michael K and Lämmermann, Tim}, issn = {10974180}, journal = {Immunity}, number = {5}, pages = {721--723}, publisher = {Elsevier}, title = {{T cells: Bridge-and-channel commute to the white pulp}}, doi = {10.1016/j.immuni.2020.04.020}, volume = {52}, year = {2020}, } @article{7909, abstract = {Cell migration entails networks and bundles of actin filaments termed lamellipodia and microspikes or filopodia, respectively, as well as focal adhesions, all of which recruit Ena/VASP family members hitherto thought to antagonize efficient cell motility. However, we find these proteins to act as positive regulators of migration in different murine cell lines. CRISPR/Cas9-mediated loss of Ena/VASP proteins reduced lamellipodial actin assembly and perturbed lamellipodial architecture, as evidenced by changed network geometry as well as reduction of filament length and number that was accompanied by abnormal Arp2/3 complex and heterodimeric capping protein accumulation. Loss of Ena/VASP function also abolished the formation of microspikes normally embedded in lamellipodia, but not of filopodia capable of emanating without lamellipodia. Ena/VASP-deficiency also impaired integrin-mediated adhesion accompanied by reduced traction forces exerted through these structures. Our data thus uncover novel Ena/VASP functions of these actin polymerases that are fully consistent with their promotion of cell migration.}, author = {Damiano-Guercio, Julia and Kurzawa, Laëtitia and Müller, Jan and Dimchev, Georgi A and Schaks, Matthias and Nemethova, Maria and Pokrant, Thomas and Brühmann, Stefan and Linkner, Joern and Blanchoin, Laurent and Sixt, Michael K and Rottner, Klemens and Faix, Jan}, issn = {2050084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion}}, doi = {10.7554/eLife.55351}, volume = {9}, year = {2020}, } @article{7908, abstract = {Volatile anesthetics are widely used for surgery, but neuronal mechanisms of anesthesia remain unidentified. At the calyx of Held in brainstem slices from rats of either sex, isoflurane at clinical doses attenuated EPSCs by decreasing the release probability and the number of readily releasable vesicles. In presynaptic recordings of Ca2+ currents and exocytic capacitance changes, isoflurane attenuated exocytosis by inhibiting Ca2+ currents evoked by a short presynaptic depolarization, whereas it inhibited exocytosis evoked by a prolonged depolarization via directly blocking exocytic machinery downstream of Ca2+ influx. Since the length of presynaptic depolarization can simulate the frequency of synaptic inputs, isoflurane anesthesia is likely mediated by distinct dual mechanisms, depending on input frequencies. In simultaneous presynaptic and postsynaptic action potential recordings, isoflurane impaired the fidelity of repetitive spike transmission, more strongly at higher frequencies. Furthermore, in the cerebrum of adult mice, isoflurane inhibited monosynaptic corticocortical spike transmission, preferentially at a higher frequency. We conclude that dual presynaptic mechanisms operate for the anesthetic action of isoflurane, of which direct inhibition of exocytic machinery plays a low-pass filtering role in spike transmission at central excitatory synapses.}, author = {Wang, Han Ying and Eguchi, Kohgaku and Yamashita, Takayuki and Takahashi, Tomoyuki}, issn = {15292401}, journal = {Journal of Neuroscience}, number = {21}, pages = {4103--4115}, publisher = {Society for Neuroscience}, title = {{Frequency-dependent block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms}}, doi = {10.1523/JNEUROSCI.2946-19.2020}, volume = {40}, year = {2020}, } @article{7931, abstract = {In the course of sample preparation for Next Generation Sequencing (NGS), DNA is fragmented by various methods. Fragmentation shows a persistent bias with regard to the cleavage rates of various dinucleotides. With the exception of CpG dinucleotides the previously described biases were consistent with results of the DNA cleavage in solution. Here we computed cleavage rates of all dinucleotides including the methylated CpG and unmethylated CpG dinucleotides using data of the Whole Genome Sequencing datasets of the 1000 Genomes project. We found that the cleavage rate of CpG is significantly higher for the methylated CpG dinucleotides. Using this information, we developed a classifier for distinguishing cancer and healthy tissues based on their CpG islands statuses of the fragmentation. A simple Support Vector Machine classifier based on this algorithm shows an accuracy of 84%. The proposed method allows the detection of epigenetic markers purely based on mechanochemical DNA fragmentation, which can be detected by a simple analysis of the NGS sequencing data.}, author = {Uroshlev, Leonid A. and Abdullaev, Eldar T. and Umarova, Iren R. and Il’Icheva, Irina A. and Panchenko, Larisa A. and Polozov, Robert V. and Kondrashov, Fyodor and Nechipurenko, Yury D. and Grokhovsky, Sergei L.}, issn = {20452322}, journal = {Scientific Reports}, publisher = {Springer Nature}, title = {{A method for identification of the methylation level of CpG islands from NGS data}}, doi = {10.1038/s41598-020-65406-1}, volume = {10}, year = {2020}, } @article{7933, abstract = {We study a mobile quantum impurity, possessing internal rotational degrees of freedom, confined to a ring in the presence of a many-particle bosonic bath. By considering the recently introduced rotating polaron problem, we define the Hamiltonian and examine the energy spectrum. The weak-coupling regime is studied by means of a variational ansatz in the truncated Fock space. The corresponding spectrum indicates that there emerges a coupling between the internal and orbital angular momenta of the impurity as a consequence of the phonon exchange. We interpret the coupling as a phonon-mediated spin-orbit coupling and quantify it by using a correlation function between the internal and the orbital angular momentum operators. The strong-coupling regime is investigated within the Pekar approach, and it is shown that the correlation function of the ground state shows a kink at a critical coupling, that is explained by a sharp transition from the noninteracting state to the states that exhibit strong interaction with the surroundings. The results might find applications in such fields as spintronics or topological insulators where spin-orbit coupling is of crucial importance.}, author = {Maslov, Mikhail and Lemeshko, Mikhail and Yakaboylu, Enderalp}, issn = {24699969}, journal = {Physical Review B}, number = {18}, publisher = {American Physical Society}, title = {{Synthetic spin-orbit coupling mediated by a bosonic environment}}, doi = {10.1103/PhysRevB.101.184104}, volume = {101}, year = {2020}, } @article{7942, abstract = {An understanding of the missing antinodal electronic excitations in the pseudogap state is essential for uncovering the physics of the underdoped cuprate high-temperature superconductors1,2,3,4,5,6. The majority of high-temperature experiments performed thus far, however, have been unable to discern whether the antinodal states are rendered unobservable due to their damping or whether they vanish due to their gapping7,8,9,10,11,12,13,14,15,16,17,18. Here, we distinguish between these two scenarios by using quantum oscillations to examine whether the small Fermi surface pocket, found to occupy only 2% of the Brillouin zone in the underdoped cuprates19,20,21,22,23,24, exists in isolation against a majority of completely gapped density of states spanning the antinodes, or whether it is thermodynamically coupled to a background of ungapped antinodal states. We find that quantum oscillations associated with the small Fermi surface pocket exhibit a signature sawtooth waveform characteristic of an isolated two-dimensional Fermi surface pocket25,26,27,28,29,30,31,32. This finding reveals that the antinodal states are destroyed by a hard gap that extends over the majority of the Brillouin zone, placing strong constraints on a drastic underlying origin of quasiparticle disappearance over almost the entire Brillouin zone in the pseudogap regime7,8,9,10,11,12,13,14,15,16,17,18.}, author = {Hartstein, Máté and Hsu, Yu Te and Modic, Kimberly A and Porras, Juan and Loew, Toshinao and Tacon, Matthieu Le and Zuo, Huakun and Wang, Jinhua and Zhu, Zengwei and Chan, Mun K. and Mcdonald, Ross D. and Lonzarich, Gilbert G. and Keimer, Bernhard and Sebastian, Suchitra E. and Harrison, Neil}, issn = {17452481}, journal = {Nature Physics}, pages = {841--847}, publisher = {Springer Nature}, title = {{Hard antinodal gap revealed by quantum oscillations in the pseudogap regime of underdoped high-Tc superconductors}}, doi = {10.1038/s41567-020-0910-0}, volume = {16}, year = {2020}, } @article{7948, abstract = {In agricultural systems, nitrate is the main source of nitrogen available for plants. Besides its role as a nutrient, nitrate has been shown to act as a signal molecule for plant growth, development and stress responses. In Arabidopsis, the NRT1.1 nitrate transceptor represses lateral root (LR) development at low nitrate availability by promoting auxin basipetal transport out of the LR primordia (LRPs). In addition, our present study shows that NRT1.1 acts as a negative regulator of the TAR2 auxin biosynthetic gene expression in the root stele. This is expected to repress local auxin biosynthesis and thus to reduce acropetal auxin supply to the LRPs. Moreover, NRT1.1 also negatively affects expression of the LAX3 auxin influx carrier, thus preventing cell wall remodeling required for overlying tissues separation during LRP emergence. Both NRT1.1-mediated repression of TAR2 and LAX3 are suppressed at high nitrate availability, resulting in the nitrate induction of TAR2 and LAX3 expression that is required for optimal stimulation of LR development by nitrate. Altogether, our results indicate that the NRT1.1 transceptor coordinately controls several crucial auxin-associated processes required for LRP development, and as a consequence that NRT1.1 plays a much more integrated role than previously anticipated in regulating the nitrate response of root system architecture.}, author = {Maghiaoui, A and Bouguyon, E and Cuesta, Candela and Perrine-Walker, F and Alcon, C and Krouk, G and Benková, Eva and Nacry, P and Gojon, A and Bach, L}, issn = {1460-2431}, journal = {Journal of Experimental Botany}, number = {15}, pages = {4480--4494}, publisher = {Oxford University Press}, title = {{The Arabidopsis NRT1.1 transceptor coordinately controls auxin biosynthesis and transport to regulate root branching in response to nitrate}}, doi = {10.1093/jxb/eraa242}, volume = {71}, year = {2020}, } @article{7940, abstract = {We prove that the Yangian associated to an untwisted symmetric affine Kac–Moody Lie algebra is isomorphic to the Drinfeld double of a shuffle algebra. The latter is constructed in [YZ14] as an algebraic formalism of cohomological Hall algebras. As a consequence, we obtain the Poincare–Birkhoff–Witt (PBW) theorem for this class of affine Yangians. Another independent proof of the PBW theorem is given recently by Guay, Regelskis, and Wendlandt [GRW18].}, author = {Yang, Yaping and Zhao, Gufang}, issn = {1531586X}, journal = {Transformation Groups}, pages = {1371--1385}, publisher = {Springer Nature}, title = {{The PBW theorem for affine Yangians}}, doi = {10.1007/s00031-020-09572-6}, volume = {25}, year = {2020}, } @misc{9708, abstract = {This research data supports 'Hard antinodal gap revealed by quantum oscillations in the pseudogap regime of underdoped high-Tc superconductors'. A Readme file for plotting each figure is provided.}, author = {Hartstein, Mate and Hsu, Yu-Te and Modic, Kimberly A and Porras, Juan and Loew, Toshinao and Le Tacon, Matthieu and Zuo, Huakun and Wang, Jinhua and Zhu, Zengwei and Chan, Mun and McDonald, Ross and Lonzarich, Gilbert and Keimer, Bernhard and Sebastian, Suchitra and Harrison, Neil}, publisher = {Apollo - University of Cambridge}, title = {{Accompanying dataset for 'Hard antinodal gap revealed by quantum oscillations in the pseudogap regime of underdoped high-Tc superconductors'}}, doi = {10.17863/cam.50169}, year = {2020}, } @inproceedings{7955, abstract = {Simple stochastic games are turn-based 2½-player games with a reachability objective. The basic question asks whether one player can ensure reaching a given target with at least a given probability. A natural extension is games with a conjunction of such conditions as objective. Despite a plethora of recent results on the analysis of systems with multiple objectives, the decidability of this basic problem remains open. In this paper, we present an algorithm approximating the Pareto frontier of the achievable values to a given precision. Moreover, it is an anytime algorithm, meaning it can be stopped at any time returning the current approximation and its error bound.}, author = {Ashok, Pranav and Chatterjee, Krishnendu and Kretinsky, Jan and Weininger, Maximilian and Winkler, Tobias}, booktitle = {Proceedings of the 35th Annual ACM/IEEE Symposium on Logic in Computer Science }, isbn = {9781450371049}, location = {Saarbrücken, Germany}, pages = {102--115}, publisher = {Association for Computing Machinery}, title = {{Approximating values of generalized-reachability stochastic games}}, doi = {10.1145/3373718.3394761}, year = {2020}, } @article{7957, abstract = {Neurodevelopmental disorders (NDDs) are a class of disorders affecting brain development and function and are characterized by wide genetic and clinical variability. In this review, we discuss the multiple factors that influence the clinical presentation of NDDs, with particular attention to gene vulnerability, mutational load, and the two-hit model. Despite the complex architecture of mutational events associated with NDDs, the various proteins involved appear to converge on common pathways, such as synaptic plasticity/function, chromatin remodelers and the mammalian target of rapamycin (mTOR) pathway. A thorough understanding of the mechanisms behind these pathways will hopefully lead to the identification of candidates that could be targeted for treatment approaches.}, author = {Parenti, Ilaria and Garcia Rabaneda, Luis E and Schön, Hanna and Novarino, Gaia}, issn = {1878108X}, journal = {Trends in Neurosciences}, number = {8}, pages = {608--621}, publisher = {Elsevier}, title = {{Neurodevelopmental disorders: From genetics to functional pathways}}, doi = {10.1016/j.tins.2020.05.004}, volume = {43}, year = {2020}, } @article{7960, abstract = {Let A={A1,…,An} be a family of sets in the plane. For 0≤i2b be integers. We prove that if each k-wise or (k+1)-wise intersection of sets from A has at most b path-connected components, which all are open, then fk+1=0 implies fk≤cfk−1 for some positive constant c depending only on b and k. These results also extend to two-dimensional compact surfaces.}, author = {Kalai, Gil and Patakova, Zuzana}, issn = {14320444}, journal = {Discrete and Computational Geometry}, pages = {304--323}, publisher = {Springer Nature}, title = {{Intersection patterns of planar sets}}, doi = {10.1007/s00454-020-00205-z}, volume = {64}, year = {2020}, } @article{7962, abstract = {A string graph is the intersection graph of a family of continuous arcs in the plane. The intersection graph of a family of plane convex sets is a string graph, but not all string graphs can be obtained in this way. We prove the following structure theorem conjectured by Janson and Uzzell: The vertex set of almost all string graphs on n vertices can be partitioned into five cliques such that some pair of them is not connected by any edge (n→∞). We also show that every graph with the above property is an intersection graph of plane convex sets. As a corollary, we obtain that almost all string graphs on n vertices are intersection graphs of plane convex sets.}, author = {Pach, János and Reed, Bruce and Yuditsky, Yelena}, issn = {14320444}, journal = {Discrete and Computational Geometry}, number = {4}, pages = {888--917}, publisher = {Springer Nature}, title = {{Almost all string graphs are intersection graphs of plane convex sets}}, doi = {10.1007/s00454-020-00213-z}, volume = {63}, year = {2020}, } @article{13460, abstract = {Binary interaction can cause stellar envelopes to be stripped, which significantly reduces the radius of the star. The orbit of a binary composed of a stripped star and a compact object can therefore be so tight that the gravitational radiation the system produces reaches frequencies accessible to the Laser Interferometer Space Antenna (LISA). Two such stripped stars in tight orbits with white dwarfs are known so far (ZTF J2130+4420 and CD−30°11223), but many more are expected to exist. These binaries provide important constraints for binary evolution models and may be used as LISA verification sources. We develop a Monte Carlo code that uses detailed evolutionary models to simulate the Galactic population of stripped stars in tight orbits with either neutron star or white dwarf companions. We predict 0–100 stripped star + white dwarf binaries and 0–4 stripped star + neutron star binaries with a signal-to-noise ratio >5 after 10 yr of observations with LISA. More than 90% of these binaries are expected to show large radial velocity shifts of ≳200 $\,\mathrm{km}\,{{\rm{s}}}^{-1}$, which are spectroscopically detectable. Photometric variability due to tidal deformation of the stripped star is also expected and has been observed in ZTF J2130+4420 and CD−30°11223. In addition, the stripped star + neutron star binaries are expected to be X-ray bright with LX ≳ 1033–1036 $\,\mathrm{erg}\,{{\rm{s}}}^{-1}$. Our results show that stripped star binaries are promising multimessenger sources for the upcoming electromagnetic and gravitational wave facilities.}, author = {Götberg, Ylva Louise Linsdotter and Korol, V. and Lamberts, A. and Kupfer, T. and Breivik, K. and Ludwig, B. and Drout, M. R.}, issn = {1538-4357}, journal = {The Astrophysical Journal}, keywords = {Space and Planetary Science, Astronomy and Astrophysics}, number = {1}, publisher = {American Astronomical Society}, title = {{Stars stripped in binaries: The living gravitational-wave sources}}, doi = {10.3847/1538-4357/abbda5}, volume = {904}, year = {2020}, } @article{7999, abstract = {Linking epigenetic marks to clinical outcomes improves insight into molecular processes, disease prediction, and therapeutic target identification. Here, a statistical approach is presented to infer the epigenetic architecture of complex disease, determine the variation captured by epigenetic effects, and estimate phenotype-epigenetic probe associations jointly. Implicitly adjusting for probe correlations, data structure (cell-count or relatedness), and single-nucleotide polymorphism (SNP) marker effects, improves association estimates and in 9,448 individuals, 75.7% (95% CI 71.70–79.3) of body mass index (BMI) variation and 45.6% (95% CI 37.3–51.9) of cigarette consumption variation was captured by whole blood methylation array data. Pathway-linked probes of blood cholesterol, lipid transport and sterol metabolism for BMI, and xenobiotic stimuli response for smoking, showed >1.5 times larger associations with >95% posterior inclusion probability. Prediction accuracy improved by 28.7% for BMI and 10.2% for smoking over a LASSO model, with age-, and tissue-specificity, implying associations are a phenotypic consequence rather than causal. }, author = {Trejo Banos, D and McCartney, DL and Patxot, M and Anchieri, L and Battram, T and Christiansen, C and Costeira, R and Walker, RM and Morris, SW and Campbell, A and Zhang, Q and Porteous, DJ and McRae, AF and Wray, NR and Visscher, PM and Haley, CS and Evans, KL and Deary, IJ and McIntosh, AM and Hemani, G and Bell, JT and Marioni, RE and Robinson, Matthew Richard}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Bayesian reassessment of the epigenetic architecture of complex traits}}, doi = {10.1038/s41467-020-16520-1}, volume = {11}, year = {2020}, } @article{7995, abstract = {When divergent populations are connected by gene flow, the establishment of complete reproductive isolation usually requires the joint action of multiple barrier effects. One example where multiple barrier effects are coupled consists of a single trait that is under divergent natural selection and also mediates assortative mating. Such multiple‐effect traits can strongly reduce gene flow. However, there are few cases where patterns of assortative mating have been described quantitatively and their impact on gene flow has been determined. Two ecotypes of the coastal marine snail, Littorina saxatilis , occur in North Atlantic rocky‐shore habitats dominated by either crab predation or wave action. There is evidence for divergent natural selection acting on size, and size‐assortative mating has previously been documented. Here, we analyze the mating pattern in L. saxatilis with respect to size in intensively sampled transects across boundaries between the habitats. We show that the mating pattern is mostly conserved between ecotypes and that it generates both assortment and directional sexual selection for small male size. Using simulations, we show that the mating pattern can contribute to reproductive isolation between ecotypes but the barrier to gene flow is likely strengthened more by sexual selection than by assortment.}, author = {Perini, Samuel and Rafajlović, Marina and Westram, Anja M and Johannesson, Kerstin and Butlin, Roger K.}, issn = {15585646}, journal = {Evolution}, number = {7}, pages = {1482--1497}, publisher = {Wiley}, title = {{Assortative mating, sexual selection, and their consequences for gene flow in Littorina}}, doi = {10.1111/evo.14027}, volume = {74}, year = {2020}, } @misc{8809, abstract = {When divergent populations are connected by gene flow, the establishment of complete reproductive isolation usually requires the joint action of multiple barrier effects. One example where multiple barrier effects are coupled consists of a single trait that is under divergent natural selection and also mediates assortative mating. Such multiple-effect traits can strongly reduce gene flow. However, there are few cases where patterns of assortative mating have been described quantitatively and their impact on gene flow has been determined. Two ecotypes of the coastal marine snail, Littorina saxatilis, occur in North Atlantic rocky-shore habitats dominated by either crab predation or wave action. There is evidence for divergent natural selection acting on size, and size-assortative mating has previously been documented. Here, we analyze the mating pattern in L. saxatilis with respect to size in intensively-sampled transects across boundaries between the habitats. We show that the mating pattern is mostly conserved between ecotypes and that it generates both assortment and directional sexual selection for small male size. Using simulations, we show that the mating pattern can contribute to reproductive isolation between ecotypes but the barrier to gene flow is likely strengthened more by sexual selection than by assortment.}, author = {Perini, Samuel and Rafajlovic, Marina and Westram, Anja M and Johannesson, Kerstin and Butlin, Roger}, publisher = {Dryad}, title = {{Data from: Assortative mating, sexual selection and their consequences for gene flow in Littorina}}, doi = {10.5061/dryad.qrfj6q5cn}, year = {2020}, } @article{8001, abstract = {Post-tetanic potentiation (PTP) is an attractive candidate mechanism for hippocampus-dependent short-term memory. Although PTP has a uniquely large magnitude at hippocampal mossy fiber-CA3 pyramidal neuron synapses, it is unclear whether it can be induced by natural activity and whether its lifetime is sufficient to support short-term memory. We combined in vivo recordings from granule cells (GCs), in vitro paired recordings from mossy fiber terminals and postsynaptic CA3 neurons, and “flash and freeze” electron microscopy. PTP was induced at single synapses and showed a low induction threshold adapted to sparse GC activity in vivo. PTP was mainly generated by enlargement of the readily releasable pool of synaptic vesicles, allowing multiplicative interaction with other plasticity forms. PTP was associated with an increase in the docked vesicle pool, suggesting formation of structural “pool engrams.” Absence of presynaptic activity extended the lifetime of the potentiation, enabling prolonged information storage in the hippocampal network.}, author = {Vandael, David H and Borges Merjane, Carolina and Zhang, Xiaomin and Jonas, Peter M}, issn = {10974199}, journal = {Neuron}, number = {3}, pages = {509--521}, publisher = {Elsevier}, title = {{Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation}}, doi = {10.1016/j.neuron.2020.05.013}, volume = {107}, year = {2020}, } @article{13998, abstract = {The interaction of strong near-infrared (NIR) laser pulses with wide-bandgap dielectrics produces high harmonics in the extreme ultraviolet (XUV) wavelength range. These observations have opened up the possibility of attosecond metrology in solids, which would benefit from a precise measurement of the emission times of individual harmonics with respect to the NIR laser field. Here we show that, when high-harmonics are detected from the input surface of a magnesium oxide crystal, a bichromatic probing of the XUV emission shows a clear synchronization largely consistent with a semiclassical model of electron–hole recollisions in bulk solids. On the other hand, the bichromatic spectrogram of harmonics originating from the exit surface of the 200 μm-thick crystal is strongly modified, indicating the influence of laser field distortions during propagation. Our tracking of sub-cycle electron and hole re-collisions at XUV energies is relevant to the development of solid-state sources of attosecond pulses.}, author = {Vampa, Giulio and Lu, Jian and You, Yong Sing and Baykusheva, Denitsa Rangelova and Wu, Mengxi and Liu, Hanzhe and Schafer, Kenneth J and Gaarde, Mette B and Reis, David A and Ghimire, Shambhu}, issn = {1361-6455}, journal = {Journal of Physics B: Atomic, Molecular and Optical Physics}, keywords = {Condensed Matter Physics, Atomic and Molecular Physics, and Optics}, number = {14}, publisher = {IOP Publishing}, title = {{Attosecond synchronization of extreme ultraviolet high harmonics from crystals}}, doi = {10.1088/1361-6455/ab8e56}, volume = {53}, year = {2020}, } @article{13999, abstract = {Attosecond chronoscopy has revealed small but measurable delays in photoionization, characterized by the ejection of an electron on absorption of a single photon. Ionization-delay measurements in atomic targets provide a wealth of information about the timing of the photoelectric effect, resonances, electron correlations and transport. However, extending this approach to molecules presents challenges, such as identifying the correct ionization channels and the effect of the anisotropic molecular landscape on the measured delays. Here, we measure ionization delays from ethyl iodide around a giant dipole resonance. By using the theoretical value for the iodine atom as a reference, we disentangle the contribution from the functional ethyl group, which is responsible for the characteristic chemical reactivity of a molecule. We find a substantial additional delay caused by the presence of a functional group, which encodes the effect of the molecular potential on the departing electron. Such information is inaccessible to the conventional approach of measuring photoionization cross-sections. The results establish ionization-delay measurements as a valuable tool in investigating the electronic properties of molecules.}, author = {Biswas, Shubhadeep and Förg, Benjamin and Ortmann, Lisa and Schötz, Johannes and Schweinberger, Wolfgang and Zimmermann, Tomáš and Pi, Liangwen and Baykusheva, Denitsa Rangelova and Masood, Hafiz A. and Liontos, Ioannis and Kamal, Amgad M. and Kling, Nora G. and Alharbi, Abdullah F. and Alharbi, Meshaal and Azzeer, Abdallah M. and Hartmann, Gregor and Wörner, Hans J. and Landsman, Alexandra S. and Kling, Matthias F.}, issn = {1745-2481}, journal = {Nature Physics}, keywords = {General Physics and Astronomy}, number = {7}, pages = {778--783}, publisher = {Springer Nature}, title = {{Probing molecular environment through photoemission delays}}, doi = {10.1038/s41567-020-0887-8}, volume = {16}, year = {2020}, } @article{8038, abstract = {Microelectromechanical systems and integrated photonics provide the basis for many reliable and compact circuit elements in modern communication systems. Electro-opto-mechanical devices are currently one of the leading approaches to realize ultra-sensitive, low-loss transducers for an emerging quantum information technology. Here we present an on-chip microwave frequency converter based on a planar aluminum on silicon nitride platform that is compatible with slot-mode coupled photonic crystal cavities. We show efficient frequency conversion between two propagating microwave modes mediated by the radiation pressure interaction with a metalized dielectric nanobeam oscillator. We achieve bidirectional coherent conversion with a total device efficiency of up to ~60%, a dynamic range of 2 × 10^9 photons/s and an instantaneous bandwidth of up to 1.7 kHz. A high fidelity quantum state transfer would be possible if the drive dependent output noise of currently ~14 photons s^−1 Hz^−1 is further reduced. Such a silicon nitride based transducer is in situ reconfigurable and could be used for on-chip classical and quantum signal routing and filtering, both for microwave and hybrid microwave-optical applications.}, author = {Fink, Johannes M and Kalaee, M. and Norte, R. and Pitanti, A. and Painter, O.}, issn = {20589565}, journal = {Quantum Science and Technology}, number = {3}, publisher = {IOP Publishing}, title = {{Efficient microwave frequency conversion mediated by a photonics compatible silicon nitride nanobeam oscillator}}, doi = {10.1088/2058-9565/ab8dce}, volume = {5}, year = {2020}, } @article{8037, abstract = {Genetic perturbations that affect bacterial resistance to antibiotics have been characterized genome-wide, but how do such perturbations interact with subsequent evolutionary adaptation to the drug? Here, we show that strong epistasis between resistance mutations and systematically identified genes can be exploited to control spontaneous resistance evolution. We evolved hundreds of Escherichia coli K-12 mutant populations in parallel, using a robotic platform that tightly controls population size and selection pressure. We find a global diminishing-returns epistasis pattern: strains that are initially more sensitive generally undergo larger resistance gains. However, some gene deletion strains deviate from this general trend and curtail the evolvability of resistance, including deletions of genes for membrane transport, LPS biosynthesis, and chaperones. Deletions of efflux pump genes force evolution on inferior mutational paths, not explored in the wild type, and some of these essentially block resistance evolution. This effect is due to strong negative epistasis with resistance mutations. The identified genes and cellular functions provide potential targets for development of adjuvants that may block spontaneous resistance evolution when combined with antibiotics.}, author = {Lukacisinova, Marta and Fernando, Booshini and Bollenbach, Mark Tobias}, issn = {20411723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Highly parallel lab evolution reveals that epistasis can curb the evolution of antibiotic resistance}}, doi = {10.1038/s41467-020-16932-z}, volume = {11}, year = {2020}, } @article{8040, abstract = {The mitochondrial respiratory chain, formed by five protein complexes, utilizes energy from catabolic processes to synthesize ATP. Complex I, the first and the largest protein complex of the chain, harvests electrons from NADH to reduce quinone, while pumping protons across the mitochondrial membrane. Detailed knowledge of the working principle of such coupled charge-transfer processes remains, however, fragmentary due to bottlenecks in understanding redox-driven conformational transitions and their interplay with the hydrated proton pathways. Complex I from Thermus thermophilus encases 16 subunits with nine iron–sulfur clusters, reduced by electrons from NADH. Here, employing the latest crystal structure of T. thermophilus complex I, we have used microsecond-scale molecular dynamics simulations to study the chemo-mechanical coupling between redox changes of the iron–sulfur clusters and conformational transitions across complex I. First, we identify the redox switches within complex I, which allosterically couple the dynamics of the quinone binding pocket to the site of NADH reduction. Second, our free-energy calculations reveal that the affinity of the quinone, specifically menaquinone, for the binding-site is higher than that of its reduced, menaquinol form—a design essential for menaquinol release. Remarkably, the barriers to diffusive menaquinone dynamics are lesser than that of the more ubiquitous ubiquinone, and the naphthoquinone headgroup of the former furnishes stronger binding interactions with the pocket, favoring menaquinone for charge transport in T. thermophilus. Our computations are consistent with experimentally validated mutations and hierarchize the key residues into three functional classes, identifying new mutation targets. Third, long-range hydrogen-bond networks connecting the quinone-binding site to the transmembrane subunits are found to be responsible for proton pumping. Put together, the simulations reveal the molecular design principles linking redox reactions to quinone turnover to proton translocation in complex I.}, author = {Gupta, Chitrak and Khaniya, Umesh and Chan, Chun Kit and Dehez, Francois and Shekhar, Mrinal and Gunner, M. R. and Sazanov, Leonid A and Chipot, Christophe and Singharoy, Abhishek}, issn = {15205126}, journal = {Journal of the American Chemical Society}, number = {20}, pages = {9220--9230}, publisher = {American Chemical Society}, title = {{Charge transfer and chemo-mechanical coupling in respiratory complex I}}, doi = {10.1021/jacs.9b13450}, volume = {142}, year = {2020}, } @article{8036, abstract = {When tiny soft ferromagnetic particles are placed along a liquid interface and exposed to a vertical magnetic field, the balance between capillary attraction and magnetic repulsion leads to self-organization into well-defined patterns. Here, we demonstrate experimentally that precessing magnetic fields induce metachronal waves on the periphery of these assemblies, similar to the ones observed in ciliates and some arthropods. The outermost layer of particles behaves like an array of cilia or legs whose sequential movement causes a net and controllable locomotion. This bioinspired many-particle swimming strategy is effective even at low Reynolds number, using only spatially uniform fields to generate the waves.}, author = {Collard, Ylona and Grosjean, Galien M and Vandewalle, Nicolas}, issn = {23993650}, journal = {Communications Physics}, publisher = {Springer Nature}, title = {{Magnetically powered metachronal waves induce locomotion in self-assemblies}}, doi = {10.1038/s42005-020-0380-9}, volume = {3}, year = {2020}, } @article{8043, abstract = {With decreasing Reynolds number, Re, turbulence in channel flow becomes spatio-temporally intermittent and self-organises into solitary stripes oblique to the mean flow direction. We report here the existence of localised nonlinear travelling wave solutions of the Navier–Stokes equations possessing this obliqueness property. Such solutions are identified numerically using edge tracking coupled with arclength continuation. All solutions emerge in saddle-node bifurcations at values of Re lower than the non-localised solutions. Relative periodic orbit solutions bifurcating from branches of travelling waves have also been computed. A complete parametric study is performed, including their stability, the investigation of their large-scale flow, and the robustness to changes of the numerical domain.}, author = {Paranjape, Chaitanya S and Duguet, Yohann and Hof, Björn}, issn = {14697645}, journal = {Journal of Fluid Mechanics}, publisher = {Cambridge University Press}, title = {{Oblique stripe solutions of channel flow}}, doi = {10.1017/jfm.2020.322}, volume = {897}, year = {2020}, } @misc{9326, abstract = {The mitochondrial respiratory chain, formed by five protein complexes, utilizes energy from catabolic processes to synthesize ATP. Complex I, the first and the largest protein complex of the chain, harvests electrons from NADH to reduce quinone, while pumping protons across the mitochondrial membrane. Detailed knowledge of the working principle of such coupled charge-transfer processes remains, however, fragmentary due to bottlenecks in understanding redox-driven conformational transitions and their interplay with the hydrated proton pathways. Complex I from Thermus thermophilus encases 16 subunits with nine iron–sulfur clusters, reduced by electrons from NADH. Here, employing the latest crystal structure of T. thermophilus complex I, we have used microsecond-scale molecular dynamics simulations to study the chemo-mechanical coupling between redox changes of the iron–sulfur clusters and conformational transitions across complex I. First, we identify the redox switches within complex I, which allosterically couple the dynamics of the quinone binding pocket to the site of NADH reduction. Second, our free-energy calculations reveal that the affinity of the quinone, specifically menaquinone, for the binding-site is higher than that of its reduced, menaquinol forma design essential for menaquinol release. Remarkably, the barriers to diffusive menaquinone dynamics are lesser than that of the more ubiquitous ubiquinone, and the naphthoquinone headgroup of the former furnishes stronger binding interactions with the pocket, favoring menaquinone for charge transport in T. thermophilus. Our computations are consistent with experimentally validated mutations and hierarchize the key residues into three functional classes, identifying new mutation targets. Third, long-range hydrogen-bond networks connecting the quinone-binding site to the transmembrane subunits are found to be responsible for proton pumping. Put together, the simulations reveal the molecular design principles linking redox reactions to quinone turnover to proton translocation in complex I.}, author = {Gupta, Chitrak and Khaniya, Umesh and Chan, Chun and Dehez, Francois and Shekhar, Mrinal and Gunner, M. R. and Sazanov, Leonid A and Chipot, Christophe and Singharoy, Abhishek}, publisher = {American Chemical Society}, title = {{Charge transfer and chemo-mechanical coupling in respiratory complex I}}, doi = {10.1021/jacs.9b13450.s002}, year = {2020}, } @article{8042, abstract = {We consider systems of N bosons in a box of volume one, interacting through a repulsive two-body potential of the form κN3β−1V(Nβx). For all 0<β<1, and for sufficiently small coupling constant κ>0, we establish the validity of Bogolyubov theory, identifying the ground state energy and the low-lying excitation spectrum up to errors that vanish in the limit of large N.}, author = {Boccato, Chiara and Brennecke, Christian and Cenatiempo, Serena and Schlein, Benjamin}, issn = {14359855}, journal = {Journal of the European Mathematical Society}, number = {7}, pages = {2331--2403}, publisher = {European Mathematical Society}, title = {{The excitation spectrum of Bose gases interacting through singular potentials}}, doi = {10.4171/JEMS/966}, volume = {22}, year = {2020}, } @misc{9713, abstract = {Additional analyses of the trajectories}, author = {Gupta, Chitrak and Khaniya, Umesh and Chan, Chun Kit and Dehez, Francois and Shekhar, Mrinal and Gunner, M.R. and Sazanov, Leonid A and Chipot, Christophe and Singharoy, Abhishek}, publisher = {American Chemical Society }, title = {{Supporting information}}, doi = {10.1021/jacs.9b13450.s001}, year = {2020}, } @misc{9878, author = {Gupta, Chitrak and Khaniya, Umesh and Chan, Chun Kit and Dehez, Francois and Shekhar, Mrinal and Gunner, M.R. and Sazanov, Leonid A and Chipot, Christophe and Singharoy, Abhishek}, publisher = {American Chemical Society}, title = {{Movies}}, doi = {10.1021/jacs.9b13450.s002}, year = {2020}, } @article{8093, abstract = {Background: The activation of the EGFR/Ras-signalling pathway in tumour cells induces a distinct chemokine repertoire, which in turn modulates the tumour microenvironment. Methods: The effects of EGFR/Ras on the expression and translation of CCL20 were analysed in a large set of epithelial cancer cell lines and tumour tissues by RT-qPCR and ELISA in vitro. CCL20 production was verified by immunohistochemistry in different tumour tissues and correlated with clinical data. The effects of CCL20 on endothelial cell migration and tumour-associated vascularisation were comprehensively analysed with chemotaxis assays in vitro and in CCR6-deficient mice in vivo. Results: Tumours facilitate progression by the EGFR/Ras-induced production of CCL20. Expression of the chemokine CCL20 in tumours correlates with advanced tumour stage, increased lymph node metastasis and decreased survival in patients. Microvascular endothelial cells abundantly express the specific CCL20 receptor CCR6. CCR6 signalling in endothelial cells induces angiogenesis. CCR6-deficient mice show significantly decreased tumour growth and tumour-associated vascularisation. The observed phenotype is dependent on CCR6 deficiency in stromal cells but not within the immune system. Conclusion: We propose that the chemokine axis CCL20–CCR6 represents a novel and promising target to interfere with the tumour microenvironment, and opens an innovative multimodal strategy for cancer therapy.}, author = {Hippe, Andreas and Braun, Stephan Alexander and Oláh, Péter and Gerber, Peter Arne and Schorr, Anne and Seeliger, Stephan and Holtz, Stephanie and Jannasch, Katharina and Pivarcsi, Andor and Buhren, Bettina and Schrumpf, Holger and Kislat, Andreas and Bünemann, Erich and Steinhoff, Martin and Fischer, Jens and Lira, Sérgio A. and Boukamp, Petra and Hevezi, Peter and Stoecklein, Nikolas Hendrik and Hoffmann, Thomas and Alves, Frauke and Sleeman, Jonathan and Bauer, Thomas and Klufa, Jörg and Amberg, Nicole and Sibilia, Maria and Zlotnik, Albert and Müller-Homey, Anja and Homey, Bernhard}, issn = {1532-1827}, journal = {British Journal of Cancer}, pages = {942--954}, publisher = {Springer Nature}, title = {{EGFR/Ras-induced CCL20 production modulates the tumour microenvironment}}, doi = {10.1038/s41416-020-0943-2}, volume = {123}, year = {2020}, } @article{8091, abstract = {In the setting of the fractional quantum Hall effect we study the effects of strong, repulsive two-body interaction potentials of short range. We prove that Haldane’s pseudo-potential operators, including their pre-factors, emerge as mathematically rigorous limits of such interactions when the range of the potential tends to zero while its strength tends to infinity. In a common approach the interaction potential is expanded in angular momentum eigenstates in the lowest Landau level, which amounts to taking the pre-factors to be the moments of the potential. Such a procedure is not appropriate for very strong interactions, however, in particular not in the case of hard spheres. We derive the formulas valid in the short-range case, which involve the scattering lengths of the interaction potential in different angular momentum channels rather than its moments. Our results hold for bosons and fermions alike and generalize previous results in [6], which apply to bosons in the lowest angular momentum channel. Our main theorem asserts the convergence in a norm-resolvent sense of the Hamiltonian on the whole Hilbert space, after appropriate energy scalings, to Hamiltonians with contact interactions in the lowest Landau level.}, author = {Seiringer, Robert and Yngvason, Jakob}, issn = {15729613}, journal = {Journal of Statistical Physics}, pages = {448--464}, publisher = {Springer}, title = {{Emergence of Haldane pseudo-potentials in systems with short-range interactions}}, doi = {10.1007/s10955-020-02586-0}, volume = {181}, year = {2020}, } @article{8077, abstract = {The projection methods with vanilla inertial extrapolation step for variational inequalities have been of interest to many authors recently due to the improved convergence speed contributed by the presence of inertial extrapolation step. However, it is discovered that these projection methods with inertial steps lose the Fejér monotonicity of the iterates with respect to the solution, which is being enjoyed by their corresponding non-inertial projection methods for variational inequalities. This lack of Fejér monotonicity makes projection methods with vanilla inertial extrapolation step for variational inequalities not to converge faster than their corresponding non-inertial projection methods at times. Also, it has recently been proved that the projection methods with vanilla inertial extrapolation step may provide convergence rates that are worse than the classical projected gradient methods for strongly convex functions. In this paper, we introduce projection methods with alternated inertial extrapolation step for solving variational inequalities. We show that the sequence of iterates generated by our methods converges weakly to a solution of the variational inequality under some appropriate conditions. The Fejér monotonicity of even subsequence is recovered in these methods and linear rate of convergence is obtained. The numerical implementations of our methods compared with some other inertial projection methods show that our method is more efficient and outperforms some of these inertial projection methods.}, author = {Shehu, Yekini and Iyiola, Olaniyi S.}, issn = {0168-9274}, journal = {Applied Numerical Mathematics}, pages = {315--337}, publisher = {Elsevier}, title = {{Projection methods with alternating inertial steps for variational inequalities: Weak and linear convergence}}, doi = {10.1016/j.apnum.2020.06.009}, volume = {157}, year = {2020}, } @article{8039, abstract = {In the present work, we report a solution-based strategy to produce crystallographically textured SnSe bulk nanomaterials and printed layers with optimized thermoelectric performance in the direction normal to the substrate. Our strategy is based on the formulation of a molecular precursor that can be continuously decomposed to produce a SnSe powder or printed into predefined patterns. The precursor formulation and decomposition conditions are optimized to produce pure phase 2D SnSe nanoplates. The printed layer and the bulk material obtained after hot press displays a clear preferential orientation of the crystallographic domains, resulting in an ultralow thermal conductivity of 0.55 W m–1 K–1 in the direction normal to the substrate. Such textured nanomaterials present highly anisotropic properties with the best thermoelectric performance in plane, i.e., in the directions parallel to the substrate, which coincide with the crystallographic bc plane of SnSe. This is an unfortunate characteristic because thermoelectric devices are designed to create/harvest temperature gradients in the direction normal to the substrate. We further demonstrate that this limitation can be overcome with the introduction of small amounts of tellurium in the precursor. The presence of tellurium allows one to reduce the band gap and increase both the charge carrier concentration and the mobility, especially the cross plane, with a minimal decrease of the Seebeck coefficient. These effects translate into record out of plane ZT values at 800 K.}, author = {Zhang, Yu and Liu, Yu and Xing, Congcong and Zhang, Ting and Li, Mengyao and Pacios, Mercè and Yu, Xiaoting and Arbiol, Jordi and Llorca, Jordi and Cadavid, Doris and Ibáñez, Maria and Cabot, Andreu}, issn = {19448252}, journal = {ACS Applied Materials and Interfaces}, number = {24}, pages = {27104--27111}, publisher = {American Chemical Society}, title = {{Tin selenide molecular precursor for the solution processing of thermoelectric materials and devices}}, doi = {10.1021/acsami.0c04331}, volume = {12}, year = {2020}, } @article{8133, abstract = {The molecular factors which control circulating levels of inflammatory proteins are not well understood. Furthermore, association studies between molecular probes and human traits are often performed by linear model-based methods which may fail to account for complex structure and interrelationships within molecular datasets.In this study, we perform genome- and epigenome-wide association studies (GWAS/EWAS) on the levels of 70 plasma-derived inflammatory protein biomarkers in healthy older adults (Lothian Birth Cohort 1936; n = 876; Olink® inflammation panel). We employ a Bayesian framework (BayesR+) which can account for issues pertaining to data structure and unknown confounding variables (with sensitivity analyses using ordinary least squares- (OLS) and mixed model-based approaches). We identified 13 SNPs associated with 13 proteins (n = 1 SNP each) concordant across OLS and Bayesian methods. We identified 3 CpG sites spread across 3 proteins (n = 1 CpG each) that were concordant across OLS, mixed-model and Bayesian analyses. Tagged genetic variants accounted for up to 45% of variance in protein levels (for MCP2, 36% of variance alone attributable to 1 polymorphism). Methylation data accounted for up to 46% of variation in protein levels (for CXCL10). Up to 66% of variation in protein levels (for VEGFA) was explained using genetic and epigenetic data combined. We demonstrated putative causal relationships between CD6 and IL18R1 with inflammatory bowel disease and between IL12B and Crohn’s disease. Our data may aid understanding of the molecular regulation of the circulating inflammatory proteome as well as causal relationships between inflammatory mediators and disease.}, author = {Hillary, Robert F. and Trejo-Banos, Daniel and Kousathanas, Athanasios and Mccartney, Daniel L. and Harris, Sarah E. and Stevenson, Anna J. and Patxot, Marion and Ojavee, Sven Erik and Zhang, Qian and Liewald, David C. and Ritchie, Craig W. and Evans, Kathryn L. and Tucker-Drob, Elliot M. and Wray, Naomi R. and Mcrae, Allan F. and Visscher, Peter M. and Deary, Ian J. and Robinson, Matthew Richard and Marioni, Riccardo E.}, issn = {1756994X}, journal = {Genome Medicine}, number = {1}, publisher = {Springer Nature}, title = {{Multi-method genome- and epigenome-wide studies of inflammatory protein levels in healthy older adults}}, doi = {10.1186/s13073-020-00754-1}, volume = {12}, year = {2020}, } @article{8127, abstract = {Mechanistic modeling in neuroscience aims to explain observed phenomena in terms of underlying causes. However, determining which model parameters agree with complex and stochastic neural data presents a significant challenge. We address this challenge with a machine learning tool which uses deep neural density estimators—trained using model simulations—to carry out Bayesian inference and retrieve the full space of parameters compatible with raw data or selected data features. Our method is scalable in parameters and data features and can rapidly analyze new data after initial training. We demonstrate the power and flexibility of our approach on receptive fields, ion channels, and Hodgkin–Huxley models. We also characterize the space of circuit configurations giving rise to rhythmic activity in the crustacean stomatogastric ganglion, and use these results to derive hypotheses for underlying compensation mechanisms. Our approach will help close the gap between data-driven and theory-driven models of neural dynamics.}, author = {Gonçalves, Pedro J. and Lueckmann, Jan-Matthis and Deistler, Michael and Nonnenmacher, Marcel and Öcal, Kaan and Bassetto, Giacomo and Chintaluri, Chaitanya and Podlaski, William F. and Haddad, Sara A. and Vogels, Tim P and Greenberg, David S. and Macke, Jakob H.}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Training deep neural density estimators to identify mechanistic models of neural dynamics}}, doi = {10.7554/eLife.56261}, volume = {9}, year = {2020}, } @article{8126, abstract = {Cortical areas comprise multiple types of inhibitory interneurons with stereotypical connectivity motifs, but their combined effect on postsynaptic dynamics has been largely unexplored. Here, we analyse the response of a single postsynaptic model neuron receiving tuned excitatory connections alongside inhibition from two plastic populations. Depending on the inhibitory plasticity rule, synapses remain unspecific (flat), become anti-correlated to, or mirror excitatory synapses. Crucially, the neuron’s receptive field, i.e., its response to presynaptic stimuli, depends on the modulatory state of inhibition. When both inhibitory populations are active, inhibition balances excitation, resulting in uncorrelated postsynaptic responses regardless of the inhibitory tuning profiles. Modulating the activity of a given inhibitory population produces strong correlations to either preferred or non-preferred inputs, in line with recent experimental findings showing dramatic context-dependent changes of neurons’ receptive fields. We thus confirm that a neuron’s receptive field doesn’t follow directly from the weight profiles of its presynaptic afferents.}, author = {Agnes, Everton J. and Luppi, Andrea I. and Vogels, Tim P}, issn = {1529-2401}, journal = {The Journal of Neuroscience}, number = {50}, pages = {9634--9649}, publisher = {Society for Neuroscience}, title = {{Complementary inhibitory weight profiles emerge from plasticity and allow attentional switching of receptive fields}}, doi = {10.1523/JNEUROSCI.0276-20.2020}, volume = {40}, year = {2020}, } @article{8132, abstract = {The WAVE regulatory complex (WRC) is crucial for assembly of the peripheral branched actin network constituting one of the main drivers of eukaryotic cell migration. Here, we uncover an essential role of the hematopoietic-specific WRC component HEM1 for immune cell development. Germline-encoded HEM1 deficiency underlies an inborn error of immunity with systemic autoimmunity, at cellular level marked by WRC destabilization, reduced filamentous actin, and failure to assemble lamellipodia. Hem1−/− mice display systemic autoimmunity, phenocopying the human disease. In the absence of Hem1, B cells become deprived of extracellular stimuli necessary to maintain the strength of B cell receptor signaling at a level permissive for survival of non-autoreactive B cells. This shifts the balance of B cell fate choices toward autoreactive B cells and thus autoimmunity.}, author = {Salzer, Elisabeth and Zoghi, Samaneh and Kiss, Máté G. and Kage, Frieda and Rashkova, Christina and Stahnke, Stephanie and Haimel, Matthias and Platzer, René and Caldera, Michael and Ardy, Rico Chandra and Hoeger, Birgit and Block, Jana and Medgyesi, David and Sin, Celine and Shahkarami, Sepideh and Kain, Renate and Ziaee, Vahid and Hammerl, Peter and Bock, Christoph and Menche, Jörg and Dupré, Loïc and Huppa, Johannes B. and Sixt, Michael K and Lomakin, Alexis and Rottner, Klemens and Binder, Christoph J. and Stradal, Theresia E.B. and Rezaei, Nima and Boztug, Kaan}, issn = {24709468}, journal = {Science Immunology}, number = {49}, publisher = {AAAS}, title = {{The cytoskeletal regulator HEM1 governs B cell development and prevents autoimmunity}}, doi = {10.1126/sciimmunol.abc3979}, volume = {5}, year = {2020}, } @misc{9706, abstract = {Additional file 2: Supplementary Tables. The association of pre-adjusted protein levels with biological and technical covariates. Protein levels were adjusted for age, sex, array plate and four genetic principal components (population structure) prior to analyses. Significant associations are emboldened. (Table S1). pQTLs associated with inflammatory biomarker levels from Bayesian penalised regression model (Posterior Inclusion Probability > 95%). (Table S2). All pQTLs associated with inflammatory biomarker levels from ordinary least squares regression model (P < 7.14 × 10− 10). (Table S3). Summary of lambda values relating to ordinary least squares GWAS and EWAS performed on inflammatory protein levels (n = 70) in Lothian Birth Cohort 1936 study. (Table S4). Conditionally significant pQTLs associated with inflammatory biomarker levels from ordinary least squares regression model (P < 7.14 × 10− 10). (Table S5). Comparison of variance explained by ordinary least squares and Bayesian penalised regression models for concordantly identified SNPs. (Table S6). Estimate of heritability for blood protein levels as well as proportion of variance explained attributable to different prior mixtures. (Table S7). Comparison of heritability estimates from Ahsan et al. (maximum likelihood) and Hillary et al. (Bayesian penalised regression). (Table S8). List of concordant SNPs identified by linear model and Bayesian penalised regression and whether they have been previously identified as eQTLs. (Table S9). Bayesian tests of colocalisation for cis pQTLs and cis eQTLs. (Table S10). Sherlock algorithm: Genes whose expression are putatively associated with circulating inflammatory proteins that harbour pQTLs. (Table S11). CpGs associated with inflammatory protein biomarkers as identified by Bayesian model (Bayesian model; Posterior Inclusion Probability > 95%). (Table S12). CpGs associated with inflammatory protein biomarkers as identified by linear model (limma) at P < 5.14 × 10− 10. (Table S13). CpGs associated with inflammatory protein biomarkers as identified by mixed linear model (OSCA) at P < 5.14 × 10− 10. (Table S14). Estimate of variance explained for blood protein levels by DNA methylation as well as proportion of explained attributable to different prior mixtures - BayesR+. (Table S15). Comparison of variance in protein levels explained by genome-wide DNA methylation data by mixed linear model (OSCA) and Bayesian penalised regression model (BayesR+). (Table S16). Variance in circulating inflammatory protein biomarker levels explained by common genetic and methylation data (joint and conditional estimates from BayesR+). Ordered by combined variance explained by genetic and epigenetic data - smallest to largest. Significant results from t-tests comparing distributions for variance explained by methylation or genetics alone versus combined estimate are emboldened. (Table S17). Genetic and epigenetic factors identified by BayesR+ when conditioning on all SNPs and CpGs together. (Table S18). Mendelian Randomisation analyses to assess whether proteins with concordantly identified genetic signals are causally associated with Alzheimer’s disease risk. (Table S19).}, author = {Hillary, Robert F. and Trejo-Banos, Daniel and Kousathanas, Athanasios and McCartney, Daniel L. and Harris, Sarah E. and Stevenson, Anna J. and Patxot, Marion and Ojavee, Sven Erik and Zhang, Qian and Liewald, David C. and Ritchie, Craig W. and Evans, Kathryn L. and Tucker-Drob, Elliot M. and Wray, Naomi R. and McRae, Allan F. and Visscher, Peter M. and Deary, Ian J. and Robinson, Matthew Richard and Marioni, Riccardo E. }, publisher = {Springer Nature}, title = {{Additional file 2 of multi-method genome- and epigenome-wide studies of inflammatory protein levels in healthy older adults}}, doi = {10.6084/m9.figshare.12629697.v1}, year = {2020}, } @article{8134, abstract = {We prove an upper bound on the free energy of a two-dimensional homogeneous Bose gas in the thermodynamic limit. We show that for a2ρ ≪ 1 and βρ ≳ 1, the free energy per unit volume differs from the one of the non-interacting system by at most 4πρ2|lna2ρ|−1(2−[1−βc/β]2+) to leading order, where a is the scattering length of the two-body interaction potential, ρ is the density, β is the inverse temperature, and βc is the inverse Berezinskii–Kosterlitz–Thouless critical temperature for superfluidity. In combination with the corresponding matching lower bound proved by Deuchert et al. [Forum Math. Sigma 8, e20 (2020)], this shows equality in the asymptotic expansion.}, author = {Mayer, Simon and Seiringer, Robert}, issn = {00222488}, journal = {Journal of Mathematical Physics}, number = {6}, publisher = {AIP Publishing}, title = {{The free energy of the two-dimensional dilute Bose gas. II. Upper bound}}, doi = {10.1063/5.0005950}, volume = {61}, year = {2020}, } @article{8112, author = {Barton, Nicholas H}, issn = {1471-2970}, journal = {Philosophical Transactions of the Royal Society. Series B: Biological Sciences}, number = {1806}, publisher = {The Royal Society}, title = {{On the completion of speciation}}, doi = {10.1098/rstb.2019.0530}, volume = {375}, year = {2020}, } @article{8162, abstract = {In mammalian genomes, a subset of genes is regulated by genomic imprinting, resulting in silencing of one parental allele. Imprinting is essential for cerebral cortex development, but prevalence and functional impact in individual cells is unclear. Here, we determined allelic expression in cortical cell types and established a quantitative platform to interrogate imprinting in single cells. We created cells with uniparental chromosome disomy (UPD) containing two copies of either the maternal or the paternal chromosome; hence, imprinted genes will be 2-fold overexpressed or not expressed. By genetic labeling of UPD, we determined cellular phenotypes and transcriptional responses to deregulated imprinted gene expression at unprecedented single-cell resolution. We discovered an unexpected degree of cell-type specificity and a novel function of imprinting in the regulation of cortical astrocyte survival. More generally, our results suggest functional relevance of imprinted gene expression in glial astrocyte lineage and thus for generating cortical cell-type diversity.}, author = {Laukoter, Susanne and Pauler, Florian and Beattie, Robert J and Amberg, Nicole and Hansen, Andi H and Streicher, Carmen and Penz, Thomas and Bock, Christoph and Hippenmeyer, Simon}, issn = {0896-6273}, journal = {Neuron}, number = {6}, pages = {1160--1179.e9}, publisher = {Elsevier}, title = {{Cell-type specificity of genomic imprinting in cerebral cortex}}, doi = {10.1016/j.neuron.2020.06.031}, volume = {107}, year = {2020}, }