TY - JOUR AB - 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. AU - Hurny, Andrej AU - Cuesta, Candela AU - Cavallari, Nicola AU - Ötvös, Krisztina AU - Duclercq, Jerome AU - Dokládal, Ladislav AU - Montesinos López, Juan C AU - Gallemi, Marçal AU - Semeradova, Hana AU - Rauter, Thomas AU - Stenzel, Irene AU - Persiau, Geert AU - Benade, Freia AU - Bhalearo, Rishikesh AU - Sýkorová, Eva AU - Gorzsás, András AU - Sechet, Julien AU - Mouille, Gregory AU - Heilmann, Ingo AU - De Jaeger, Geert AU - Ludwig-Müller, Jutta AU - Benková, Eva ID - 7805 JF - Nature Communications TI - Synergistic on Auxin and Cytokinin 1 positively regulates growth and attenuates soil pathogen resistance VL - 11 ER - TY - JOUR AB - 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. AU - Armstrong, Jeremy R. AU - Jensen, Aksel S. AU - Volosniev, Artem AU - Zinner, Nikolaj T. ID - 7882 IS - 4 JF - Mathematics TI - Clusters in separated tubes of tilted dipoles VL - 8 ER - TY - JOUR AB - 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. AU - Flynn, Sean M. AU - Chen, Changchun AU - Artan, Murat AU - Barratt, Stephen AU - Crisp, Alastair AU - Nelson, Geoffrey M. AU - Peak-Chew, Sew Yeu AU - Begum, Farida AU - Skehel, Mark AU - De Bono, Mario ID - 7804 JF - Nature Communications TI - MALT-1 mediates IL-17 neural signaling to regulate C. elegans behavior, immunity and longevity VL - 11 ER - TY - JOUR AB - 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. AU - Kopf, Aglaja AU - Renkawitz, Jörg AU - Hauschild, Robert AU - Girkontaite, Irute AU - Tedford, Kerry AU - Merrin, Jack AU - Thorn-Seshold, Oliver AU - Trauner, Dirk AU - Häcker, Hans AU - Fischer, Klaus Dieter AU - Kiermaier, Eva AU - Sixt, Michael K ID - 7875 IS - 6 JF - The Journal of Cell Biology TI - Microtubules control cellular shape and coherence in amoeboid migrating cells VL - 219 ER - TY - JOUR AB - 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. AU - Schauer, Alexandra AU - Nunes Pinheiro, Diana C AU - Hauschild, Robert AU - Heisenberg, Carl-Philipp J ID - 7888 JF - eLife SN - 2050-084X TI - Zebrafish embryonic explants undergo genetically encoded self-assembly VL - 9 ER - TY - JOUR AB - 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. AU - Parenti, Ilaria AU - Diab, Farah AU - Gil, Sara Ruiz AU - Mulugeta, Eskeatnaf AU - Casa, Valentina AU - Berutti, Riccardo AU - Brouwer, Rutger W.W. AU - Dupé, Valerie AU - Eckhold, Juliane AU - Graf, Elisabeth AU - Puisac, Beatriz AU - Ramos, Feliciano AU - Schwarzmayr, Thomas AU - Gines, Macarena Moronta AU - Van Staveren, Thomas AU - Van Ijcken, Wilfred F.J. AU - Strom, Tim M. AU - Pié, Juan AU - Watrin, Erwan AU - Kaiser, Frank J. AU - Wendt, Kerstin S. ID - 7877 IS - 7 JF - Cell Reports TI - MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome VL - 31 ER - TY - JOUR AB - 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. AU - Bao, Jin AU - Graupner, Michael AU - Astorga, Guadalupe AU - Collin, Thibault AU - Jalil, Abdelali AU - Indriati, Dwi Wahyu AU - Bradley, Jonathan AU - Shigemoto, Ryuichi AU - Llano, Isabel ID - 7878 JF - eLife TI - Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo VL - 9 ER - TY - JOUR AB - 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. AU - Fagan, Rita R. AU - Kearney, Patrick J. AU - Sweeney, Carolyn G. AU - Luethi, Dino AU - Schoot Uiterkamp, Florianne E AU - Schicker, Klaus AU - Alejandro, Brian S. AU - O'Connor, Lauren C. AU - Sitte, Harald H. AU - Melikian, Haley E. ID - 7880 IS - 16 JF - Journal of Biological Chemistry SN - 00219258 TI - Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact VL - 295 ER - TY - JOUR AB - 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. AU - Singer, Judit AU - Singer, Josef AU - Jensen-Jarolim, Erika ID - 7864 IS - 3 JF - Current opinion in allergy and clinical immunology TI - Precision medicine in clinical oncology: the journey from IgG antibody to IgE VL - 20 ER - TY - JOUR AB - 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. AU - Sixt, Michael K AU - Lämmermann, Tim ID - 7876 IS - 5 JF - Immunity SN - 10747613 TI - T cells: Bridge-and-channel commute to the white pulp VL - 52 ER - TY - JOUR AB - 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. AU - Damiano-Guercio, Julia AU - Kurzawa, Laëtitia AU - Müller, Jan AU - Dimchev, Georgi A AU - Schaks, Matthias AU - Nemethova, Maria AU - Pokrant, Thomas AU - Brühmann, Stefan AU - Linkner, Joern AU - Blanchoin, Laurent AU - Sixt, Michael K AU - Rottner, Klemens AU - Faix, Jan ID - 7909 JF - eLife TI - Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion VL - 9 ER - TY - JOUR AB - 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. AU - Wang, Han Ying AU - Eguchi, Kohgaku AU - Yamashita, Takayuki AU - Takahashi, Tomoyuki ID - 7908 IS - 21 JF - Journal of Neuroscience TI - Frequency-dependent block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms VL - 40 ER - TY - JOUR AB - 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. AU - Uroshlev, Leonid A. AU - Abdullaev, Eldar T. AU - Umarova, Iren R. AU - Il’Icheva, Irina A. AU - Panchenko, Larisa A. AU - Polozov, Robert V. AU - Kondrashov, Fyodor AU - Nechipurenko, Yury D. AU - Grokhovsky, Sergei L. ID - 7931 JF - Scientific Reports TI - A method for identification of the methylation level of CpG islands from NGS data VL - 10 ER - TY - JOUR AB - 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. AU - Maslov, Mikhail AU - Lemeshko, Mikhail AU - Yakaboylu, Enderalp ID - 7933 IS - 18 JF - Physical Review B SN - 24699950 TI - Synthetic spin-orbit coupling mediated by a bosonic environment VL - 101 ER - TY - JOUR AB - 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. AU - Hartstein, Máté AU - Hsu, Yu Te AU - Modic, Kimberly A AU - Porras, Juan AU - Loew, Toshinao AU - Tacon, Matthieu Le AU - Zuo, Huakun AU - Wang, Jinhua AU - Zhu, Zengwei AU - Chan, Mun K. AU - Mcdonald, Ross D. AU - Lonzarich, Gilbert G. AU - Keimer, Bernhard AU - Sebastian, Suchitra E. AU - Harrison, Neil ID - 7942 JF - Nature Physics SN - 17452473 TI - Hard antinodal gap revealed by quantum oscillations in the pseudogap regime of underdoped high-Tc superconductors VL - 16 ER - TY - JOUR AB - 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. AU - Maghiaoui, A AU - Bouguyon, E AU - Cuesta, Candela AU - Perrine-Walker, F AU - Alcon, C AU - Krouk, G AU - Benková, Eva AU - Nacry, P AU - Gojon, A AU - Bach, L ID - 7948 IS - 15 JF - Journal of Experimental Botany SN - 0022-0957 TI - The Arabidopsis NRT1.1 transceptor coordinately controls auxin biosynthesis and transport to regulate root branching in response to nitrate VL - 71 ER - TY - JOUR AB - 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]. AU - Yang, Yaping AU - Zhao, Gufang ID - 7940 JF - Transformation Groups SN - 10834362 TI - The PBW theorem for affine Yangians VL - 25 ER - TY - GEN AB - 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. AU - Hartstein, Mate AU - Hsu, Yu-Te AU - Modic, Kimberly A AU - Porras, Juan AU - Loew, Toshinao AU - Le Tacon, Matthieu AU - Zuo, Huakun AU - Wang, Jinhua AU - Zhu, Zengwei AU - Chan, Mun AU - McDonald, Ross AU - Lonzarich, Gilbert AU - Keimer, Bernhard AU - Sebastian, Suchitra AU - Harrison, Neil ID - 9708 TI - Accompanying dataset for 'Hard antinodal gap revealed by quantum oscillations in the pseudogap regime of underdoped high-Tc superconductors' ER - TY - CONF AB - 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. AU - Ashok, Pranav AU - Chatterjee, Krishnendu AU - Kretinsky, Jan AU - Weininger, Maximilian AU - Winkler, Tobias ID - 7955 SN - 9781450371049 T2 - Proceedings of the 35th Annual ACM/IEEE Symposium on Logic in Computer Science TI - Approximating values of generalized-reachability stochastic games ER - TY - JOUR AB - 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. AU - Parenti, Ilaria AU - Garcia Rabaneda, Luis E AU - Schön, Hanna AU - Novarino, Gaia ID - 7957 IS - 8 JF - Trends in Neurosciences SN - 01662236 TI - Neurodevelopmental disorders: From genetics to functional pathways VL - 43 ER - TY - JOUR AB - 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. AU - Kalai, Gil AU - Patakova, Zuzana ID - 7960 JF - Discrete and Computational Geometry SN - 01795376 TI - Intersection patterns of planar sets VL - 64 ER - TY - JOUR AB - 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. AU - Pach, János AU - Reed, Bruce AU - Yuditsky, Yelena ID - 7962 IS - 4 JF - Discrete and Computational Geometry SN - 01795376 TI - Almost all string graphs are intersection graphs of plane convex sets VL - 63 ER - TY - JOUR AB - 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. AU - Götberg, Ylva Louise Linsdotter AU - Korol, V. AU - Lamberts, A. AU - Kupfer, T. AU - Breivik, K. AU - Ludwig, B. AU - Drout, M. R. ID - 13460 IS - 1 JF - The Astrophysical Journal KW - Space and Planetary Science KW - Astronomy and Astrophysics SN - 0004-637X TI - Stars stripped in binaries: The living gravitational-wave sources VL - 904 ER - TY - JOUR AB - 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. AU - Trejo Banos, D AU - McCartney, DL AU - Patxot, M AU - Anchieri, L AU - Battram, T AU - Christiansen, C AU - Costeira, R AU - Walker, RM AU - Morris, SW AU - Campbell, A AU - Zhang, Q AU - Porteous, DJ AU - McRae, AF AU - Wray, NR AU - Visscher, PM AU - Haley, CS AU - Evans, KL AU - Deary, IJ AU - McIntosh, AM AU - Hemani, G AU - Bell, JT AU - Marioni, RE AU - Robinson, Matthew Richard ID - 7999 JF - Nature Communications SN - 2041-1723 TI - Bayesian reassessment of the epigenetic architecture of complex traits VL - 11 ER - TY - JOUR AB - 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. AU - Perini, Samuel AU - Rafajlović, Marina AU - Westram, Anja M AU - Johannesson, Kerstin AU - Butlin, Roger K. ID - 7995 IS - 7 JF - Evolution SN - 00143820 TI - Assortative mating, sexual selection, and their consequences for gene flow in Littorina VL - 74 ER - TY - GEN AB - 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. AU - Perini, Samuel AU - Rafajlovic, Marina AU - Westram, Anja M AU - Johannesson, Kerstin AU - Butlin, Roger ID - 8809 TI - Data from: Assortative mating, sexual selection and their consequences for gene flow in Littorina ER - TY - JOUR AB - 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. AU - Vandael, David H AU - Borges Merjane, Carolina AU - Zhang, Xiaomin AU - Jonas, Peter M ID - 8001 IS - 3 JF - Neuron SN - 0896-6273 TI - Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation VL - 107 ER - TY - JOUR AB - 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. AU - Vampa, Giulio AU - Lu, Jian AU - You, Yong Sing AU - Baykusheva, Denitsa Rangelova AU - Wu, Mengxi AU - Liu, Hanzhe AU - Schafer, Kenneth J AU - Gaarde, Mette B AU - Reis, David A AU - Ghimire, Shambhu ID - 13998 IS - 14 JF - Journal of Physics B: Atomic, Molecular and Optical Physics KW - Condensed Matter Physics KW - Atomic and Molecular Physics KW - and Optics SN - 0953-4075 TI - Attosecond synchronization of extreme ultraviolet high harmonics from crystals VL - 53 ER - TY - JOUR AB - 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. AU - Biswas, Shubhadeep AU - Förg, Benjamin AU - Ortmann, Lisa AU - Schötz, Johannes AU - Schweinberger, Wolfgang AU - Zimmermann, Tomáš AU - Pi, Liangwen AU - Baykusheva, Denitsa Rangelova AU - Masood, Hafiz A. AU - Liontos, Ioannis AU - Kamal, Amgad M. AU - Kling, Nora G. AU - Alharbi, Abdullah F. AU - Alharbi, Meshaal AU - Azzeer, Abdallah M. AU - Hartmann, Gregor AU - Wörner, Hans J. AU - Landsman, Alexandra S. AU - Kling, Matthias F. ID - 13999 IS - 7 JF - Nature Physics KW - General Physics and Astronomy SN - 1745-2473 TI - Probing molecular environment through photoemission delays VL - 16 ER - TY - JOUR AB - 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. AU - Fink, Johannes M AU - Kalaee, M. AU - Norte, R. AU - Pitanti, A. AU - Painter, O. ID - 8038 IS - 3 JF - Quantum Science and Technology TI - Efficient microwave frequency conversion mediated by a photonics compatible silicon nitride nanobeam oscillator VL - 5 ER - TY - JOUR AB - 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. AU - Lukacisinova, Marta AU - Fernando, Booshini AU - Bollenbach, Mark Tobias ID - 8037 JF - Nature Communications TI - Highly parallel lab evolution reveals that epistasis can curb the evolution of antibiotic resistance VL - 11 ER - TY - JOUR AB - 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. AU - Gupta, Chitrak AU - Khaniya, Umesh AU - Chan, Chun Kit AU - Dehez, Francois AU - Shekhar, Mrinal AU - Gunner, M. R. AU - Sazanov, Leonid A AU - Chipot, Christophe AU - Singharoy, Abhishek ID - 8040 IS - 20 JF - Journal of the American Chemical Society SN - 00027863 TI - Charge transfer and chemo-mechanical coupling in respiratory complex I VL - 142 ER - TY - JOUR AB - 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. AU - Collard, Ylona AU - Grosjean, Galien M AU - Vandewalle, Nicolas ID - 8036 JF - Communications Physics TI - Magnetically powered metachronal waves induce locomotion in self-assemblies VL - 3 ER - TY - JOUR AB - 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. AU - Paranjape, Chaitanya S AU - Duguet, Yohann AU - Hof, Björn ID - 8043 JF - Journal of Fluid Mechanics SN - 00221120 TI - Oblique stripe solutions of channel flow VL - 897 ER - TY - GEN AB - 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. AU - Gupta, Chitrak AU - Khaniya, Umesh AU - Chan, Chun AU - Dehez, Francois AU - Shekhar, Mrinal AU - Gunner, M. R. AU - Sazanov, Leonid A AU - Chipot, Christophe AU - Singharoy, Abhishek ID - 9326 TI - Charge transfer and chemo-mechanical coupling in respiratory complex I ER - TY - JOUR AB - 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. AU - Boccato, Chiara AU - Brennecke, Christian AU - Cenatiempo, Serena AU - Schlein, Benjamin ID - 8042 IS - 7 JF - Journal of the European Mathematical Society SN - 14359855 TI - The excitation spectrum of Bose gases interacting through singular potentials VL - 22 ER - TY - GEN AB - Additional analyses of the trajectories AU - Gupta, Chitrak AU - Khaniya, Umesh AU - Chan, Chun Kit AU - Dehez, Francois AU - Shekhar, Mrinal AU - Gunner, M.R. AU - Sazanov, Leonid A AU - Chipot, Christophe AU - Singharoy, Abhishek ID - 9713 TI - Supporting information ER - TY - GEN AU - Gupta, Chitrak AU - Khaniya, Umesh AU - Chan, Chun Kit AU - Dehez, Francois AU - Shekhar, Mrinal AU - Gunner, M.R. AU - Sazanov, Leonid A AU - Chipot, Christophe AU - Singharoy, Abhishek ID - 9878 TI - Movies ER - TY - JOUR AB - 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. AU - Hippe, Andreas AU - Braun, Stephan Alexander AU - Oláh, Péter AU - Gerber, Peter Arne AU - Schorr, Anne AU - Seeliger, Stephan AU - Holtz, Stephanie AU - Jannasch, Katharina AU - Pivarcsi, Andor AU - Buhren, Bettina AU - Schrumpf, Holger AU - Kislat, Andreas AU - Bünemann, Erich AU - Steinhoff, Martin AU - Fischer, Jens AU - Lira, Sérgio A. AU - Boukamp, Petra AU - Hevezi, Peter AU - Stoecklein, Nikolas Hendrik AU - Hoffmann, Thomas AU - Alves, Frauke AU - Sleeman, Jonathan AU - Bauer, Thomas AU - Klufa, Jörg AU - Amberg, Nicole AU - Sibilia, Maria AU - Zlotnik, Albert AU - Müller-Homey, Anja AU - Homey, Bernhard ID - 8093 JF - British Journal of Cancer SN - 0007-0920 TI - EGFR/Ras-induced CCL20 production modulates the tumour microenvironment VL - 123 ER - TY - JOUR AB - 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. AU - Seiringer, Robert AU - Yngvason, Jakob ID - 8091 JF - Journal of Statistical Physics SN - 00224715 TI - Emergence of Haldane pseudo-potentials in systems with short-range interactions VL - 181 ER - TY - JOUR AB - 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. AU - Shehu, Yekini AU - Iyiola, Olaniyi S. ID - 8077 JF - Applied Numerical Mathematics SN - 0168-9274 TI - Projection methods with alternating inertial steps for variational inequalities: Weak and linear convergence VL - 157 ER - TY - JOUR AB - 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. AU - Zhang, Yu AU - Liu, Yu AU - Xing, Congcong AU - Zhang, Ting AU - Li, Mengyao AU - Pacios, Mercè AU - Yu, Xiaoting AU - Arbiol, Jordi AU - Llorca, Jordi AU - Cadavid, Doris AU - Ibáñez, Maria AU - Cabot, Andreu ID - 8039 IS - 24 JF - ACS Applied Materials and Interfaces TI - Tin selenide molecular precursor for the solution processing of thermoelectric materials and devices VL - 12 ER - TY - JOUR AB - 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. AU - Hillary, Robert F. AU - Trejo-Banos, Daniel AU - Kousathanas, Athanasios AU - Mccartney, Daniel L. AU - Harris, Sarah E. AU - Stevenson, Anna J. AU - Patxot, Marion AU - Ojavee, Sven Erik AU - Zhang, Qian AU - Liewald, David C. AU - Ritchie, Craig W. AU - Evans, Kathryn L. AU - Tucker-Drob, Elliot M. AU - Wray, Naomi R. AU - Mcrae, Allan F. AU - Visscher, Peter M. AU - Deary, Ian J. AU - Robinson, Matthew Richard AU - Marioni, Riccardo E. ID - 8133 IS - 1 JF - Genome Medicine TI - Multi-method genome- and epigenome-wide studies of inflammatory protein levels in healthy older adults VL - 12 ER - TY - JOUR AB - 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. AU - Gonçalves, Pedro J. AU - Lueckmann, Jan-Matthis AU - Deistler, Michael AU - Nonnenmacher, Marcel AU - Öcal, Kaan AU - Bassetto, Giacomo AU - Chintaluri, Chaitanya AU - Podlaski, William F. AU - Haddad, Sara A. AU - Vogels, Tim P AU - Greenberg, David S. AU - Macke, Jakob H. ID - 8127 JF - eLife TI - Training deep neural density estimators to identify mechanistic models of neural dynamics VL - 9 ER - TY - JOUR AB - 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. AU - Agnes, Everton J. AU - Luppi, Andrea I. AU - Vogels, Tim P ID - 8126 IS - 50 JF - The Journal of Neuroscience TI - Complementary inhibitory weight profiles emerge from plasticity and allow attentional switching of receptive fields VL - 40 ER - TY - JOUR AB - 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. AU - Salzer, Elisabeth AU - Zoghi, Samaneh AU - Kiss, Máté G. AU - Kage, Frieda AU - Rashkova, Christina AU - Stahnke, Stephanie AU - Haimel, Matthias AU - Platzer, René AU - Caldera, Michael AU - Ardy, Rico Chandra AU - Hoeger, Birgit AU - Block, Jana AU - Medgyesi, David AU - Sin, Celine AU - Shahkarami, Sepideh AU - Kain, Renate AU - Ziaee, Vahid AU - Hammerl, Peter AU - Bock, Christoph AU - Menche, Jörg AU - Dupré, Loïc AU - Huppa, Johannes B. AU - Sixt, Michael K AU - Lomakin, Alexis AU - Rottner, Klemens AU - Binder, Christoph J. AU - Stradal, Theresia E.B. AU - Rezaei, Nima AU - Boztug, Kaan ID - 8132 IS - 49 JF - Science Immunology TI - The cytoskeletal regulator HEM1 governs B cell development and prevents autoimmunity VL - 5 ER - TY - GEN AB - 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). AU - Hillary, Robert F. AU - Trejo-Banos, Daniel AU - Kousathanas, Athanasios AU - McCartney, Daniel L. AU - Harris, Sarah E. AU - Stevenson, Anna J. AU - Patxot, Marion AU - Ojavee, Sven Erik AU - Zhang, Qian AU - Liewald, David C. AU - Ritchie, Craig W. AU - Evans, Kathryn L. AU - Tucker-Drob, Elliot M. AU - Wray, Naomi R. AU - McRae, Allan F. AU - Visscher, Peter M. AU - Deary, Ian J. AU - Robinson, Matthew Richard AU - Marioni, Riccardo E. ID - 9706 TI - Additional file 2 of multi-method genome- and epigenome-wide studies of inflammatory protein levels in healthy older adults ER - TY - JOUR AB - 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. AU - Mayer, Simon AU - Seiringer, Robert ID - 8134 IS - 6 JF - Journal of Mathematical Physics SN - 00222488 TI - The free energy of the two-dimensional dilute Bose gas. II. Upper bound VL - 61 ER - TY - JOUR AU - Barton, Nicholas H ID - 8112 IS - 1806 JF - Philosophical Transactions of the Royal Society. Series B: Biological Sciences SN - 0962-8436 TI - On the completion of speciation VL - 375 ER - TY - JOUR AB - 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. AU - Laukoter, Susanne AU - Pauler, Florian AU - Beattie, Robert J AU - Amberg, Nicole AU - Hansen, Andi H AU - Streicher, Carmen AU - Penz, Thomas AU - Bock, Christoph AU - Hippenmeyer, Simon ID - 8162 IS - 6 JF - Neuron SN - 0896-6273 TI - Cell-type specificity of genomic imprinting in cerebral cortex VL - 107 ER - TY - JOUR AB - Directional transport of the phytohormone auxin is a versatile, plant-specific mechanism regulating many aspects of plant development. The recently identified plant hormones, strigolactones (SLs), are implicated in many plant traits; among others, they modify the phenotypic output of PIN-FORMED (PIN) auxin transporters for fine-tuning of growth and developmental responses. Here, we show in pea and Arabidopsis that SLs target processes dependent on the canalization of auxin flow, which involves auxin feedback on PIN subcellular distribution. D14 receptor- and MAX2 F-box-mediated SL signaling inhibits the formation of auxin-conducting channels after wounding or from artificial auxin sources, during vasculature de novo formation and regeneration. At the cellular level, SLs interfere with auxin effects on PIN polar targeting, constitutive PIN trafficking as well as clathrin-mediated endocytosis. Our results identify a non-transcriptional mechanism of SL action, uncoupling auxin feedback on PIN polarity and trafficking, thereby regulating vascular tissue formation and regeneration. AU - Zhang, J AU - Mazur, E AU - Balla, J AU - Gallei, Michelle C AU - Kalousek, P AU - Medveďová, Z AU - Li, Y AU - Wang, Y AU - Prat, Tomas AU - Vasileva, Mina K AU - Reinöhl, V AU - Procházka, S AU - Halouzka, R AU - Tarkowski, P AU - Luschnig, C AU - Brewer, PB AU - Friml, Jiří ID - 8138 IS - 1 JF - Nature Communications SN - 2041-1723 TI - Strigolactones inhibit auxin feedback on PIN-dependent auxin transport canalization VL - 11 ER - TY - JOUR AB - Speciation, that is, the evolution of reproductive barriers eventually leading to complete isolation, is a crucial process generating biodiversity. Recent work has contributed much to our understanding of how reproductive barriers begin to evolve, and how they are maintained in the face of gene flow. However, little is known about the transition from partial to strong reproductive isolation (RI) and the completion of speciation. We argue that the evolution of strong RI is likely to involve different processes, or new interactions among processes, compared with the evolution of the first reproductive barriers. Transition to strong RI may be brought about by changing external conditions, for example, following secondary contact. However, the increasing levels of RI themselves create opportunities for new barriers to evolve and, and interaction or coupling among barriers. These changing processes may depend on genomic architecture and leave detectable signals in the genome. We outline outstanding questions and suggest more theoretical and empirical work, considering both patterns and processes associated with strong RI, is needed to understand how speciation is completed. AU - Kulmuni, Jonna AU - Butlin, Roger K. AU - Lucek, Kay AU - Savolainen, Vincent AU - Westram, Anja M ID - 8168 IS - 1806 JF - Philosophical Transactions of the Royal Society. Series B: Biological sciences SN - 0962-8436 TI - Towards the completion of speciation: The evolution of reproductive isolation beyond the first barriers VL - 375 ER - TY - JOUR AB - The evolution of strong reproductive isolation (RI) is fundamental to the origins and maintenance of biological diversity, especially in situations where geographical distributions of taxa broadly overlap. But what is the history behind strong barriers currently acting in sympatry? Using whole-genome sequencing and single nucleotide polymorphism genotyping, we inferred (i) the evolutionary relationships, (ii) the strength of RI, and (iii) the demographic history of divergence between two broadly sympatric taxa of intertidal snail. Despite being cryptic, based on external morphology, Littorina arcana and Littorina saxatilis differ in their mode of female reproduction (egg-laying versus brooding), which may generate a strong post-zygotic barrier. We show that egg-laying and brooding snails are closely related, but genetically distinct. Genotyping of 3092 snails from three locations failed to recover any recent hybrid or backcrossed individuals, confirming that RI is strong. There was, however, evidence for a very low level of asymmetrical introgression, suggesting that isolation remains incomplete. The presence of strong, asymmetrical RI was further supported by demographic analysis of these populations. Although the taxa are currently broadly sympatric, demographic modelling suggests that they initially diverged during a short period of geographical separation involving very low gene flow. Our study suggests that some geographical separation may kick-start the evolution of strong RI, facilitating subsequent coexistence of taxa in sympatry. The strength of RI needed to achieve sympatry and the subsequent effect of sympatry on RI remain open questions. AU - Stankowski, Sean AU - Westram, Anja M AU - Zagrodzka, Zuzanna B. AU - Eyres, Isobel AU - Broquet, Thomas AU - Johannesson, Kerstin AU - Butlin, Roger K. ID - 8167 IS - 1806 JF - Philosophical Transactions of the Royal Society. Series B: Biological Sciences TI - The evolution of strong reproductive isolation between sympatric intertidal snails VL - 375 ER - TY - JOUR AB - Alignment of OCS, CS2, and I2 molecules embedded in helium nanodroplets is measured as a function of time following rotational excitation by a nonresonant, comparatively weak ps laser pulse. The distinct peaks in the power spectra, obtained by Fourier analysis, are used to determine the rotational, B, and centrifugal distortion, D, constants. For OCS, B and D match the values known from IR spectroscopy. For CS2 and I2, they are the first experimental results reported. The alignment dynamics calculated from the gas-phase rotational Schrödinger equation, using the experimental in-droplet B and D values, agree in detail with the measurement for all three molecules. The rotational spectroscopy technique for molecules in helium droplets introduced here should apply to a range of molecules and complexes. AU - Chatterley, Adam S. AU - Christiansen, Lars AU - Schouder, Constant A. AU - Jørgensen, Anders V. AU - Shepperson, Benjamin AU - Cherepanov, Igor AU - Bighin, Giacomo AU - Zillich, Robert E. AU - Lemeshko, Mikhail AU - Stapelfeldt, Henrik ID - 8170 IS - 1 JF - Physical Review Letters SN - 00319007 TI - Rotational coherence spectroscopy of molecules in Helium nanodroplets: Reconciling the time and the frequency domains VL - 125 ER - TY - CONF AB - Fixed-point arithmetic is a popular alternative to floating-point arithmetic on embedded systems. Existing work on the verification of fixed-point programs relies on custom formalizations of fixed-point arithmetic, which makes it hard to compare the described techniques or reuse the implementations. In this paper, we address this issue by proposing and formalizing an SMT theory of fixed-point arithmetic. We present an intuitive yet comprehensive syntax of the fixed-point theory, and provide formal semantics for it based on rational arithmetic. We also describe two decision procedures for this theory: one based on the theory of bit-vectors and the other on the theory of reals. We implement the two decision procedures, and evaluate our implementations using existing mature SMT solvers on a benchmark suite we created. Finally, we perform a case study of using the theory we propose to verify properties of quantized neural networks. AU - Baranowski, Marek AU - He, Shaobo AU - Lechner, Mathias AU - Nguyen, Thanh Son AU - Rakamarić, Zvonimir ID - 8194 SN - 03029743 T2 - Automated Reasoning TI - An SMT theory of fixed-point arithmetic VL - 12166 ER - TY - JOUR AB - Many recent studies have addressed the mechanisms operating during the early stages of speciation, but surprisingly few studies have tested theoretical predictions on the evolution of strong reproductive isolation (RI). To help address this gap, we first undertook a quantitative review of the hybrid zone literature for flowering plants in relation to reproductive barriers. Then, using Populus as an exemplary model group, we analysed genome-wide variation for phylogenetic tree topologies in both early- and late-stage speciation taxa to determine how these patterns may be related to the genomic architecture of RI. Our plant literature survey revealed variation in barrier complexity and an association between barrier number and introgressive gene flow. Focusing on Populus, our genome-wide analysis of tree topologies in speciating poplar taxa points to unusually complex genomic architectures of RI, consistent with earlier genome-wide association studies. These architectures appear to facilitate the ‘escape’ of introgressed genome segments from polygenic barriers even with strong RI, thus affecting their relationships with recombination rates. Placed within the context of the broader literature, our data illustrate how phylogenomic approaches hold great promise for addressing the evolution and temporary breakdown of RI during late stages of speciation. AU - Shang, Huiying AU - Hess, Jaqueline AU - Pickup, Melinda AU - Field, David AU - Ingvarsson, Pär K. AU - Liu, Jianquan AU - Lexer, Christian ID - 8169 IS - 1806 JF - Philosophical Transactions of the Royal Society. Series B: Biological Sciences TI - Evolution of strong reproductive isolation in plants: Broad-scale patterns and lessons from a perennial model group VL - 375 ER - TY - JOUR AB - Direct ethanol fuel cells (DEFCs) show a huge potential to power future electric vehicles and portable electronics, but their deployment is currently limited by the unavailability of proper electrocatalysis for the ethanol oxidation reaction (EOR). In this work, we engineer a new electrocatalyst by incorporating phosphorous into a palladium-tin alloy and demonstrate a significant performance improvement toward EOR. We first detail a synthetic method to produce Pd2Sn:P nanocrystals that incorporate 35% of phosphorus. These nanoparticles are supported on carbon black and tested for EOR. Pd2Sn:P/C catalysts exhibit mass current densities up to 5.03 A mgPd−1, well above those of Pd2Sn/C, PdP2/C and Pd/C reference catalysts. Furthermore, a twofold lower Tafel slope and a much longer durability are revealed for the Pd2Sn:P/C catalyst compared with Pd/C. The performance improvement is rationalized with the aid of density functional theory (DFT) calculations considering different phosphorous chemical environments. Depending on its oxidation state, surface phosphorus introduces sites with low energy OH− adsorption and/or strongly influences the electronic structure of palladium and tin to facilitate the oxidation of the acetyl to acetic acid, which is considered the EOR rate limiting step. DFT calculations also points out that the durability improvement of Pd2Sn:P/C catalyst is associated to the promotion of OH adsorption that accelerates the oxidation of intermediate poisoning COads, reactivating the catalyst surface. AU - Yu, Xiaoting AU - Liu, Junfeng AU - Li, Junshan AU - Luo, Zhishan AU - Zuo, Yong AU - Xing, Congcong AU - Llorca, Jordi AU - Nasiou, Déspina AU - Arbiol, Jordi AU - Pan, Kai AU - Kleinhanns, Tobias AU - Xie, Ying AU - Cabot, Andreu ID - 8189 IS - 11 JF - Nano Energy SN - 2211-2855 TI - Phosphorous incorporation in Pd2Sn alloys for electrocatalytic ethanol oxidation VL - 77 ER - TY - JOUR AB - Understanding to what extent stem cell potential is a cell-intrinsic property or an emergent behavior coming from global tissue dynamics and geometry is a key outstanding question of systems and stem cell biology. Here, we propose a theory of stem cell dynamics as a stochastic competition for access to a spatially localized niche, giving rise to a stochastic conveyor-belt model. Cell divisions produce a steady cellular stream which advects cells away from the niche, while random rearrangements enable cells away from the niche to be favorably repositioned. Importantly, even when assuming that all cells in a tissue are molecularly equivalent, we predict a common (“universal”) functional dependence of the long-term clonal survival probability on distance from the niche, as well as the emergence of a well-defined number of functional stem cells, dependent only on the rate of random movements vs. mitosis-driven advection. We test the predictions of this theory on datasets of pubertal mammary gland tips and embryonic kidney tips, as well as homeostatic intestinal crypts. Importantly, we find good agreement for the predicted functional dependency of the competition as a function of position, and thus functional stem cell number in each organ. This argues for a key role of positional fluctuations in dictating stem cell number and dynamics, and we discuss the applicability of this theory to other settings. AU - Corominas-Murtra, Bernat AU - Scheele, Colinda L.G.J. AU - Kishi, Kasumi AU - Ellenbroek, Saskia I.J. AU - Simons, Benjamin D. AU - Van Rheenen, Jacco AU - Hannezo, Edouard B ID - 8220 IS - 29 JF - Proceedings of the National Academy of Sciences of the United States of America TI - Stem cell lineage survival as a noisy competition for niche access VL - 117 ER - TY - JOUR AB - We investigate a mechanism to transiently stabilize topological phenomena in long-lived quasi-steady states of isolated quantum many-body systems driven at low frequencies. We obtain an analytical bound for the lifetime of the quasi-steady states which is exponentially large in the inverse driving frequency. Within this lifetime, the quasi-steady state is characterized by maximum entropy subject to the constraint of fixed number of particles in the system's Floquet-Bloch bands. In such a state, all the non-universal properties of these bands are washed out, hence only the topological properties persist. AU - Gulden, Tobias AU - Berg, Erez AU - Rudner, Mark Spencer AU - Lindner, Netanel ID - 8199 JF - SciPost Physics SN - 2542-4653 TI - Exponentially long lifetime of universal quasi-steady states in topological Floquet pumps VL - 9 ER - TY - JOUR AB - Dentate gyrus granule cells (GCs) connect the entorhinal cortex to the hippocampal CA3 region, but how they process spatial information remains enigmatic. To examine the role of GCs in spatial coding, we measured excitatory postsynaptic potentials (EPSPs) and action potentials (APs) in head-fixed mice running on a linear belt. Intracellular recording from morphologically identified GCs revealed that most cells were active, but activity level varied over a wide range. Whereas only ∼5% of GCs showed spatially tuned spiking, ∼50% received spatially tuned input. Thus, the GC population broadly encodes spatial information, but only a subset relays this information to the CA3 network. Fourier analysis indicated that GCs received conjunctive place-grid-like synaptic input, suggesting code conversion in single neurons. GC firing was correlated with dendritic complexity and intrinsic excitability, but not extrinsic excitatory input or dendritic cable properties. Thus, functional maturation may control input-output transformation and spatial code conversion. AU - Zhang, Xiaomin AU - Schlögl, Alois AU - Jonas, Peter M ID - 8261 IS - 6 JF - Neuron SN - 0896-6273 TI - Selective routing of spatial information flow from input to output in hippocampal granule cells VL - 107 ER - TY - JOUR AB - Modern scientific instruments produce vast amounts of data, which can overwhelm the processing ability of computer systems. Lossy compression of data is an intriguing solution, but comes with its own drawbacks, such as potential signal loss, and the need for careful optimization of the compression ratio. In this work, we focus on a setting where this problem is especially acute: compressive sensing frameworks for interferometry and medical imaging. We ask the following question: can the precision of the data representation be lowered for all inputs, with recovery guarantees and practical performance Our first contribution is a theoretical analysis of the normalized Iterative Hard Thresholding (IHT) algorithm when all input data, meaning both the measurement matrix and the observation vector are quantized aggressively. We present a variant of low precision normalized IHT that, under mild conditions, can still provide recovery guarantees. The second contribution is the application of our quantization framework to radio astronomy and magnetic resonance imaging. We show that lowering the precision of the data can significantly accelerate image recovery. We evaluate our approach on telescope data and samples of brain images using CPU and FPGA implementations achieving up to a 9x speedup with negligible loss of recovery quality. AU - Gurel, Nezihe Merve AU - Kara, Kaan AU - Stojanov, Alen AU - Smith, Tyler AU - Lemmin, Thomas AU - Alistarh, Dan-Adrian AU - Puschel, Markus AU - Zhang, Ce ID - 8268 JF - IEEE Transactions on Signal Processing SN - 1053587X TI - Compressive sensing using iterative hard thresholding with low precision data representation: Theory and applications VL - 68 ER - TY - JOUR AU - He, Peng AU - Zhang, Yuzhou AU - Xiao, Guanghui ID - 8271 IS - 9 JF - Molecular Plant SN - 16742052 TI - Origin of a subgenome and genome evolution of allotetraploid cotton species VL - 13 ER - TY - JOUR AB - By rigorously accounting for mesoscale spatial correlations in donor/acceptor surface properties, we develop a scale-spanning model for same-material tribocharging. We find that mesoscale correlations affect not only the magnitude of charge transfer but also the fluctuations—suppressing otherwise overwhelming charge-transfer variability that is not observed experimentally. We furthermore propose a generic theoretical mechanism by which the mesoscale features might emerge, which is qualitatively consistent with other proposals in the literature. AU - Grosjean, Galien M AU - Wald, Sebastian AU - Sobarzo Ponce, Juan Carlos A AU - Waitukaitis, Scott R ID - 8101 IS - 8 JF - Physical Review Materials KW - electric charge KW - tribocharging KW - soft matter KW - granular materials KW - polymers SN - 2475-9953 TI - Quantitatively consistent scale-spanning model for same-material tribocharging VL - 4 ER - TY - JOUR AB - Let 𝐹:ℤ2→ℤ be the pointwise minimum of several linear functions. The theory of smoothing allows us to prove that under certain conditions there exists the pointwise minimal function among all integer-valued superharmonic functions coinciding with F “at infinity”. We develop such a theory to prove existence of so-called solitons (or strings) in a sandpile model, studied by S. Caracciolo, G. Paoletti, and A. Sportiello. Thus we made a step towards understanding the phenomena of the identity in the sandpile group for planar domains where solitons appear according to experiments. We prove that sandpile states, defined using our smoothing procedure, move changeless when we apply the wave operator (that is why we call them solitons), and can interact, forming triads and nodes. AU - Kalinin, Nikita AU - Shkolnikov, Mikhail ID - 8325 IS - 9 JF - Communications in Mathematical Physics SN - 00103616 TI - Sandpile solitons via smoothing of superharmonic functions VL - 378 ER - TY - JOUR AB - Complex I is the first and the largest enzyme of respiratory chains in bacteria and mitochondria. The mechanism which couples spatially separated transfer of electrons to proton translocation in complex I is not known. Here we report five crystal structures of T. thermophilus enzyme in complex with NADH or quinone-like compounds. We also determined cryo-EM structures of major and minor native states of the complex, differing in the position of the peripheral arm. Crystal structures show that binding of quinone-like compounds (but not of NADH) leads to a related global conformational change, accompanied by local re-arrangements propagating from the quinone site to the nearest proton channel. Normal mode and molecular dynamics analyses indicate that these are likely to represent the first steps in the proton translocation mechanism. Our results suggest that quinone binding and chemistry play a key role in the coupling mechanism of complex I. AU - Gutierrez-Fernandez, Javier AU - Kaszuba, Karol AU - Minhas, Gurdeep S. AU - Baradaran, Rozbeh AU - Tambalo, Margherita AU - Gallagher, David T. AU - Sazanov, Leonid A ID - 8318 IS - 1 JF - Nature Communications TI - Key role of quinone in the mechanism of respiratory complex I VL - 11 ER - TY - JOUR AB - The genetic code is considered to use five nucleic bases (adenine, guanine, cytosine, thymine and uracil), which form two pairs for encoding information in DNA and two pairs for encoding information in RNA. Nevertheless, in recent years several artificial base pairs have been developed in attempts to expand the genetic code. Employment of these additional base pairs increases the information capacity and variety of DNA sequences, and provides a platform for the site-specific, enzymatic incorporation of extra functional components into DNA and RNA. As a result, of the development of such expanded systems, many artificial base pairs have been synthesized and tested under various conditions. Following many stages of enhancement, unnatural base pairs have been modified to eliminate their weak points, qualifying them for specific research needs. Moreover, the first attempts to create a semi-synthetic organism containing DNA with unnatural base pairs seem to have been successful. This further extends the possible applications of these kinds of pairs. Herein, we describe the most significant qualities of unnatural base pairs and their actual applications. AU - Mukba, S. A. AU - Vlasov, Petr AU - Kolosov, P. M. AU - Shuvalova, E. Y. AU - Egorova, T. V. AU - Alkalaeva, E. Z. ID - 8320 IS - 4 JF - Molecular Biology SN - 00268933 TI - Expanding the genetic code: Unnatural base pairs in biological systems VL - 54 ER - TY - JOUR AB - The genetic code is considered to use five nucleic bases (adenine, guanine, cytosine, thymine and uracil), which form two pairs for encoding information in DNA and two pairs for encoding information in RNA. Nevertheless, in recent years several artificial base pairs have been developed in attempts to expand the genetic code. Employment of these additional base pairs increases the information capacity and variety of DNA sequences, and provides a platform for the site-specific, enzymatic incorporation of extra functional components into DNA and RNA. As a result, of the development of such expanded systems, many artificial base pairs have been synthesized and tested under various conditions. Following many stages of enhancement, unnatural base pairs have been modified to eliminate their weak points, qualifying them for specific research needs. Moreover, the first attempts to create a semi-synthetic organism containing DNA with unnatural base pairs seem to have been successful. This further extends the possible applications of these kinds of pairs. Herein, we describe the most significant qualities of unnatural base pairs and their actual applications. AU - Mukba, S. A. AU - Vlasov, Petr AU - Kolosov, P. M. AU - Shuvalova, E. Y. AU - Egorova, T. V. AU - Alkalaeva, E. Z. ID - 8321 IS - 4 JF - Molekuliarnaia biologiia SN - 00268984 TI - Expanding the genetic code: Unnatural base pairs in biological systems VL - 54 ER - TY - JOUR AU - Pach, János ID - 8323 JF - Discrete and Computational Geometry SN - 01795376 TI - A farewell to Ricky Pollack VL - 64 ER - TY - JOUR AB - Plant hormone cytokinins are perceived by a subfamily of sensor histidine kinases (HKs), which via a two-component phosphorelay cascade activate transcriptional responses in the nucleus. Subcellular localization of the receptors proposed the endoplasmic reticulum (ER) membrane as a principal cytokinin perception site, while study of cytokinin transport pointed to the plasma membrane (PM)-mediated cytokinin signalling. Here, by detailed monitoring of subcellular localizations of the fluorescently labelled natural cytokinin probe and the receptor ARABIDOPSIS HISTIDINE KINASE 4 (CRE1/AHK4) fused to GFP reporter, we show that pools of the ER-located cytokinin receptors can enter the secretory pathway and reach the PM in cells of the root apical meristem, and the cell plate of dividing meristematic cells. Brefeldin A (BFA) experiments revealed vesicular recycling of the receptor and its accumulation in BFA compartments. We provide a revised view on cytokinin signalling and the possibility of multiple sites of perception at PM and ER. AU - Kubiasova, Karolina AU - Montesinos López, Juan C AU - Šamajová, Olga AU - Nisler, Jaroslav AU - Mik, Václav AU - Semeradova, Hana AU - Plíhalová, Lucie AU - Novák, Ondřej AU - Marhavý, Peter AU - Cavallari, Nicola AU - Zalabák, David AU - Berka, Karel AU - Doležal, Karel AU - Galuszka, Petr AU - Šamaj, Jozef AU - Strnad, Miroslav AU - Benková, Eva AU - Plíhal, Ondřej AU - Spíchal, Lukáš ID - 8336 JF - Nature Communications TI - Cytokinin fluoroprobe reveals multiple sites of cytokinin perception at plasma membrane and endoplasmic reticulum VL - 11 ER - TY - JOUR AB - Cytokinins are mobile multifunctional plant hormones with roles in development and stress resilience. Although their Histidine Kinase receptors are substantially localised to the endoplasmic reticulum, cellular sites of cytokinin perception and importance of spatially heterogeneous cytokinin distribution continue to be debated. Here we show that cytokinin perception by plasma membrane receptors is an effective additional path for cytokinin response. Readout from a Two Component Signalling cytokinin-specific reporter (TCSn::GFP) closely matches intracellular cytokinin content in roots, yet we also find cytokinins in extracellular fluid, potentially enabling action at the cell surface. Cytokinins covalently linked to beads that could not pass the plasma membrane increased expression of both TCSn::GFP and Cytokinin Response Factors. Super-resolution microscopy of GFP-labelled receptors and diminished TCSn::GFP response to immobilised cytokinins in cytokinin receptor mutants, further indicate that receptors can function at the cell surface. We argue that dual intracellular and surface locations may augment flexibility of cytokinin responses. AU - Antoniadi, Ioanna AU - Novák, Ondřej AU - Gelová, Zuzana AU - Johnson, Alexander J AU - Plíhal, Ondřej AU - Simerský, Radim AU - Mik, Václav AU - Vain, Thomas AU - Mateo-Bonmatí, Eduardo AU - Karady, Michal AU - Pernisová, Markéta AU - Plačková, Lenka AU - Opassathian, Korawit AU - Hejátko, Jan AU - Robert, Stéphanie AU - Friml, Jiří AU - Doležal, Karel AU - Ljung, Karin AU - Turnbull, Colin ID - 8337 JF - Nature Communications TI - Cell-surface receptors enable perception of extracellular cytokinins VL - 11 ER - TY - GEN AB - With the lithium-ion technology approaching its intrinsic limit with graphite-based anodes, lithium metal is recently receiving renewed interest from the battery community as potential high capacity anode for next-generation rechargeable batteries. In this focus paper, we review the main advances in this field since the first attempts in the mid-1970s. Strategies for enabling reversible cycling and avoiding dendrite growth are thoroughly discussed, including specific applications in all-solid-state (polymeric and inorganic), Lithium-sulphur and Li-O2 (air) batteries. A particular attention is paid to review recent developments in regard of prototype manufacturing and current state-ofthe-art of these battery technologies with respect to the 2030 targets of the EU Integrated Strategic Energy Technology Plan (SET-Plan) Action 7. AU - Varzi, Alberto AU - Thanner, Katharina AU - Scipioni, Roberto AU - Di Lecce, Daniele AU - Hassoun, Jusef AU - Dörfler, Susanne AU - Altheus, Holger AU - Kaskel, Stefan AU - Prehal, Christian AU - Freunberger, Stefan Alexander ID - 8067 KW - Battery KW - Lithium metal KW - Lithium-sulphur KW - Lithium-air KW - All-solid-state SN - 2664-1690 TI - Current status and future perspectives of Lithium metal batteries ER - TY - JOUR AB - With the lithium-ion technology approaching its intrinsic limit with graphite-based anodes, Li metal is recently receiving renewed interest from the battery community as potential high capacity anode for next-generation rechargeable batteries. In this focus paper, we review the main advances in this field since the first attempts in the mid-1970s. Strategies for enabling reversible cycling and avoiding dendrite growth are thoroughly discussed, including specific applications in all-solid-state (inorganic and polymeric), Lithium–Sulfur (Li–S) and Lithium-O2 (air) batteries. A particular attention is paid to recent developments of these battery technologies and their current state with respect to the 2030 targets of the EU Integrated Strategic Energy Technology Plan (SET-Plan) Action 7. AU - Varzi, Alberto AU - Thanner, Katharina AU - Scipioni, Roberto AU - Di Lecce, Daniele AU - Hassoun, Jusef AU - Dörfler, Susanne AU - Altheus, Holger AU - Kaskel, Stefan AU - Prehal, Christian AU - Freunberger, Stefan Alexander ID - 8361 IS - 12 JF - Journal of Power Sources SN - 0378-7753 TI - Current status and future perspectives of lithium metal batteries VL - 480 ER - TY - GEN AB - The present review addresses the technical advances and the theoretical developments to realize and rationalize attosecond-science experiments that reveal a new dynamical time scale (10−15-10−18 s), with a particular emphasis on molecular systems and the implications of attosecond processes for chemical dynamics. After a brief outline of the theoretical framework for treating non-perturbative phenomena in Section 2, we introduce the physical mechanisms underlying high-harmonic generation and attosecond technology. The relevant technological developments and experimental schemes are covered in Section 3. Throughout the remainder of the chapter, we report on selected applications in molecular attosecond physics, thereby addressing specific phenomena mediated by purely electronic dynamics: charge localization in molecular hydrogen, charge migration in biorelevant molecules, high-harmonic spectroscopy, and delays in molecular photoionization. AU - Baykusheva, Denitsa Rangelova AU - Wörner, Hans Jakob ID - 14028 TI - Attosecond molecular spectroscopy and dynamics ER - TY - JOUR AB - Practical quantum networks require low-loss and noise-resilient optical interconnects as well as non-Gaussian resources for entanglement distillation and distributed quantum computation. The latter could be provided by superconducting circuits but existing solutions to interface the microwave and optical domains lack either scalability or efficiency, and in most cases the conversion noise is not known. In this work we utilize the unique opportunities of silicon photonics, cavity optomechanics and superconducting circuits to demonstrate a fully integrated, coherent transducer interfacing the microwave X and the telecom S bands with a total (internal) bidirectional transduction efficiency of 1.2% (135%) at millikelvin temperatures. The coupling relies solely on the radiation pressure interaction mediated by the femtometer-scale motion of two silicon nanobeams reaching a Vπ as low as 16 μV for sub-nanowatt pump powers. Without the associated optomechanical gain, we achieve a total (internal) pure conversion efficiency of up to 0.019% (1.6%), relevant for future noise-free operation on this qubit-compatible platform. AU - Arnold, Georg M AU - Wulf, Matthias AU - Barzanjeh, Shabir AU - Redchenko, Elena AU - Rueda Sanchez, Alfredo R AU - Hease, William J AU - Hassani, Farid AU - Fink, Johannes M ID - 8529 JF - Nature Communications KW - General Biochemistry KW - Genetics and Molecular Biology KW - General Physics and Astronomy KW - General Chemistry SN - 2041-1723 TI - Converting microwave and telecom photons with a silicon photonic nanomechanical interface VL - 11 ER - TY - JOUR AB - We propose a method to enhance the visual detail of a water surface simulation. Our method works as a post-processing step which takes a simulation as input and increases its apparent resolution by simulating many detailed Lagrangian water waves on top of it. We extend linear water wave theory to work in non-planar domains which deform over time, and we discretize the theory using Lagrangian wave packets attached to spline curves. The method is numerically stable and trivially parallelizable, and it produces high frequency ripples with dispersive wave-like behaviors customized to the underlying fluid simulation. AU - Skrivan, Tomas AU - Soderstrom, Andreas AU - Johansson, John AU - Sprenger, Christoph AU - Museth, Ken AU - Wojtan, Christopher J ID - 8535 IS - 4 JF - ACM Transactions on Graphics SN - 07300301 TI - Wave curves: Simulating Lagrangian water waves on dynamically deforming surfaces VL - 39 ER - TY - JOUR AB - Cohomological and K-theoretic stable bases originated from the study of quantum cohomology and quantum K-theory. Restriction formula for cohomological stable bases played an important role in computing the quantum connection of cotangent bundle of partial flag varieties. In this paper we study the K-theoretic stable bases of cotangent bundles of flag varieties. We describe these bases in terms of the action of the affine Hecke algebra and the twisted group algebra of KostantKumar. Using this algebraic description and the method of root polynomials, we give a restriction formula of the stable bases. We apply it to obtain the restriction formula for partial flag varieties. We also build a relation between the stable basis and the Casselman basis in the principal series representations of the Langlands dual group. As an application, we give a closed formula for the transition matrix between Casselman basis and the characteristic functions. AU - Su, C. AU - Zhao, Gufang AU - Zhong, C. ID - 8539 IS - 3 JF - Annales Scientifiques de l'Ecole Normale Superieure SN - 0012-9593 TI - On the K-theory stable bases of the springer resolution VL - 53 ER - TY - CHAP AB - This chapter presents an overview of the state of the art in attosecond time-resolved spectroscopy. The theoretical foundations of strong-field light–matter interaction and attosecond pulse generation are described. The enabling laser technologies are reviewed from chirped-pulse amplification and carrier-envelope-phase stabilization to the generation and characterization of attosecond pulses. The applications of attosecond pulses and pulse trains in electron- or ion-imaging experiments are presented, followed by attosecond electron spectroscopy in larger molecules. After this, high-harmonic spectroscopy and its applications to probing charge migration on attosecond time scales is reviewed. The rapidly evolving field of molecular photoionization delays is discussed. Finally, the applications of attosecond transient absorption to probing molecular dynamics are presented. AU - Baykusheva, Denitsa Rangelova AU - Wörner, Hans Jakob ED - Marquardt, Roberto ED - Quack, Martin ID - 14000 SN - 9780128172353 T2 - Molecular Spectroscopy and Quantum Dynamics TI - Attosecond Molecular Dynamics and Spectroscopy ER - TY - GEN AB - This datasets comprises all data shown in plots of the submitted article "Converting microwave and telecom photons with a silicon photonic nanomechanical interface". Additional raw data are available from the corresponding author on reasonable request. AU - Arnold, Georg M AU - Wulf, Matthias AU - Barzanjeh, Shabir AU - Redchenko, Elena AU - Rueda Sanchez, Alfredo R AU - Hease, William J AU - Hassani, Farid AU - Fink, Johannes M ID - 13056 TI - Converting microwave and telecom photons with a silicon photonic nanomechanical interface ER - TY - JOUR AB - Copper (Cu) is an essential trace element for all living organisms and used as cofactor in key enzymes of important biological processes, such as aerobic respiration or superoxide dismutation. However, due to its toxicity, cells have developed elaborate mechanisms for Cu homeostasis, which balance Cu supply for cuproprotein biogenesis with the need to remove excess Cu. This review summarizes our current knowledge on bacterial Cu homeostasis with a focus on Gram-negative bacteria and describes the multiple strategies that bacteria use for uptake, storage and export of Cu. We furthermore describe general mechanistic principles that aid the bacterial response to toxic Cu concentrations and illustrate dedicated Cu relay systems that facilitate Cu delivery for cuproenzyme biogenesis. Progress in understanding how bacteria avoid Cu poisoning while maintaining a certain Cu quota for cell proliferation is of particular importance for microbial pathogens because Cu is utilized by the host immune system for attenuating pathogen survival in host cells. AU - Andrei, Andreea AU - Öztürk, Yavuz AU - Khalfaoui-Hassani, Bahia AU - Rauch, Juna AU - Marckmann, Dorian AU - Trasnea, Petru Iulian AU - Daldal, Fevzi AU - Koch, Hans-Georg ID - 8579 IS - 9 JF - Membranes TI - Cu homeostasis in bacteria: The ins and outs VL - 10 ER - TY - JOUR AB - The majority of adenosine triphosphate (ATP) powering cellular processes in eukaryotes is produced by the mitochondrial F1Fo ATP synthase. Here, we present the atomic models of the membrane Fo domain and the entire mammalian (ovine) F1Fo, determined by cryo-electron microscopy. Subunits in the membrane domain are arranged in the ‘proton translocation cluster’ attached to the c-ring and a more distant ‘hook apparatus’ holding subunit e. Unexpectedly, this subunit is anchored to a lipid ‘plug’ capping the c-ring. We present a detailed proton translocation pathway in mammalian Fo and key inter-monomer contacts in F1Fo multimers. Cryo-EM maps of F1Fo exposed to calcium reveal a retracted subunit e and a disassembled c-ring, suggesting permeability transition pore opening. We propose a model for the permeability transition pore opening, whereby subunit e pulls the lipid plug out of the c-ring. Our structure will allow the design of drugs for many emerging applications in medicine. AU - Pinke, Gergely AU - Zhou, Long AU - Sazanov, Leonid A ID - 8581 IS - 11 JF - Nature Structural and Molecular Biology SN - 15459993 TI - Cryo-EM structure of the entire mammalian F-type ATP synthase VL - 27 ER - TY - CONF AB - We evaluate the usefulness of persistent homology in the analysis of heart rate variability. In our approach we extract several topological descriptors characterising datasets of RR-intervals, which are later used in classical machine learning algorithms. By this method we are able to differentiate the group of patients with the history of transient ischemic attack and the group of hypertensive patients. AU - Graff, Grzegorz AU - Graff, Beata AU - Jablonski, Grzegorz AU - Narkiewicz, Krzysztof ID - 8580 SN - 9781728157511 T2 - 11th Conference of the European Study Group on Cardiovascular Oscillations: Computation and Modelling in Physiology: New Challenges and Opportunities, TI - The application of persistent homology in the analysis of heart rate variability ER - TY - JOUR AB - Glioblastoma is the most malignant cancer in the brain and currently incurable. It is urgent to identify effective targets for this lethal disease. Inhibition of such targets should suppress the growth of cancer cells and, ideally also precancerous cells for early prevention, but minimally affect their normal counterparts. Using genetic mouse models with neural stem cells (NSCs) or oligodendrocyte precursor cells (OPCs) as the cells‐of‐origin/mutation, it is shown that the susceptibility of cells within the development hierarchy of glioma to the knockout of insulin‐like growth factor I receptor (IGF1R) is determined not only by their oncogenic states, but also by their cell identities/states. Knockout of IGF1R selectively disrupts the growth of mutant and transformed, but not normal OPCs, or NSCs. The desirable outcome of IGF1R knockout on cell growth requires the mutant cells to commit to the OPC identity regardless of its development hierarchical status. At the molecular level, oncogenic mutations reprogram the cellular network of OPCs and force them to depend more on IGF1R for their growth. A new‐generation brain‐penetrable, orally available IGF1R inhibitor harnessing tumor OPCs in the brain is also developed. The findings reveal the cellular window of IGF1R targeting and establish IGF1R as an effective target for the prevention and treatment of glioblastoma. AU - Tian, Anhao AU - Kang, Bo AU - Li, Baizhou AU - Qiu, Biying AU - Jiang, Wenhong AU - Shao, Fangjie AU - Gao, Qingqing AU - Liu, Rui AU - Cai, Chengwei AU - Jing, Rui AU - Wang, Wei AU - Chen, Pengxiang AU - Liang, Qinghui AU - Bao, Lili AU - Man, Jianghong AU - Wang, Yan AU - Shi, Yu AU - Li, Jin AU - Yang, Minmin AU - Wang, Lisha AU - Zhang, Jianmin AU - Hippenmeyer, Simon AU - Zhu, Junming AU - Bian, Xiuwu AU - Wang, Ying‐Jie AU - Liu, Chong ID - 8592 IS - 21 JF - Advanced Science KW - General Engineering KW - General Physics and Astronomy KW - General Materials Science KW - Medicine (miscellaneous) KW - General Chemical Engineering KW - Biochemistry KW - Genetics and Molecular Biology (miscellaneous) SN - 2198-3844 TI - Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting VL - 7 ER - TY - JOUR AB - Aqueous iodine based electrochemical energy storage is considered a potential candidate to improve sustainability and performance of current battery and supercapacitor technology. It harnesses the redox activity of iodide, iodine, and polyiodide species in the confined geometry of nanoporous carbon electrodes. However, current descriptions of the electrochemical reaction mechanism to interconvert these species are elusive. Here we show that electrochemical oxidation of iodide in nanoporous carbons forms persistent solid iodine deposits. Confinement slows down dissolution into triiodide and pentaiodide, responsible for otherwise significant self-discharge via shuttling. The main tools for these insights are in situ Raman spectroscopy and in situ small and wide-angle X-ray scattering (in situ SAXS/WAXS). In situ Raman confirms the reversible formation of triiodide and pentaiodide. In situ SAXS/WAXS indicates remarkable amounts of solid iodine deposited in the carbon nanopores. Combined with stochastic modeling, in situ SAXS allows quantifying the solid iodine volume fraction and visualizing the iodine structure on 3D lattice models at the sub-nanometer scale. Based on the derived mechanism, we demonstrate strategies for improved iodine pore filling capacity and prevention of self-discharge, applicable to hybrid supercapacitors and batteries. AU - Prehal, Christian AU - Fitzek, Harald AU - Kothleitner, Gerald AU - Presser, Volker AU - Gollas, Bernhard AU - Freunberger, Stefan Alexander AU - Abbas, Qamar ID - 8568 JF - Nature Communications KW - General Biochemistry KW - Genetics and Molecular Biology KW - General Physics and Astronomy KW - General Chemistry SN - 2041-1723 TI - Persistent and reversible solid iodine electrodeposition in nanoporous carbons VL - 11 ER - TY - JOUR AB - The parabigeminal nucleus (PBG) is the mammalian homologue to the isthmic complex of other vertebrates. Optogenetic stimulation of the PBG induces freezing and escape in mice, a result thought to be caused by a PBG projection to the central nucleus of the amygdala. However, the isthmic complex, including the PBG, has been classically considered satellite nuclei of the Superior Colliculus (SC), which upon stimulation of its medial part also triggers fear and avoidance reactions. As the PBG-SC connectivity is not well characterized, we investigated whether the topology of the PBG projection to the SC could be related to the behavioral consequences of PBG stimulation. To that end, we performed immunohistochemistry, in situ hybridization and neural tracer injections in the SC and PBG in a diurnal rodent, the Octodon degus. We found that all PBG neurons expressed both glutamatergic and cholinergic markers and were distributed in clearly defined anterior (aPBG) and posterior (pPBG) subdivisions. The pPBG is connected reciprocally and topographically to the ipsilateral SC, whereas the aPBG receives afferent axons from the ipsilateral SC and projected exclusively to the contralateral SC. This contralateral projection forms a dense field of terminals that is restricted to the medial SC, in correspondence with the SC representation of the aerial binocular field which, we also found, in O. degus prompted escape reactions upon looming stimulation. Therefore, this specialized topography allows binocular interactions in the SC region controlling responses to aerial predators, suggesting a link between the mechanisms by which the SC and PBG produce defensive behaviors. AU - Deichler, Alfonso AU - Carrasco, Denisse AU - Lopez-Jury, Luciana AU - Vega Zuniga, Tomas A AU - Marquez, Natalia AU - Mpodozis, Jorge AU - Marin, Gonzalo ID - 8643 JF - Scientific Reports TI - A specialized reciprocal connectivity suggests a link between the mechanisms by which the superior colliculus and parabigeminal nucleus produce defensive behaviors in rodents VL - 10 ER - TY - JOUR AB - Epistasis, the context-dependence of the contribution of an amino acid substitution to fitness, is common in evolution. To detect epistasis, fitness must be measured for at least four genotypes: the reference genotype, two different single mutants and a double mutant with both of the single mutations. For higher-order epistasis of the order n, fitness has to be measured for all 2n genotypes of an n-dimensional hypercube in genotype space forming a ‘combinatorially complete dataset’. So far, only a handful of such datasets have been produced by manual curation. Concurrently, random mutagenesis experiments have produced measurements of fitness and other phenotypes in a high-throughput manner, potentially containing a number of combinatorially complete datasets. We present an effective recursive algorithm for finding all hypercube structures in random mutagenesis experimental data. To test the algorithm, we applied it to the data from a recent HIS3 protein dataset and found all 199 847 053 unique combinatorially complete genotype combinations of dimensionality ranging from 2 to 12. The algorithm may be useful for researchers looking for higher-order epistasis in their high-throughput experimental data. AU - Esteban, Laura A AU - Lonishin, Lyubov R AU - Bobrovskiy, Daniil M AU - Leleytner, Gregory AU - Bogatyreva, Natalya S AU - Kondrashov, Fyodor AU - Ivankov, Dmitry N ID - 8645 IS - 6 JF - Bioinformatics SN - 1367-4803 TI - HypercubeME: Two hundred million combinatorially complete datasets from a single experiment VL - 36 ER - TY - JOUR AB - Error analysis and data visualization of positive COVID-19 cases in 27 countries have been performed up to August 8, 2020. This survey generally observes a progression from early exponential growth transitioning to an intermediate power-law growth phase, as recently suggested by Ziff and Ziff. The occurrence of logistic growth after the power-law phase with lockdowns or social distancing may be described as an effect of avoidance. A visualization of the power-law growth exponent over short time windows is qualitatively similar to the Bhatia visualization for pandemic progression. Visualizations like these can indicate the onset of second waves and may influence social policy. AU - Merrin, Jack ID - 8597 IS - 6 JF - Physical Biology TI - Differences in power law growth over time and indicators of COVID-19 pandemic progression worldwide VL - 17 ER - TY - JOUR AB - Extrasynaptic actions of glutamate are limited by high-affinity transporters expressed by perisynaptic astroglial processes (PAPs): this helps maintain point-to-point transmission in excitatory circuits. Memory formation in the brain is associated with synaptic remodeling, but how this affects PAPs and therefore extrasynaptic glutamate actions is poorly understood. Here, we used advanced imaging methods, in situ and in vivo, to find that a classical synaptic memory mechanism, long-term potentiation (LTP), triggers withdrawal of PAPs from potentiated synapses. Optical glutamate sensors combined with patch-clamp and 3D molecular localization reveal that LTP induction thus prompts spatial retreat of astroglial glutamate transporters, boosting glutamate spillover and NMDA-receptor-mediated inter-synaptic cross-talk. The LTP-triggered PAP withdrawal involves NKCC1 transporters and the actin-controlling protein cofilin but does not depend on major Ca2+-dependent cascades in astrocytes. We have therefore uncovered a mechanism by which a memory trace at one synapse could alter signal handling by multiple neighboring connections. AU - Henneberger, Christian AU - Bard, Lucie AU - Panatier, Aude AU - Reynolds, James P. AU - Kopach, Olga AU - Medvedev, Nikolay I. AU - Minge, Daniel AU - Herde, Michel K. AU - Anders, Stefanie AU - Kraev, Igor AU - Heller, Janosch P. AU - Rama, Sylvain AU - Zheng, Kaiyu AU - Jensen, Thomas P. AU - Sanchez-Romero, Inmaculada AU - Jackson, Colin J. AU - Janovjak, Harald L AU - Ottersen, Ole Petter AU - Nagelhus, Erlend Arnulf AU - Oliet, Stephane H.R. AU - Stewart, Michael G. AU - Nägerl, U. VAlentin AU - Rusakov, Dmitri A. ID - 8674 IS - 5 JF - Neuron SN - 08966273 TI - LTP induction boosts glutamate spillover by driving withdrawal of perisynaptic astroglia VL - 108 ER - TY - JOUR AB - Nature creates electrons with two values of the spin projection quantum number. In certain applications, it is important to filter electrons with one spin projection from the rest. Such filtering is not trivial, since spin-dependent interactions are often weak, and cannot lead to any substantial effect. Here we propose an efficient spin filter based upon scattering from a two-dimensional crystal, which is made of aligned point magnets. The polarization of the outgoing electron flux is controlled by the crystal, and reaches maximum at specific values of the parameters. In our scheme, polarization increase is accompanied by higher reflectivity of the crystal. High transmission is feasible in scattering from a quantum cavity made of two crystals. Our findings can be used for studies of low-energy spin-dependent scattering from two-dimensional ordered structures made of magnetic atoms or aligned chiral molecules. AU - Ghazaryan, Areg AU - Lemeshko, Mikhail AU - Volosniev, Artem ID - 8652 JF - Communications Physics SN - 2399-3650 TI - Filtering spins by scattering from a lattice of point magnets VL - 3 ER - TY - JOUR AB - Pancreatic islets play an essential role in regulating blood glucose level. Although the molecular pathways underlying islet cell differentiation are beginning to be resolved, the cellular basis of islet morphogenesis and fate allocation remain unclear. By combining unbiased and targeted lineage tracing, we address the events leading to islet formation in the mouse. From the statistical analysis of clones induced at multiple embryonic timepoints, here we show that, during the secondary transition, islet formation involves the aggregation of multiple equipotent endocrine progenitors that transition from a phase of stochastic amplification by cell division into a phase of sublineage restriction and limited islet fission. Together, these results explain quantitatively the heterogeneous size distribution and degree of polyclonality of maturing islets, as well as dispersion of progenitors within and between islets. Further, our results show that, during the secondary transition, α- and β-cells are generated in a contemporary manner. Together, these findings provide insight into the cellular basis of islet development. AU - Sznurkowska, Magdalena K. AU - Hannezo, Edouard B AU - Azzarelli, Roberta AU - Chatzeli, Lemonia AU - Ikeda, Tatsuro AU - Yoshida, Shosei AU - Philpott, Anna AU - Simons, Benjamin D ID - 8669 JF - Nature Communications TI - Tracing the cellular basis of islet specification in mouse pancreas VL - 11 ER - TY - JOUR AB - Cell fate transitions are key to development and homeostasis. It is thus essential to understand the cellular mechanisms controlling fate transitions. Cell division has been implicated in fate decisions in many stem cell types, including neuronal and epithelial progenitors. In other stem cells, such as embryonic stem (ES) cells, the role of division remains unclear. Here, we show that exit from naive pluripotency in mouse ES cells generally occurs after a division. We further show that exit timing is strongly correlated between sister cells, which remain connected by cytoplasmic bridges long after division, and that bridge abscission progressively accelerates as cells exit naive pluripotency. Finally, interfering with abscission impairs naive pluripotency exit, and artificially inducing abscission accelerates it. Altogether, our data indicate that a switch in the division machinery leading to faster abscission regulates pluripotency exit. Our study identifies abscission as a key cellular process coupling cell division to fate transitions. AU - Chaigne, Agathe AU - Labouesse, Céline AU - White, Ian J. AU - Agnew, Meghan AU - Hannezo, Edouard B AU - Chalut, Kevin J. AU - Paluch, Ewa K. ID - 8672 IS - 2 JF - Developmental Cell SN - 15345807 TI - Abscission couples cell division to embryonic stem cell fate VL - 55 ER - TY - JOUR AB - In the computation of the material properties of random alloys, the method of 'special quasirandom structures' attempts to approximate the properties of the alloy on a finite volume with higher accuracy by replicating certain statistics of the random atomic lattice in the finite volume as accurately as possible. In the present work, we provide a rigorous justification for a variant of this method in the framework of the Thomas–Fermi–von Weizsäcker (TFW) model. Our approach is based on a recent analysis of a related variance reduction method in stochastic homogenization of linear elliptic PDEs and the locality properties of the TFW model. Concerning the latter, we extend an exponential locality result by Nazar and Ortner to include point charges, a result that may be of independent interest. AU - Fischer, Julian L AU - Kniely, Michael ID - 8697 IS - 11 JF - Nonlinearity SN - 09517715 TI - Variance reduction for effective energies of random lattices in the Thomas-Fermi-von Weizsäcker model VL - 33 ER - TY - JOUR AB - Animal development entails the organization of specific cell types in space and time, and spatial patterns must form in a robust manner. In the zebrafish spinal cord, neural progenitors form stereotypic patterns despite noisy morphogen signaling and large-scale cellular rearrangements during morphogenesis and growth. By directly measuring adhesion forces and preferences for three types of endogenous neural progenitors, we provide evidence for the differential adhesion model in which differences in intercellular adhesion mediate cell sorting. Cell type–specific combinatorial expression of different classes of cadherins (N-cadherin, cadherin 11, and protocadherin 19) results in homotypic preference ex vivo and patterning robustness in vivo. Furthermore, the differential adhesion code is regulated by the sonic hedgehog morphogen gradient. We propose that robust patterning during tissue morphogenesis results from interplay between adhesion-based self-organization and morphogen-directed patterning. AU - Tsai, Tony Y.-C. AU - Sikora, Mateusz K AU - Xia, Peng AU - Colak-Champollion, Tugba AU - Knaut, Holger AU - Heisenberg, Carl-Philipp J AU - Megason, Sean G. ID - 8680 IS - 6512 JF - Science KW - Multidisciplinary SN - 0036-8075 TI - An adhesion code ensures robust pattern formation during tissue morphogenesis VL - 370 ER - TY - JOUR AB - Dynamic changes in the three-dimensional (3D) organization of chromatin are associated with central biological processes, such as transcription, replication and development. Therefore, the comprehensive identification and quantification of these changes is fundamental to understanding of evolutionary and regulatory mechanisms. Here, we present Comparison of Hi-C Experiments using Structural Similarity (CHESS), an algorithm for the comparison of chromatin contact maps and automatic differential feature extraction. We demonstrate the robustness of CHESS to experimental variability and showcase its biological applications on (1) interspecies comparisons of syntenic regions in human and mouse models; (2) intraspecies identification of conformational changes in Zelda-depleted Drosophila embryos; (3) patient-specific aberrant chromatin conformation in a diffuse large B-cell lymphoma sample; and (4) the systematic identification of chromatin contact differences in high-resolution Capture-C data. In summary, CHESS is a computationally efficient method for the comparison and classification of changes in chromatin contact data. AU - Galan, Silvia AU - Machnik, Nick N AU - Kruse, Kai AU - Díaz, Noelia AU - Marti-Renom, Marc A AU - Vaquerizas, Juan M ID - 8707 JF - Nature Genetics SN - 10614036 TI - CHESS enables quantitative comparison of chromatin contact data and automatic feature extraction VL - 52 ER - TY - JOUR AB - A central goal of artificial intelligence in high-stakes decision-making applications is to design a single algorithm that simultaneously expresses generalizability by learning coherent representations of their world and interpretable explanations of its dynamics. Here, we combine brain-inspired neural computation principles and scalable deep learning architectures to design compact neural controllers for task-specific compartments of a full-stack autonomous vehicle control system. We discover that a single algorithm with 19 control neurons, connecting 32 encapsulated input features to outputs by 253 synapses, learns to map high-dimensional inputs into steering commands. This system shows superior generalizability, interpretability and robustness compared with orders-of-magnitude larger black-box learning systems. The obtained neural agents enable high-fidelity autonomy for task-specific parts of a complex autonomous system. AU - Lechner, Mathias AU - Hasani, Ramin AU - Amini, Alexander AU - Henzinger, Thomas A AU - Rus, Daniela AU - Grosu, Radu ID - 8679 JF - Nature Machine Intelligence TI - Neural circuit policies enabling auditable autonomy VL - 2 ER - TY - JOUR AB - The α–z Rényi relative entropies are a two-parameter family of Rényi relative entropies that are quantum generalizations of the classical α-Rényi relative entropies. In the work [Adv. Math. 365, 107053 (2020)], we decided the full range of (α, z) for which the data processing inequality (DPI) is valid. In this paper, we give algebraic conditions for the equality in DPI. For the full range of parameters (α, z), we give necessary conditions and sufficient conditions. For most parameters, we give equivalent conditions. This generalizes and strengthens the results of Leditzky et al. [Lett. Math. Phys. 107, 61–80 (2017)]. AU - Zhang, Haonan ID - 8670 IS - 10 JF - Journal of Mathematical Physics SN - 00222488 TI - Equality conditions of data processing inequality for α-z Rényi relative entropies VL - 61 ER - TY - JOUR AB - The brain represents and reasons probabilistically about complex stimuli and motor actions using a noisy, spike-based neural code. A key building block for such neural computations, as well as the basis for supervised and unsupervised learning, is the ability to estimate the surprise or likelihood of incoming high-dimensional neural activity patterns. Despite progress in statistical modeling of neural responses and deep learning, current approaches either do not scale to large neural populations or cannot be implemented using biologically realistic mechanisms. Inspired by the sparse and random connectivity of real neuronal circuits, we present a model for neural codes that accurately estimates the likelihood of individual spiking patterns and has a straightforward, scalable, efficient, learnable, and realistic neural implementation. This model’s performance on simultaneously recorded spiking activity of >100 neurons in the monkey visual and prefrontal cortices is comparable with or better than that of state-of-the-art models. Importantly, the model can be learned using a small number of samples and using a local learning rule that utilizes noise intrinsic to neural circuits. Slower, structural changes in random connectivity, consistent with rewiring and pruning processes, further improve the efficiency and sparseness of the resulting neural representations. Our results merge insights from neuroanatomy, machine learning, and theoretical neuroscience to suggest random sparse connectivity as a key design principle for neuronal computation. AU - Maoz, Ori AU - Tkačik, Gašper AU - Esteki, Mohamad Saleh AU - Kiani, Roozbeh AU - Schneidman, Elad ID - 8698 IS - 40 JF - Proceedings of the National Academy of Sciences of the United States of America SN - 00278424 TI - Learning probabilistic neural representations with randomly connected circuits VL - 117 ER - TY - CONF AB - Traditional robotic control suits require profound task-specific knowledge for designing, building and testing control software. The rise of Deep Learning has enabled end-to-end solutions to be learned entirely from data, requiring minimal knowledge about the application area. We design a learning scheme to train end-to-end linear dynamical systems (LDS)s by gradient descent in imitation learning robotic domains. We introduce a new regularization loss component together with a learning algorithm that improves the stability of the learned autonomous system, by forcing the eigenvalues of the internal state updates of an LDS to be negative reals. We evaluate our approach on a series of real-life and simulated robotic experiments, in comparison to linear and nonlinear Recurrent Neural Network (RNN) architectures. Our results show that our stabilizing method significantly improves test performance of LDS, enabling such linear models to match the performance of contemporary nonlinear RNN architectures. A video of the obstacle avoidance performance of our method on a mobile robot, in unseen environments, compared to other methods can be viewed at https://youtu.be/mhEsCoNao5E. AU - Lechner, Mathias AU - Hasani, Ramin AU - Rus, Daniela AU - Grosu, Radu ID - 8704 SN - 10504729 T2 - Proceedings - IEEE International Conference on Robotics and Automation TI - Gershgorin loss stabilizes the recurrent neural network compartment of an end-to-end robot learning scheme ER - TY - JOUR AB - Translation termination is a finishing step of protein biosynthesis. The significant role in this process belongs not only to protein factors of translation termination but also to the nearest nucleotide environment of stop codons. There are numerous descriptions of stop codons readthrough, which is due to specific nucleotide sequences behind them. However, represented data are segmental and don’t explain the mechanism of the nucleotide context influence on translation termination. It is well known that stop codon UAA usage is preferential for A/T-rich genes, and UAG, UGA—for G/C-rich genes, which is related to an expression level of these genes. We investigated the connection between a frequency of nucleotides occurrence in 3' area of stop codons in the human genome and their influence on translation termination efficiency. We found that 3' context motif, which is cognate to the sequence of a stop codon, stimulates translation termination. At the same time, the nucleotide composition of 3' sequence that differs from stop codon, decreases translation termination efficiency. AU - Sokolova, E. E. AU - Vlasov, Petr AU - Egorova, T. V. AU - Shuvalov, A. V. AU - Alkalaeva, E. Z. ID - 8700 IS - 5 JF - Molecular Biology SN - 00268933 TI - The influence of A/G composition of 3' stop codon contexts on translation termination efficiency in eukaryotes VL - 54 ER - TY - JOUR AB - Translation termination is a finishing step of protein biosynthesis. The significant role in this process belongs not only to protein factors of translation termination but also to the nearest nucleotide environment of stop codons. There are numerous descriptions of stop codons readthrough, which is due to specific nucleotide sequences behind them. However, represented data are segmental and don’t explain the mechanism of the nucleotide context influence on translation termination. It is well known that stop codon UAA usage is preferential for A/T-rich genes, and UAG, UGA—for G/C-rich genes, which is related to an expression level of these genes. We investigated the connection between a frequency of nucleotides occurrence in 3' area of stop codons in the human genome and their influence on translation termination efficiency. We found that 3' context motif, which is cognate to the sequence of a stop codon, stimulates translation termination. At the same time, the nucleotide composition of 3' sequence that differs from stop codon, decreases translation termination efficiency. AU - Sokolova, E. E. AU - Vlasov, Petr AU - Egorova, T. V. AU - Shuvalov, A. V. AU - Alkalaeva, E. Z. ID - 8701 IS - 5 JF - Molekuliarnaia biologiia SN - 00268984 TI - The influence of A/G composition of 3' stop codon contexts on translation termination efficiency in eukaryotes VL - 54 ER - TY - GEN AB - A binary neutron star merger has been observed in a multi-messenger detection of gravitational wave (GW) and electromagnetic (EM) radiation. Binary neutron stars that merge within a Hubble time, as well as many other compact binaries, are expected to form via common envelope evolution. Yet five decades of research on common envelope evolution have not yet resulted in a satisfactory understanding of the multi-spatial multi-timescale evolution for the systems that lead to compact binaries. In this paper, we report on the first successful simulations of common envelope ejection leading to binary neutron star formation in 3D hydrodynamics. We simulate the dynamical inspiral phase of the interaction between a 12M⊙ red supergiant and a 1.4M⊙ neutron star for different initial separations and initial conditions. For all of our simulations, we find complete envelope ejection and final orbital separations of af≈1.3-5.1R⊙ depending on the simulation and criterion, leading to binary neutron stars that can merge within a Hubble time. We find αCE-equivalent efficiencies of ≈0.1-2.7 depending on the simulation and criterion, but this may be specific for these extended progenitors. We fully resolve the core of the star to ≲0.005R⊙ and our 3D hydrodynamics simulations are informed by an adjusted 1D analytic energy formalism and a 2D kinematics study in order to overcome the prohibitive computational cost of simulating these systems. The framework we develop in this paper can be used to simulate a wide variety of interactions between stars, from stellar mergers to common envelope episodes leading to GW sources. AU - Jamie A. P. Law-Smith, Jamie A. P. Law-Smith AU - Everson, Rosa Wallace AU - Enrico Ramirez-Ruiz, Enrico Ramirez-Ruiz AU - Mink, Selma E. de AU - Son, Lieke A. C. van AU - Götberg, Ylva Louise Linsdotter AU - Zellmann, Stefan AU - Alejandro Vigna-Gómez, Alejandro Vigna-Gómez AU - Renzo, Mathieu AU - Wu, Samantha AU - Schrøder, Sophie L. AU - Foley, Ryan J. AU - Tenley Hutchinson-Smith, Tenley Hutchinson-Smith ID - 14096 T2 - arXiv TI - Successful common envelope ejection and binary neutron star formation in 3D hydrodynamics ER -