TY - JOUR
AB - Mutations in NDUFS4, which encodes an accessory subunit of mitochondrial oxidative phosphorylation (OXPHOS) complex I (CI), induce Leigh syndrome (LS). LS is a poorly understood pediatric disorder featuring brain-specific anomalies and early death. To study the LS pathomechanism, we here compared OXPHOS proteomes between various Ndufs4−/− mouse tissues. Ndufs4−/− animals displayed significantly lower CI subunit levels in brain/diaphragm relative to other tissues (liver/heart/kidney/skeletal muscle), whereas other OXPHOS subunit levels were not reduced. Absence of NDUFS4 induced near complete absence of the NDUFA12 accessory subunit, a 50% reduction in other CI subunit levels, and an increase in specific CI assembly factors. Among the latter, NDUFAF2 was most highly increased. Regarding NDUFS4, NDUFA12 and NDUFAF2, identical results were obtained in Ndufs4−/− mouse embryonic fibroblasts (MEFs) and NDUFS4-mutated LS patient cells. Ndufs4−/− MEFs contained active CI in situ but blue-native-PAGE highlighted that NDUFAF2 attached to an inactive CI subcomplex (CI-830) and inactive assemblies of higher MW. In NDUFA12-mutated LS patient cells, NDUFA12 absence did not reduce NDUFS4 levels but triggered NDUFAF2 association to active CI. BN-PAGE revealed no such association in LS patient fibroblasts with mutations in other CI subunit-encoding genes where NDUFAF2 was attached to CI-830 (NDUFS1, NDUFV1 mutation) or not detected (NDUFS7 mutation). Supported by enzymological and CI in silico structural analysis, we conclude that absence of NDUFS4 induces near complete absence of NDUFA12 but not vice versa, and that NDUFAF2 stabilizes active CI in Ndufs4−/− mice and LS patient cells, perhaps in concert with mitochondrial inner membrane lipids.
AU - Adjobo-Hermans, Merel J.W.
AU - De Haas, Ria
AU - Willems, Peter H.G.M.
AU - Wojtala, Aleksandra
AU - Van Emst-De Vries, Sjenet E.
AU - Wagenaars, Jori A.
AU - Van Den Brand, Mariel
AU - Rodenburg, Richard J.
AU - Smeitink, Jan A.M.
AU - Nijtmans, Leo G.
AU - Sazanov, Leonid A
AU - Wieckowski, Mariusz R.
AU - Koopman, Werner J.H.
ID - 7788
IS - 8
JF - Biochimica et Biophysica Acta - Bioenergetics
SN - 00052728
TI - NDUFS4 deletion triggers loss of NDUFA12 in Ndufs4−/− mice and Leigh syndrome patients: A stabilizing role for NDUFAF2
VL - 1861
ER -
TY - JOUR
AB - During embryonic and postnatal development, organs and tissues grow steadily to achieve their final size at the end of puberty. However, little is known about the cellular dynamics that mediate postnatal growth. By combining in vivo clonal lineage tracing, proliferation kinetics, single-cell transcriptomics, andin vitro micro-pattern experiments, we resolved the cellular dynamics taking place during postnatal skin epidermis expansion. Our data revealed that harmonious growth is engineered by a single population of developmental progenitors presenting a fixed fate imbalance of self-renewing divisions with an ever-decreasing proliferation rate. Single-cell RNA sequencing revealed that epidermal developmental progenitors form a more uniform population compared with adult stem and progenitor cells. Finally, we found that the spatial pattern of cell division orientation is dictated locally by the underlying collagen fiber orientation. Our results uncover a simple design principle of organ growth where progenitors and differentiated cells expand in harmony with their surrounding tissues.
AU - Dekoninck, Sophie
AU - Hannezo, Edouard B
AU - Sifrim, Alejandro
AU - Miroshnikova, Yekaterina A.
AU - Aragona, Mariaceleste
AU - Malfait, Milan
AU - Gargouri, Souhir
AU - De Neunheuser, Charlotte
AU - Dubois, Christine
AU - Voet, Thierry
AU - Wickström, Sara A.
AU - Simons, Benjamin D.
AU - Blanpain, Cédric
ID - 7789
IS - 3
JF - Cell
SN - 00928674
TI - Defining the design principles of skin epidermis postnatal growth
VL - 181
ER -
TY - JOUR
AB - We prove a lower bound for the free energy (per unit volume) of the two-dimensional Bose gas in the thermodynamic limit. We show that the free energy at density 𝜌 and inverse temperature 𝛽 differs from the one of the noninteracting system by the correction term 𝜋𝜌𝜌𝛽𝛽 . Here, is the scattering length of the interaction potential, and 𝛽 is the inverse Berezinskii–Kosterlitz–Thouless critical temperature for superfluidity. The result is valid in the dilute limit 𝜌 and if 𝛽𝜌 .
AU - Deuchert, Andreas
AU - Mayer, Simon
AU - Seiringer, Robert
ID - 7790
JF - Forum of Mathematics, Sigma
TI - The free energy of the two-dimensional dilute Bose gas. I. Lower bound
VL - 8
ER -
TY - JOUR
AB - Extending a result of Milena Radnovic and Serge Tabachnikov, we establish conditionsfor two different non-symmetric norms to define the same billiard reflection law.
AU - Akopyan, Arseniy
AU - Karasev, Roman
ID - 7791
JF - European Journal of Mathematics
SN - 2199675X
TI - When different norms lead to same billiard trajectories?
ER -
TY - JOUR
AB - Hormonal signalling in animals often involves direct transcription factor-hormone interactions that modulate gene expression. In contrast, plant hormone signalling is most commonly based on de-repression via the degradation of transcriptional repressors. Recently, we uncovered a non-canonical signalling mechanism for the plant hormone auxin whereby auxin directly affects the activity of the atypical auxin response factor (ARF), ETTIN towards target genes without the requirement for protein degradation. Here we show that ETTIN directly binds auxin, leading to dissociation from co-repressor proteins of the TOPLESS/TOPLESS-RELATED family followed by histone acetylation and induction of gene expression. This mechanism is reminiscent of animal hormone signalling as it affects the activity towards regulation of target genes and provides the first example of a DNA-bound hormone receptor in plants. Whilst auxin affects canonical ARFs indirectly by facilitating degradation of Aux/IAA repressors, direct ETTIN-auxin interactions allow switching between repressive and de-repressive chromatin states in an instantly-reversible manner.
AU - Kuhn, André
AU - Ramans Harborough, Sigurd
AU - McLaughlin, Heather M
AU - Natarajan, Bhavani
AU - Verstraeten, Inge
AU - Friml, Jiří
AU - Kepinski, Stefan
AU - Østergaard, Lars
ID - 7793
JF - eLife
SN - 2050-084X
TI - Direct ETTIN-auxin interaction controls chromatin states in gynoecium development
VL - 9
ER -
TY - CONF
AB - The Massively Parallel Computation (MPC) model is an emerging model which distills core aspects of distributed and parallel computation. It has been developed as a tool to solve (typically graph) problems in systems where the input is distributed over many machines with limited space.
Recent work has focused on the regime in which machines have sublinear (in $n$, the number of nodes in the input graph) space, with randomized algorithms presented for fundamental graph problems of Maximal Matching and Maximal Independent Set. However, there have been no prior corresponding deterministic algorithms.
A major challenge underlying the sublinear space setting is that the local space of each machine might be too small to store all the edges incident to a single node. This poses a considerable obstacle compared to the classical models in which each node is assumed to know and have easy access to its incident edges. To overcome this barrier we introduce a new graph sparsification technique that deterministically computes a low-degree subgraph with additional desired properties. The degree of the nodes in this subgraph is small in the sense that the edges of each node can be now stored on a single machine. This low-degree subgraph also has the property that solving the problem on this subgraph provides \emph{significant} global progress, i.e., progress towards solving the problem for the original input graph.
Using this framework to derandomize the well-known randomized algorithm of Luby [SICOMP'86], we obtain $O(\log \Delta+\log\log n)$-round deterministic MPC algorithms for solving the fundamental problems of Maximal Matching and Maximal Independent Set with $O(n^{\epsilon})$ space on each machine for any constant $\epsilon > 0$. Based on the recent work of Ghaffari et al. [FOCS'18], this additive $O(\log\log n)$ factor is conditionally essential. These algorithms can also be shown to run in $O(\log \Delta)$ rounds in the closely related model of CONGESTED CLIQUE, improving upon the state-of-the-art bound of $O(\log^2 \Delta)$ rounds by Censor-Hillel et al. [DISC'17].
AU - Czumaj, Artur
AU - Davies, Peter
AU - Parter, Merav
ID - 7802
IS - 7
T2 - Proceedings of the 32nd ACM Symposium on Parallelism in Algorithms and Architectures (SPAA 2020)
TI - Graph sparsification for derandomizing massively parallel computation with low space
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 - CONF
AB - We consider the following decision problem EMBEDk→d in computational topology (where k ≤ d are fixed positive integers): Given a finite simplicial complex K of dimension k, does there exist a (piecewise-linear) embedding of K into ℝd?
The special case EMBED1→2 is graph planarity, which is decidable in linear time, as shown by Hopcroft and Tarjan. In higher dimensions, EMBED2→3 and EMBED3→3 are known to be decidable (as well as NP-hard), and recent results of Čadek et al. in computational homotopy theory, in combination with the classical Haefliger–Weber theorem in geometric topology, imply that EMBEDk→d can be solved in polynomial time for any fixed pair (k, d) of dimensions in the so-called metastable range .
Here, by contrast, we prove that EMBEDk→d is algorithmically undecidable for almost all pairs of dimensions outside the metastable range, namely for . This almost completely resolves the decidability vs. undecidability of EMBEDk→d in higher dimensions and establishes a sharp dichotomy between polynomial-time solvability and undecidability.
Our result complements (and in a wide range of dimensions strengthens) earlier results of Matoušek, Tancer, and the second author, who showed that EMBEDk→d is undecidable for 4 ≤ k ϵ {d – 1, d}, and NP-hard for all remaining pairs (k, d) outside the metastable range and satisfying d ≥ 4.
AU - Filakovský, Marek
AU - Wagner, Uli
AU - Zhechev, Stephan Y
ID - 7806
SN - 9781611975994
T2 - Proceedings of the Annual ACM-SIAM Symposium on Discrete Algorithms
TI - Embeddability of simplicial complexes is undecidable
VL - 2020-January
ER -
TY - CONF
AB - In a straight-line embedded triangulation of a point set P in the plane, removing an inner edge and—provided the resulting quadrilateral is convex—adding the other diagonal is called an edge flip. The (edge) flip graph has all triangulations as vertices, and a pair of triangulations is adjacent if they can be obtained from each other by an edge flip. The goal of this paper is to contribute to a better understanding of the flip graph, with an emphasis on its connectivity.
For sets in general position, it is known that every triangulation allows at least edge flips (a tight bound) which gives the minimum degree of any flip graph for n points. We show that for every point set P in general position, the flip graph is at least -vertex connected. Somewhat more strongly, we show that the vertex connectivity equals the minimum degree occurring in the flip graph, i.e. the minimum number of flippable edges in any triangulation of P, provided P is large enough. Finally, we exhibit some of the geometry of the flip graph by showing that the flip graph can be covered by 1-skeletons of polytopes of dimension (products of associahedra).
A corresponding result ((n – 3)-vertex connectedness) can be shown for the bistellar flip graph of partial triangulations, i.e. the set of all triangulations of subsets of P which contain all extreme points of P. This will be treated separately in a second part.
AU - Wagner, Uli
AU - Welzl, Emo
ID - 7807
SN - 9781611975994
T2 - Proceedings of the Annual ACM-SIAM Symposium on Discrete Algorithms
TI - Connectivity of triangulation flip graphs in the plane (Part I: Edge flips)
VL - 2020-January
ER -
TY - CONF
AB - Quantization converts neural networks into low-bit fixed-point computations which can be carried out by efficient integer-only hardware, and is standard practice for the deployment of neural networks on real-time embedded devices. However, like their real-numbered counterpart, quantized networks are not immune to malicious misclassification caused by adversarial attacks. We investigate how quantization affects a network’s robustness to adversarial attacks, which is a formal verification question. We show that neither robustness nor non-robustness are monotonic with changing the number of bits for the representation and, also, neither are preserved by quantization from a real-numbered network. For this reason, we introduce a verification method for quantized neural networks which, using SMT solving over bit-vectors, accounts for their exact, bit-precise semantics. We built a tool and analyzed the effect of quantization on a classifier for the MNIST dataset. We demonstrate that, compared to our method, existing methods for the analysis of real-numbered networks often derive false conclusions about their quantizations, both when determining robustness and when detecting attacks, and that existing methods for quantized networks often miss attacks. Furthermore, we applied our method beyond robustness, showing how the number of bits in quantization enlarges the gender bias of a predictor for students’ grades.
AU - Giacobbe, Mirco
AU - Henzinger, Thomas A
AU - Lechner, Mathias
ID - 7808
SN - 03029743
T2 - International Conference on Tools and Algorithms for the Construction and Analysis of Systems
TI - How many bits does it take to quantize your neural network?
VL - 12079
ER -
TY - CONF
AB - Interprocedural data-flow analyses form an expressive and useful paradigm of numerous static analysis applications, such as live variables analysis, alias analysis and null pointers analysis. The most widely-used framework for interprocedural data-flow analysis is IFDS, which encompasses distributive data-flow functions over a finite domain. On-demand data-flow analyses restrict the focus of the analysis on specific program locations and data facts. This setting provides a natural split between (i) an offline (or preprocessing) phase, where the program is partially analyzed and analysis summaries are created, and (ii) an online (or query) phase, where analysis queries arrive on demand and the summaries are used to speed up answering queries.
In this work, we consider on-demand IFDS analyses where the queries concern program locations of the same procedure (aka same-context queries). We exploit the fact that flow graphs of programs have low treewidth to develop faster algorithms that are space and time optimal for many common data-flow analyses, in both the preprocessing and the query phase. We also use treewidth to develop query solutions that are embarrassingly parallelizable, i.e. the total work for answering each query is split to a number of threads such that each thread performs only a constant amount of work. Finally, we implement a static analyzer based on our algorithms, and perform a series of on-demand analysis experiments on standard benchmarks. Our experimental results show a drastic speed-up of the queries after only a lightweight preprocessing phase, which significantly outperforms existing techniques.
AU - Chatterjee, Krishnendu
AU - Goharshady, Amir Kafshdar
AU - Ibsen-Jensen, Rasmus
AU - Pavlogiannis, Andreas
ID - 7810
SN - 03029743
T2 - European Symposium on Programming
TI - Optimal and perfectly parallel algorithms for on-demand data-flow analysis
VL - 12075
ER -
TY - JOUR
AB - Scientific research is to date largely restricted to wealthy laboratories in developed nations due to the necessity of complex and expensive equipment. This inequality limits the capacity of science to be used as a diplomatic channel. Maker movements use open-source technologies including additive manufacturing (3D printing) and laser cutting, together with low-cost computers for developing novel products. This movement is setting the groundwork for a revolution, allowing scientific equipment to be sourced at a fraction of the cost and has the potential to increase the availability of equipment for scientists around the world. Science education is increasingly recognized as another channel for science diplomacy. In this perspective, we introduce the idea that the Maker movement and open-source technologies have the potential to revolutionize science, technology, engineering and mathematics (STEM) education worldwide. We present an open-source STEM didactic tool called SCOPES (Sparking Curiosity through Open-source Platforms in Education and Science). SCOPES is self-contained, independent of local resources, and cost-effective. SCOPES can be adapted to communicate complex subjects from genetics to neurobiology, perform real-world biological experiments and explore digitized scientific samples. We envision such platforms will enhance science diplomacy by providing a means for scientists to share their findings with classrooms and for educators to incorporate didactic concepts into STEM lessons. By providing students the opportunity to design, perform, and share scientific experiments, students also experience firsthand the benefits of a multinational scientific community. We provide instructions on how to build and use SCOPES on our webpage: http://scopeseducation.org.
AU - Beattie, Robert J
AU - Hippenmeyer, Simon
AU - Pauler, Florian
ID - 7814
JF - Frontiers in Education
SN - 2504-284X
TI - SCOPES: Sparking curiosity through Open-Source platforms in education and science
VL - 5
ER -
TY - JOUR
AB - Beginning from a limited pool of progenitors, the mammalian cerebral cortex forms highly organized functional neural circuits. However, the underlying cellular and molecular mechanisms regulating lineage transitions of neural stem cells (NSCs) and eventual production of neurons and glia in the developing neuroepithelium remains unclear. Methods to trace NSC division patterns and map the lineage of clonally related cells have advanced dramatically. However, many contemporary lineage tracing techniques suffer from the lack of cellular resolution of progeny cell fate, which is essential for deciphering progenitor cell division patterns. Presented is a protocol using mosaic analysis with double markers (MADM) to perform in vivo clonal analysis. MADM concomitantly manipulates individual progenitor cells and visualizes precise division patterns and lineage progression at unprecedented single cell resolution. MADM-based interchromosomal recombination events during the G2-X phase of mitosis, together with temporally inducible CreERT2, provide exact information on the birth dates of clones and their division patterns. Thus, MADM lineage tracing provides unprecedented qualitative and quantitative optical readouts of the proliferation mode of stem cell progenitors at the single cell level. MADM also allows for examination of the mechanisms and functional requirements of candidate genes in NSC lineage progression. This method is unique in that comparative analysis of control and mutant subclones can be performed in the same tissue environment in vivo. Here, the protocol is described in detail, and experimental paradigms to employ MADM for clonal analysis and lineage tracing in the developing cerebral cortex are demonstrated. Importantly, this protocol can be adapted to perform MADM clonal analysis in any murine stem cell niche, as long as the CreERT2 driver is present.
AU - Beattie, Robert J
AU - Streicher, Carmen
AU - Amberg, Nicole
AU - Cheung, Giselle T
AU - Contreras, Ximena
AU - Hansen, Andi H
AU - Hippenmeyer, Simon
ID - 7815
IS - 159
JF - Journal of Visual Experiments (JoVE)
SN - 1940-087X
TI - Lineage tracing and clonal analysis in developing cerebral cortex using mosaic analysis with double markers (MADM)
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 this paper, we establish convergence to equilibrium for a drift–diffusion–recombination system modelling the charge transport within certain semiconductor devices. More precisely, we consider a two-level system for electrons and holes which is augmented by an intermediate energy level for electrons in so-called trapped states. The recombination dynamics use the mass action principle by taking into account this additional trap level. The main part of the paper is concerned with the derivation of an entropy–entropy production inequality, which entails exponential convergence to the equilibrium via the so-called entropy method. The novelty of our approach lies in the fact that the entropy method is applied uniformly in a fast-reaction parameter which governs the lifetime of electrons on the trap level. Thus, the resulting decay estimate for the densities of electrons and holes extends to the corresponding quasi-steady-state approximation.
AU - Fellner, Klemens
AU - Kniely, Michael
ID - 7866
JF - Journal of Elliptic and Parabolic Equations
SN - 22969020
TI - Uniform convergence to equilibrium for a family of drift–diffusion models with trap-assisted recombination and the limiting Shockley–Read–Hall model
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 - 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 - 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
AU - Han, Huibin
AU - Rakusová, Hana
AU - Verstraeten, Inge
AU - Zhang, Yuzhou
AU - Friml, Jiří
ID - 7879
IS - 5
JF - Plant physiology
TI - SCF TIR1/AFB auxin signaling for bending termination during shoot gravitropism
VL - 183
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 - 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 - All vertebrates have a spinal cord with dimensions and shape specific to their species. Yet how species‐specific organ size and shape are achieved is a fundamental unresolved question in biology. The formation and sculpting of organs begins during embryonic development. As it develops, the spinal cord extends in anterior–posterior direction in synchrony with the overall growth of the body. The dorsoventral (DV) and apicobasal lengths of the spinal cord neuroepithelium also change, while at the same time a characteristic pattern of neural progenitor subtypes along the DV axis is established and elaborated. At the basis of these changes in tissue size and shape are biophysical determinants, such as the change in cell number, cell size and shape, and anisotropic tissue growth. These processes are controlled by global tissue‐scale regulators, such as morphogen signaling gradients as well as mechanical forces. Current challenges in the field are to uncover how these tissue‐scale regulatory mechanisms are translated to the cellular and molecular level, and how regulation of distinct cellular processes gives rise to an overall defined size. Addressing these questions will help not only to achieve a better understanding of how size is controlled, but also of how tissue size is coordinated with the specification of pattern.
AU - Kuzmicz-Kowalska, Katarzyna
AU - Kicheva, Anna
ID - 7883
JF - Wiley Interdisciplinary Reviews: Developmental Biology
SN - 17597684
TI - Regulation of size and scale in vertebrate spinal cord development
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 - Autoluminescent plants engineered to express a bacterial bioluminescence gene cluster in plastids have not been widely adopted because of low light output. We engineered tobacco plants with a fungal bioluminescence system that converts caffeic acid (present in all plants) into luciferin and report self-sustained luminescence that is visible to the naked eye. Our findings could underpin development of a suite of imaging tools for plants.
AU - Mitiouchkina, Tatiana
AU - Mishin, Alexander S.
AU - Gonzalez Somermeyer, Louisa
AU - Markina, Nadezhda M.
AU - Chepurnyh, Tatiana V.
AU - Guglya, Elena B.
AU - Karataeva, Tatiana A.
AU - Palkina, Kseniia A.
AU - Shakhova, Ekaterina S.
AU - Fakhranurova, Liliia I.
AU - Chekova, Sofia V.
AU - Tsarkova, Aleksandra S.
AU - Golubev, Yaroslav V.
AU - Negrebetsky, Vadim V.
AU - Dolgushin, Sergey A.
AU - Shalaev, Pavel V.
AU - Shlykov, Dmitry
AU - Melnik, Olesya A.
AU - Shipunova, Victoria O.
AU - Deyev, Sergey M.
AU - Bubyrev, Andrey I.
AU - Pushin, Alexander S.
AU - Choob, Vladimir V.
AU - Dolgov, Sergey V.
AU - Kondrashov, Fyodor
AU - Yampolsky, Ilia V.
AU - Sarkisyan, Karen S.
ID - 7889
JF - Nature Biotechnology
SN - 1087-0156
TI - Plants with genetically encoded autoluminescence
VL - 38
ER -
TY - JOUR
AB - Hartree–Fock theory has been justified as a mean-field approximation for fermionic systems. However, it suffers from some defects in predicting physical properties, making necessary a theory of quantum correlations. Recently, bosonization of many-body correlations has been rigorously justified as an upper bound on the correlation energy at high density with weak interactions. We review the bosonic approximation, deriving an effective Hamiltonian. We then show that for systems with Coulomb interaction this effective theory predicts collective excitations (plasmons) in accordance with the random phase approximation of Bohm and Pines, and with experimental observation.
AU - Benedikter, Niels P
ID - 7900
JF - Reviews in Mathematical Physics
SN - 0129-055X
TI - Bosonic collective excitations in Fermi gases
ER -
TY - GEN
AB - We derive rigorously the leading order of the correlation energy of a Fermi
gas in a scaling regime of high density and weak interaction. The result
verifies the prediction of the random-phase approximation. Our proof refines
the method of collective bosonization in three dimensions. We approximately
diagonalize an effective Hamiltonian describing approximately bosonic
collective excitations around the Hartree-Fock state, while showing that
gapless and non-collective excitations have only a negligible effect on the
ground state energy.
AU - Benedikter, Niels P
AU - Nam, Phan Thành
AU - Porta, Marcello
AU - Schlein, Benjamin
AU - Seiringer, Robert
ID - 7901
T2 - ArXiv
TI - Correlation energy of a weakly interacting Fermi gas
ER -
TY - JOUR
AB - We investigate a sheaf-theoretic interpretation of stratification learning from geometric and topological perspectives. Our main result is the construction of stratification learning algorithms framed in terms of a sheaf on a partially ordered set with the Alexandroff topology. We prove that the resulting decomposition is the unique minimal stratification for which the strata are homogeneous and the given sheaf is constructible. In particular, when we choose to work with the local homology sheaf, our algorithm gives an alternative to the local homology transfer algorithm given in Bendich et al. (Proceedings of the 23rd Annual ACM-SIAM Symposium on Discrete Algorithms, pp. 1355–1370, ACM, New York, 2012), and the cohomology stratification algorithm given in Nanda (Found. Comput. Math. 20(2), 195–222, 2020). Additionally, we give examples of stratifications based on the geometric techniques of Breiding et al. (Rev. Mat. Complut. 31(3), 545–593, 2018), illustrating how the sheaf-theoretic approach can be used to study stratifications from both topological and geometric perspectives. This approach also points toward future applications of sheaf theory in the study of topological data analysis by illustrating the utility of the language of sheaf theory in generalizing existing algorithms.
AU - Brown, Adam
AU - Wang, Bei
ID - 7905
JF - Discrete & Computational Geometry
SN - 0179-5376
TI - Sheaf-theoretic stratification learning from geometric and topological perspectives
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 - 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 - Quantum illumination uses entangled signal-idler photon pairs to boost the detection efficiency of low-reflectivity objects in environments with bright thermal noise. Its advantage is particularly evident at low signal powers, a promising feature for applications such as noninvasive biomedical scanning or low-power short-range radar. Here, we experimentally investigate the concept of quantum illumination at microwave frequencies. We generate entangled fields to illuminate a room-temperature object at a distance of 1 m in a free-space detection setup. We implement a digital phase-conjugate receiver based on linear quadrature measurements that outperforms a symmetric classical noise radar in the same conditions, despite the entanglement-breaking signal path. Starting from experimental data, we also simulate the case of perfect idler photon number detection, which results in a quantum advantage compared with the relative classical benchmark. Our results highlight the opportunities and challenges in the way toward a first room-temperature application of microwave quantum circuits.
AU - Barzanjeh, Shabir
AU - Pirandola, S.
AU - Vitali, D
AU - Fink, Johannes M
ID - 7910
IS - 19
JF - Science Advances
TI - Microwave quantum illumination using a digital receiver
VL - 6
ER -
TY - JOUR
AB - We explore the time evolution of two impurities in a trapped one-dimensional Bose gas that follows a change of the boson-impurity interaction. We study the induced impurity-impurity interactions and their effect on the quench dynamics. In particular, we report on the size of the impurity cloud, the impurity-impurity entanglement, and the impurity-impurity correlation function. The presented numerical simulations are based upon the variational multilayer multiconfiguration time-dependent Hartree method for bosons. To analyze and quantify induced impurity-impurity correlations, we employ an effective two-body Hamiltonian with a contact interaction. We show that the effective model consistent with the mean-field attraction of two heavy impurities explains qualitatively our results for weak interactions. Our findings suggest that the quench dynamics in cold-atom systems can be a tool for studying impurity-impurity correlations.
AU - Mistakidis, S. I.
AU - Volosniev, Artem
AU - Schmelcher, P.
ID - 7919
JF - Physical Review Research
SN - 2643-1564
TI - Induced correlations between impurities in a one-dimensional quenched Bose gas
VL - 2
ER -
TY - JOUR
AB - In this paper, we introduce a relaxed CQ method with alternated inertial step for solving split feasibility problems. We give convergence of the sequence generated by our method under some suitable assumptions. Some numerical implementations from sparse signal and image deblurring are reported to show the efficiency of our method.
AU - Shehu, Yekini
AU - Gibali, Aviv
ID - 7925
JF - Optimization Letters
SN - 1862-4472
TI - New inertial relaxed method for solving split feasibilities
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 - Pulsating flows through tubular geometries are laminar provided that velocities are moderate. This in particular is also believed to apply to cardiovascular flows where inertial forces are typically too low to sustain turbulence. On the other hand, flow instabilities and fluctuating shear stresses are held responsible for a variety of cardiovascular diseases. Here we report a nonlinear instability mechanism for pulsating pipe flow that gives rise to bursts of turbulence at low flow rates. Geometrical distortions of small, yet finite, amplitude are found to excite a state consisting of helical vortices during flow deceleration. The resulting flow pattern grows rapidly in magnitude, breaks down into turbulence, and eventually returns to laminar when the flow accelerates. This scenario causes shear stress fluctuations and flow reversal during each pulsation cycle. Such unsteady conditions can adversely affect blood vessels and have been shown to promote inflammation and dysfunction of the shear stress-sensitive endothelial cell layer.
AU - Xu, Duo
AU - Varshney, Atul
AU - Ma, Xingyu
AU - Song, Baofang
AU - Riedl, Michael
AU - Avila, Marc
AU - Hof, Björn
ID - 7932
IS - 21
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 00278424
TI - Nonlinear hydrodynamic instability and turbulence in pulsatile flow
VL - 117
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 - We design fast deterministic algorithms for distance computation in the Congested Clique model. Our key contributions include:
A (2+ϵ)-approximation for all-pairs shortest paths in O(log2n/ϵ) rounds on unweighted undirected graphs. With a small additional additive factor, this also applies for weighted graphs. This is the first sub-polynomial constant-factor approximation for APSP in this model.
A (1+ϵ)-approximation for multi-source shortest paths from O(n−−√) sources in O(log2n/ϵ) rounds on weighted undirected graphs. This is the first sub-polynomial algorithm obtaining this approximation for a set of sources of polynomial size.
Our main techniques are new distance tools that are obtained via improved algorithms for sparse matrix multiplication, which we leverage to construct efficient hopsets and shortest paths. Furthermore, our techniques extend to additional distance problems for which we improve upon the state-of-the-art, including diameter approximation, and an exact single-source shortest paths algorithm for weighted undirected graphs in O~(n1/6) rounds.
AU - Censor-Hillel, Keren
AU - Dory, Michal
AU - Korhonen, Janne
AU - Leitersdorf, Dean
ID - 7939
JF - Distributed Computing
SN - 01782770
TI - Fast approximate shortest paths in the congested clique
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
ER -
TY - CHAP
AB - Expansion microscopy is a recently developed super-resolution imaging technique, which provides an alternative to optics-based methods such as deterministic approaches (e.g. STED) or stochastic approaches (e.g. PALM/STORM). The idea behind expansion microscopy is to embed the biological sample in a swellable gel, and then to expand it isotropically, thereby increasing the distance between the fluorophores. This approach breaks the diffraction barrier by simply separating the emission point-spread-functions of the fluorophores. The resolution attainable in expansion microscopy is thus directly dependent on the separation that can be achieved, i.e. on the expansion factor. The original implementation of the technique achieved an expansion factor of fourfold, for a resolution of 70–80 nm. The subsequently developed X10 method achieves an expansion factor of 10-fold, for a resolution of 25–30 nm. This technique can be implemented with minimal technical requirements on any standard fluorescence microscope, and is more easily applied for multi-color imaging than either deterministic or stochastic super-resolution approaches. This renders X10 expansion microscopy a highly promising tool for new biological discoveries, as discussed here, and as demonstrated by several recent applications.
AU - Truckenbrodt, Sven M
AU - Rizzoli, Silvio O.
ID - 7941
SN - 0091679X
T2 - Methods in Cell Biology
TI - Simple multi-color super-resolution by X10 microscopy
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
ER -
TY - THES
AB - This thesis considers two examples of reconfiguration problems: flipping edges in edge-labelled triangulations of planar point sets and swapping labelled tokens placed on vertices of a graph. In both cases the studied structures – all the triangulations of a given point set or all token placements on a given graph – can be thought of as vertices of the so-called reconfiguration graph, in which two vertices are adjacent if the corresponding structures differ by a single elementary operation – by a flip of a diagonal in a triangulation or by a swap of tokens on adjacent vertices, respectively. We study the reconfiguration of one instance of a structure into another via (shortest) paths in the reconfiguration graph.
For triangulations of point sets in which each edge has a unique label and a flip transfers the label from the removed edge to the new edge, we prove a polynomial-time testable condition, called the Orbit Theorem, that characterizes when two triangulations of the same point set lie in the same connected component of the reconfiguration graph. The condition was first conjectured by Bose, Lubiw, Pathak and Verdonschot. We additionally provide a polynomial time algorithm that computes a reconfiguring flip sequence, if it exists. Our proof of the Orbit Theorem uses topological properties of a certain high-dimensional cell complex that has the usual reconfiguration graph as its 1-skeleton.
In the context of token swapping on a tree graph, we make partial progress on the problem of finding shortest reconfiguration sequences. We disprove the so-called Happy Leaf Conjecture and demonstrate the importance of swapping tokens that are already placed at the correct vertices. We also prove that a generalization of the problem to weighted coloured token swapping is NP-hard on trees but solvable in polynomial time on paths and stars.
AU - Masárová, Zuzana
ID - 7944
KW - reconfiguration
KW - reconfiguration graph
KW - triangulations
KW - flip
KW - constrained triangulations
KW - shellability
KW - piecewise-linear balls
KW - token swapping
KW - trees
KW - coloured weighted token swapping
SN - 978-3-99078-005-3
TI - Reconfiguration problems
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
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
ER -
TY - JOUR
AB - Peptides derived from non-functional precursors play important roles in various developmental processes, but also in (a)biotic stress signaling. Our (phospho)proteome-wide analyses of C-terminally encoded peptide 5 (CEP5)-mediated changes revealed an impact on abiotic stress-related processes. Drought has a dramatic impact on plant growth, development and reproduction, and the plant hormone auxin plays a role in drought responses. Our genetic, physiological, biochemical and pharmacological results demonstrated that CEP5-mediated signaling is relevant for osmotic and drought stress tolerance in Arabidopsis, and that CEP5 specifically counteracts auxin effects. Specifically, we found that CEP5 signaling stabilizes AUX/IAA transcriptional repressors, suggesting the existence of a novel peptide-dependent control mechanism that tunes auxin signaling. These observations align with the recently described role of AUX/IAAs in stress tolerance and provide a novel role for CEP5 in osmotic and drought stress tolerance.
AU - Smith, S
AU - Zhu, S
AU - Joos, L
AU - Roberts, I
AU - Nikonorova, N
AU - Vu, LD
AU - Stes, E
AU - Cho, H
AU - Larrieu, A
AU - Xuan, W
AU - Goodall, B
AU - van de Cotte, B
AU - Waite, JM
AU - Rigal, A
AU - R Harborough, SR
AU - Persiau, G
AU - Vanneste, S
AU - Kirschner, GK
AU - Vandermarliere, E
AU - Martens, L
AU - Stahl, Y
AU - Audenaert, D
AU - Friml, Jiří
AU - Felix, G
AU - Simon, R
AU - Bennett, M
AU - Bishopp, A
AU - De Jaeger, G
AU - Ljung, K
AU - Kepinski, S
AU - Robert, S
AU - Nemhauser, J
AU - Hwang, I
AU - Gevaert, K
AU - Beeckman, T
AU - De Smet, I
ID - 7949
IS - 8
JF - Molecular & Cellular Proteomics
SN - 1535-9476
TI - The CEP5 peptide promotes abiotic stress tolerance, as revealed by quantitative proteomics, and attenuates the AUX/IAA equilibrium in Arabidopsis
VL - 19
ER -
TY - CONF
AB - Isomanifolds are the generalization of isosurfaces to arbitrary dimension and codimension, i.e. manifolds defined as the zero set of some multivariate vector-valued smooth function f: ℝ^d → ℝ^(d-n). A natural (and efficient) way to approximate an isomanifold is to consider its Piecewise-Linear (PL) approximation based on a triangulation 𝒯 of the ambient space ℝ^d. In this paper, we give conditions under which the PL-approximation of an isomanifold is topologically equivalent to the isomanifold. The conditions are easy to satisfy in the sense that they can always be met by taking a sufficiently fine triangulation 𝒯. This contrasts with previous results on the triangulation of manifolds where, in arbitrary dimensions, delicate perturbations are needed to guarantee topological correctness, which leads to strong limitations in practice. We further give a bound on the Fréchet distance between the original isomanifold and its PL-approximation. Finally we show analogous results for the PL-approximation of an isomanifold with boundary.
AU - Boissonnat, Jean-Daniel
AU - Wintraecken, Mathijs
ID - 7952
SN - 1868-8969
T2 - 36th International Symposium on Computational Geometry
TI - The topological correctness of PL-approximations of isomanifolds
VL - 164
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 - We prove edge universality for a general class of correlated real symmetric or complex Hermitian Wigner matrices with arbitrary expectation. Our theorem also applies to internal edges of the self-consistent density of states. In particular, we establish a strong form of band rigidity which excludes mismatches between location and label of eigenvalues close to internal edges in these general models.
AU - Alt, Johannes
AU - Erdös, László
AU - Krüger, Torben H
AU - Schröder, Dominik J
ID - 6184
IS - 2
JF - Annals of Probability
TI - Correlated random matrices: Band rigidity and edge universality
VL - 48
ER -
TY - JOUR
AB - For complex Wigner-type matrices, i.e. Hermitian random matrices with independent, not necessarily identically distributed entries above the diagonal, we show that at any cusp singularity of the limiting eigenvalue distribution the local eigenvalue statistics are universal and form a Pearcey process. Since the density of states typically exhibits only square root or cubic root cusp singularities, our work complements previous results on the bulk and edge universality and it thus completes the resolution of the Wigner–Dyson–Mehta universality conjecture for the last remaining universality type in the complex Hermitian class. Our analysis holds not only for exact cusps, but approximate cusps as well, where an extended Pearcey process emerges. As a main technical ingredient we prove an optimal local law at the cusp for both symmetry classes. This result is also the key input in the companion paper (Cipolloni et al. in Pure Appl Anal, 2018. arXiv:1811.04055) where the cusp universality for real symmetric Wigner-type matrices is proven. The novel cusp fluctuation mechanism is also essential for the recent results on the spectral radius of non-Hermitian random matrices (Alt et al. in Spectral radius of random matrices with independent entries, 2019. arXiv:1907.13631), and the non-Hermitian edge universality (Cipolloni et al. in Edge universality for non-Hermitian random matrices, 2019. arXiv:1908.00969).
AU - Erdös, László
AU - Krüger, Torben H
AU - Schröder, Dominik J
ID - 6185
JF - Communications in Mathematical Physics
SN - 0010-3616
TI - Cusp universality for random matrices I: Local law and the complex hermitian case
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TY - JOUR
AB - We study dynamical optimal transport metrics between density matricesassociated to symmetric Dirichlet forms on finite-dimensional C∗-algebras. Our settingcovers arbitrary skew-derivations and it provides a unified framework that simultaneously generalizes recently constructed transport metrics for Markov chains, Lindblad equations, and the Fermi Ornstein–Uhlenbeck semigroup. We develop a non-nommutative differential calculus that allows us to obtain non-commutative Ricci curvature bounds, logarithmic Sobolev inequalities, transport-entropy inequalities, andspectral gap estimates.
AU - Carlen, Eric A.
AU - Maas, Jan
ID - 6358
IS - 2
JF - Journal of Statistical Physics
SN - 00224715
TI - Non-commutative calculus, optimal transport and functional inequalities in dissipative quantum systems
VL - 178
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TY - JOUR
AB - This paper presents two algorithms. The first decides the existence of a pointed homotopy between given simplicial maps 𝑓,𝑔:𝑋→𝑌, and the second computes the group [𝛴𝑋,𝑌]∗ of pointed homotopy classes of maps from a suspension; in both cases, the target Y is assumed simply connected. More generally, these algorithms work relative to 𝐴⊆𝑋.
AU - Filakovský, Marek
AU - Vokřínek, Lukas
ID - 6563
JF - Foundations of Computational Mathematics
SN - 16153375
TI - Are two given maps homotopic? An algorithmic viewpoint
VL - 20
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TY - JOUR
AB - We consider the monotone variational inequality problem in a Hilbert space and describe a projection-type method with inertial terms under the following properties: (a) The method generates a strongly convergent iteration sequence; (b) The method requires, at each iteration, only one projection onto the feasible set and two evaluations of the operator; (c) The method is designed for variational inequality for which the underline operator is monotone and uniformly continuous; (d) The method includes an inertial term. The latter is also shown to speed up the convergence in our numerical results. A comparison with some related methods is given and indicates that the new method is promising.
AU - Shehu, Yekini
AU - Li, Xiao-Huan
AU - Dong, Qiao-Li
ID - 6593
JF - Numerical Algorithms
SN - 1017-1398
TI - An efficient projection-type method for monotone variational inequalities in Hilbert spaces
VL - 84
ER -