@article{7567, abstract = {Coxeter triangulations are triangulations of Euclidean space based on a single simplex. By this we mean that given an individual simplex we can recover the entire triangulation of Euclidean space by inductively reflecting in the faces of the simplex. In this paper we establish that the quality of the simplices in all Coxeter triangulations is O(1/d−−√) of the quality of regular simplex. We further investigate the Delaunay property for these triangulations. Moreover, we consider an extension of the Delaunay property, namely protection, which is a measure of non-degeneracy of a Delaunay triangulation. In particular, one family of Coxeter triangulations achieves the protection O(1/d2). We conjecture that both bounds are optimal for triangulations in Euclidean space.}, author = {Choudhary, Aruni and Kachanovich, Siargey and Wintraecken, Mathijs}, issn = {1661-8289}, journal = {Mathematics in Computer Science}, pages = {141--176}, publisher = {Springer Nature}, title = {{Coxeter triangulations have good quality}}, doi = {10.1007/s11786-020-00461-5}, volume = {14}, year = {2020}, } @article{7570, abstract = {The relaxation of few-body quantum systems can strongly depend on the initial state when the system’s semiclassical phase space is mixed; i.e., regions of chaotic motion coexist with regular islands. In recent years, there has been much effort to understand the process of thermalization in strongly interacting quantum systems that often lack an obvious semiclassical limit. The time-dependent variational principle (TDVP) allows one to systematically derive an effective classical (nonlinear) dynamical system by projecting unitary many-body dynamics onto a manifold of weakly entangled variational states. We demonstrate that such dynamical systems generally possess mixed phase space. When TDVP errors are small, the mixed phase space leaves a footprint on the exact dynamics of the quantum model. For example, when the system is initialized in a state belonging to a stable periodic orbit or the surrounding regular region, it exhibits persistent many-body quantum revivals. As a proof of principle, we identify new types of “quantum many-body scars,” i.e., initial states that lead to long-time oscillations in a model of interacting Rydberg atoms in one and two dimensions. Intriguingly, the initial states that give rise to most robust revivals are typically entangled states. On the other hand, even when TDVP errors are large, as in the thermalizing tilted-field Ising model, initializing the system in a regular region of phase space leads to a surprising slowdown of thermalization. Our work establishes TDVP as a method for identifying interacting quantum systems with anomalous dynamics in arbitrary dimensions. Moreover, the mixed phase space classical variational equations allow one to find slowly thermalizing initial conditions in interacting models. Our results shed light on a link between classical and quantum chaos, pointing toward possible extensions of the classical Kolmogorov-Arnold-Moser theorem to quantum systems.}, author = {Michailidis, Alexios and Turner, C. J. and Papić, Z. and Abanin, D. A. and Serbyn, Maksym}, issn = {2160-3308}, journal = {Physical Review X}, number = {1}, publisher = {American Physical Society}, title = {{Slow quantum thermalization and many-body revivals from mixed phase space}}, doi = {10.1103/physrevx.10.011055}, volume = {10}, year = {2020}, } @inbook{7591, abstract = {Rechargeable Li–O2 batteries have gathered enormous attention in the research community for having amongst the highest theoretical energy storage. Realizing the promise, even in part, in practice could produce a device that stores significantly more energy than other rechargeable batteries. Fundamental understanding of the reaction mechanisms is now realized to be key to overcome many challenges. We give a critical overview of the current understanding of the chemistry underpinning the Li–O2 cell with focus on the cathode and give a perspective on the most important research needs. Since performance and reversibility are often grossly misunderstood, we put emphasis on realistic performances to be achieved by Li–O2 cells and on means to identify reversibility. Parasitic chemistry is the foremost barrier for reversible cycling and now realized to be predominantly caused by singlet oxygen rather than by the previously thought superoxide or peroxide. This finding profoundly affects any other area of research from reaction mechanisms, to electrolytes and catalysts and dominates future research needs.}, author = {Petit, Yann K. and Mourad, Eléonore and Freunberger, Stefan Alexander}, booktitle = {Encyclopedia of Electrochemistry}, isbn = {9783527302505}, pages = {1--42}, publisher = {Wiley}, title = {{Lithium–Oxygen batteries}}, doi = {10.1002/9783527610426.bard110017}, year = {2020}, } @article{7593, abstract = {Heterozygous loss of human PAFAH1B1 (coding for LIS1) results in the disruption of neurogenesis and neuronal migration via dysregulation of microtubule (MT) stability and dynein motor function/localization that alters mitotic spindle orientation, chromosomal segregation, and nuclear migration. Recently, human induced pluripotent stem cell (iPSC) models revealed an important role for LIS1 in controlling the length of terminal cell divisions of outer radial glial (oRG) progenitors, suggesting cellular functions of LIS1 in regulating neural progenitor cell (NPC) daughter cell separation. Here we examined the late mitotic stages NPCs in vivo and mouse embryonic fibroblasts (MEFs) in vitro from Pafah1b1-deficient mutants. Pafah1b1-deficient neocortical NPCs and MEFs similarly exhibited cleavage plane displacement with mislocalization of furrow-associated markers, associated with actomyosin dysfunction and cell membrane hyper-contractility. Thus, it suggests LIS1 acts as a key molecular link connecting MTs/dynein and actomyosin, ensuring that cell membrane contractility is tightly controlled to execute proper daughter cell separation.}, author = {Moon, Hyang Mi and Hippenmeyer, Simon and Luo, Liqun and Wynshaw-Boris, Anthony}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility}}, doi = {10.7554/elife.51512}, volume = {9}, year = {2020}, } @article{7594, abstract = {The concept of the entanglement between spin and orbital degrees of freedom plays a crucial role in our understanding of various phases and exotic ground states in a broad class of materials, including orbitally ordered materials and spin liquids. We investigate how the spin-orbital entanglement in a Mott insulator depends on the value of the spin-orbit coupling of the relativistic origin. To this end, we numerically diagonalize a one-dimensional spin-orbital model with Kugel-Khomskii exchange interactions between spins and orbitals on different sites supplemented by the on-site spin-orbit coupling. In the regime of small spin-orbit coupling with regard to the spin-orbital exchange, the ground state to a large extent resembles the one obtained in the limit of vanishing spin-orbit coupling. On the other hand, for large spin-orbit coupling the ground state can, depending on the model parameters, either still show negligible spin-orbital entanglement or evolve to a highly spin-orbitally-entangled phase with completely distinct properties that are described by an effective XXZ model. The presented results suggest that (i) the spin-orbital entanglement may be induced by large on-site spin-orbit coupling, as found in the 5d transition metal oxides, such as the iridates; (ii) for Mott insulators with weak spin-orbit coupling of Ising type, such as, e.g., the alkali hyperoxides, the effects of the spin-orbit coupling on the ground state can, in the first order of perturbation theory, be neglected.}, author = {Gotfryd, Dorota and Paerschke, Ekaterina and Chaloupka, Jiri and Oles, Andrzej M. and Wohlfeld, Krzysztof}, journal = {Physical Review Research}, number = {1}, publisher = {American Physical Society}, title = {{How spin-orbital entanglement depends on the spin-orbit coupling in a Mott insulator}}, doi = {10.1103/PhysRevResearch.2.013353}, volume = {2}, year = {2020}, } @unpublished{7601, abstract = {Plasmodesmata (PD) are crucial structures for intercellular communication in multicellular plants with remorins being their crucial plant-specific structural and functional constituents. The PD biogenesis is an intriguing but poorly understood process. By expressing an Arabidopsis remorin protein in mammalian cells, we have reconstituted a PD-like filamentous structure, termed remorin filament (RF), connecting neighboring cells physically and physiologically. Notably, RFs are capable of transporting macromolecules intercellularly, in a way similar to plant PD. With further super-resolution microscopic analysis and biochemical characterization, we found that RFs are also composed of actin filaments, forming the core skeleton structure, aligned with the remorin protein. This unique heterologous filamentous structure might explain the molecular mechanism for remorin function as well as PD construction. Furthermore, remorin protein exhibits a specific distribution manner in the plasma membrane in mammalian cells, representing a lipid nanodomain, depending on its lipid modification status. Our studies not only provide crucial insights into the mechanism of PD biogenesis, but also uncovers unsuspected fundamental mechanistic and evolutionary links between intercellular communication systems of plants and animals.}, author = {Wei, Zhuang and Tan, Shutang and Liu, Tao and Wu, Yuan and Lei, Ji-Gang and Chen, ZhengJun and Friml, Jiří and Xue, Hong-Wei and Liao, Kan}, booktitle = {bioRxiv}, pages = {22}, publisher = {Cold Spring Harbor Laboratory}, title = {{Plasmodesmata-like intercellular connections by plant remorin in animal cells}}, doi = {10.1101/791137}, year = {2020}, } @inproceedings{7605, abstract = {Union-Find (or Disjoint-Set Union) is one of the fundamental problems in computer science; it has been well-studied from both theoretical and practical perspectives in the sequential case. Recently, there has been mounting interest in analyzing this problem in the concurrent scenario, and several asymptotically-efficient algorithms have been proposed. Yet, to date, there is very little known about the practical performance of concurrent Union-Find. This work addresses this gap. We evaluate and analyze the performance of several concurrent Union-Find algorithms and optimization strategies across a wide range of platforms (Intel, AMD, and ARM) and workloads (social, random, and road networks, as well as integrations into more complex algorithms). We first observe that, due to the limited computational cost, the number of induced cache misses is the critical determining factor for the performance of existing algorithms. We introduce new techniques to reduce this cost by storing node priorities implicitly and by using plain reads and writes in a way that does not affect the correctness of the algorithms. Finally, we show that Union-Find implementations are an interesting application for Transactional Memory (TM): one of the fastest algorithm variants we discovered is a sequential one that uses coarse-grained locking with the lock elision optimization to reduce synchronization cost and increase scalability. }, author = {Alistarh, Dan-Adrian and Fedorov, Alexander and Koval, Nikita}, booktitle = {23rd International Conference on Principles of Distributed Systems}, isbn = {9783959771337}, issn = {1868-8969}, location = {Neuchatal, Switzerland}, pages = {15:1--15:16}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{In search of the fastest concurrent union-find algorithm}}, doi = {10.4230/LIPIcs.OPODIS.2019.15}, volume = {153}, year = {2020}, } @article{7611, abstract = {We consider a system of N bosons in the limit N→∞, interacting through singular potentials. For initial data exhibiting Bose–Einstein condensation, the many-body time evolution is well approximated through a quadratic fluctuation dynamics around a cubic nonlinear Schrödinger equation of the condensate wave function. We show that these fluctuations satisfy a (multi-variate) central limit theorem.}, author = {Rademacher, Simone Anna Elvira}, issn = {1573-0530}, journal = {Letters in Mathematical Physics}, pages = {2143--2174}, publisher = {Springer Nature}, title = {{Central limit theorem for Bose gases interacting through singular potentials}}, doi = {10.1007/s11005-020-01286-w}, volume = {110}, year = {2020}, } @article{7618, abstract = {This short note aims to study quantum Hellinger distances investigated recently by Bhatia et al. (Lett Math Phys 109:1777–1804, 2019) with a particular emphasis on barycenters. We introduce the family of generalized quantum Hellinger divergences that are of the form ϕ(A,B)=Tr((1−c)A+cB−AσB), where σ is an arbitrary Kubo–Ando mean, and c∈(0,1) is the weight of σ. We note that these divergences belong to the family of maximal quantum f-divergences, and hence are jointly convex, and satisfy the data processing inequality. We derive a characterization of the barycenter of finitely many positive definite operators for these generalized quantum Hellinger divergences. We note that the characterization of the barycenter as the weighted multivariate 1/2-power mean, that was claimed in Bhatia et al. (2019), is true in the case of commuting operators, but it is not correct in the general case. }, author = {Pitrik, Jozsef and Virosztek, Daniel}, issn = {1573-0530}, journal = {Letters in Mathematical Physics}, number = {8}, pages = {2039--2052}, publisher = {Springer Nature}, title = {{Quantum Hellinger distances revisited}}, doi = {10.1007/s11005-020-01282-0}, volume = {110}, year = {2020}, } @article{7619, abstract = {Cell polarity is a fundamental feature of all multicellular organisms. In plants, prominent cell polarity markers are PIN auxin transporters crucial for plant development. To identify novel components involved in cell polarity establishment and maintenance, we carried out a forward genetic screening with PIN2:PIN1-HA;pin2 Arabidopsis plants, which ectopically express predominantly basally localized PIN1 in the root epidermal cells leading to agravitropic root growth. From the screen, we identified the regulator of PIN polarity 12 (repp12) mutation, which restored gravitropic root growth and caused PIN1-HA polarity switch from basal to apical side of root epidermal cells. Complementation experiments established the repp12 causative mutation as an amino acid substitution in Aminophospholipid ATPase3 (ALA3), a phospholipid flippase with predicted function in vesicle formation. ala3 T-DNA mutants show defects in many auxin-regulated processes, in asymmetric auxin distribution and in PIN trafficking. Analysis of quintuple and sextuple mutants confirmed a crucial role of ALA proteins in regulating plant development and in PIN trafficking and polarity. Genetic and physical interaction studies revealed that ALA3 functions together with GNOM and BIG3 ARF GEFs. Taken together, our results identified ALA3 flippase as an important interactor and regulator of ARF GEF functioning in PIN polarity, trafficking and auxin-mediated development.}, author = {Zhang, Xixi and Adamowski, Maciek and Marhavá, Petra and Tan, Shutang and Zhang, Yuzhou and Rodriguez Solovey, Lesia and Zwiewka, Marta and Pukyšová, Vendula and Sánchez, Adrià Sans and Raxwal, Vivek Kumar and Hardtke, Christian S. and Nodzynski, Tomasz and Friml, Jiří}, issn = {1532-298X}, journal = {The Plant Cell}, number = {5}, pages = {1644--1664}, publisher = {American Society of Plant Biologists}, title = {{Arabidopsis flippases cooperate with ARF GTPase exchange factors to regulate the trafficking and polarity of PIN auxin transporters}}, doi = {10.1105/tpc.19.00869}, volume = {32}, year = {2020}, } @article{7634, abstract = {Assemblies of colloidal semiconductor nanocrystals (NCs) in the form of thin solid films leverage the size-dependent quantum confinement properties and the wet chemical methods vital for the development of the emerging solution-processable electronics, photonics, and optoelectronics technologies. The ability to control the charge carrier transport in the colloidal NC assemblies is fundamental for altering their electronic and optical properties for the desired applications. Here we demonstrate a strategy to render the solids of narrow-bandgap NC assemblies exclusively electron-transporting by creating a type-II heterojunction via shelling. Electronic transport of molecularly cross-linked PbTe@PbS core@shell NC assemblies is measured using both a conventional solid gate transistor and an electric-double-layer transistor, as well as compared with those of core-only PbTe NCs. In contrast to the ambipolar characteristics demonstrated by many narrow-bandgap NCs, the core@shell NCs exhibit exclusive n-type transport, i.e., drastically suppressed contribution of holes to the overall transport. The PbS shell that forms a type-II heterojunction assists the selective carrier transport by heavy doping of electrons into the PbTe-core conduction level and simultaneously strongly localizes the holes within the NC core valence level. This strongly enhanced n-type transport makes these core@shell NCs suitable for applications where ambipolar characteristics should be actively suppressed, in particular, for thermoelectric and electron-transporting layers in photovoltaic devices.}, author = {Miranti, Retno and Shin, Daiki and Septianto, Ricky Dwi and Ibáñez, Maria and Kovalenko, Maksym V. and Matsushita, Nobuhiro and Iwasa, Yoshihiro and Bisri, Satria Zulkarnaen}, issn = {1936-086X}, journal = {ACS Nano}, number = {3}, pages = {3242--3250}, publisher = {American Chemical Society}, title = {{Exclusive electron transport in Core@Shell PbTe@PbS colloidal semiconductor nanocrystal assemblies}}, doi = {10.1021/acsnano.9b08687}, volume = {14}, year = {2020}, } @inproceedings{7635, abstract = {Concurrent programming can be notoriously complex and error-prone. Programming bugs can arise from a variety of sources, such as operation re-reordering, or incomplete understanding of the memory model. A variety of formal and model checking methods have been developed to address this fundamental difficulty. While technically interesting, existing academic methods are still hard to apply to the large codebases typical of industrial deployments, which limits their practical impact.}, author = {Koval, Nikita and Sokolova, Mariia and Fedorov, Alexander and Alistarh, Dan-Adrian and Tsitelov, Dmitry}, booktitle = {Proceedings of the ACM SIGPLAN Symposium on Principles and Practice of Parallel Programming}, isbn = {9781450368186}, location = {San Diego, CA, United States}, pages = {423--424}, publisher = {Association for Computing Machinery}, title = {{Testing concurrency on the JVM with Lincheck}}, doi = {10.1145/3332466.3374503}, year = {2020}, } @inproceedings{7636, abstract = {Balanced search trees typically use key comparisons to guide their operations, and achieve logarithmic running time. By relying on numerical properties of the keys, interpolation search achieves lower search complexity and better performance. Although interpolation-based data structures were investigated in the past, their non-blocking concurrent variants have received very little attention so far. In this paper, we propose the first non-blocking implementation of the classic interpolation search tree (IST) data structure. For arbitrary key distributions, the data structure ensures worst-case O(log n + p) amortized time for search, insertion and deletion traversals. When the input key distributions are smooth, lookups run in expected O(log log n + p) time, and insertion and deletion run in expected amortized O(log log n + p) time, where p is a bound on the number of threads. To improve the scalability of concurrent insertion and deletion, we propose a novel parallel rebuilding technique, which should be of independent interest. We evaluate whether the theoretical improvements translate to practice by implementing the concurrent interpolation search tree, and benchmarking it on uniform and nonuniform key distributions, for dataset sizes in the millions to billions of keys. Relative to the state-of-the-art concurrent data structures, the concurrent interpolation search tree achieves performance improvements of up to 15% under high update rates, and of up to 50% under moderate update rates. Further, ISTs exhibit up to 2X less cache-misses, and consume 1.2 -- 2.6X less memory compared to the next best alternative on typical dataset sizes. We find that the results are surprisingly robust to distributional skew, which suggests that our data structure can be a promising alternative to classic concurrent search structures.}, author = {Brown, Trevor A and Prokopec, Aleksandar and Alistarh, Dan-Adrian}, booktitle = {Proceedings of the ACM SIGPLAN Symposium on Principles and Practice of Parallel Programming}, isbn = {9781450368186}, location = {San Diego, CA, United States}, pages = {276--291}, publisher = {Association for Computing Machinery}, title = {{Non-blocking interpolation search trees with doubly-logarithmic running time}}, doi = {10.1145/3332466.3374542}, year = {2020}, } @article{7646, abstract = {In plant cells, environmental stressors promote changes in connectivity between the cortical ER and the PM. Although this process is tightly regulated in space and time, the molecular signals and structural components mediating these changes in inter-organelle communication are only starting to be characterized. In this report, we confirm the presence of a putative tethering complex containing the synaptotagmins 1 and 5 (SYT1 and SYT5) and the Ca2+ and lipid binding protein 1 (CLB1/SYT7). This complex is enriched at ER-PM contact sites (EPCS), have slow responses to changes in extracellular Ca2+, and display severe cytoskeleton-dependent rearrangements in response to the trivalent lanthanum (La3+) and gadolinium (Gd3+) rare earth elements (REEs). Although REEs are generally used as non-selective cation channel blockers at the PM, here we show that the slow internalization of REEs into the cytosol underlies the activation of the Ca2+/Calmodulin intracellular signaling, the accumulation of phosphatidylinositol-4-phosphate (PI4P) at the PM, and the cytoskeleton-dependent rearrangement of the SYT1/SYT5 EPCS complexes. We propose that the observed EPCS rearrangements act as a slow adaptive response to sustained stress conditions, and that this process involves the accumulation of stress-specific phosphoinositides species at the PM.}, author = {Lee, E and Vila Nova Santana, B and Samuels, E and Benitez-Fuente, F and Corsi, E and Botella, MA and Perez-Sancho, J and Vanneste, S and Friml, Jiří and Macho, A and Alves Azevedo, A and Rosado, A}, issn = {1460-2431}, journal = {Journal of Experimental Botany}, number = {14}, pages = {3986–3998}, publisher = {Oxford University Press}, title = {{Rare earth elements induce cytoskeleton-dependent and PI4P-associated rearrangement of SYT1/SYT5 ER-PM contact site complexes in Arabidopsis}}, doi = {10.1093/jxb/eraa138}, volume = {71}, year = {2020}, } @article{7650, abstract = {We consider a dilute, homogeneous Bose gas at positive temperature. The system is investigated in the Gross–Pitaevskii limit, where the scattering length a is so small that the interaction energy is of the same order of magnitude as the spectral gap of the Laplacian, and for temperatures that are comparable to the critical temperature of the ideal gas. We show that the difference between the specific free energy of the interacting system and the one of the ideal gas is to leading order given by 4πa(2ϱ2−ϱ20). Here ϱ denotes the density of the system and ϱ0 is the expected condensate density of the ideal gas. Additionally, we show that the one-particle density matrix of any approximate minimizer of the Gibbs free energy functional is to leading order given by the one of the ideal gas. This in particular proves Bose–Einstein condensation with critical temperature given by the one of the ideal gas to leading order. One key ingredient of our proof is a novel use of the Gibbs variational principle that goes hand in hand with the c-number substitution.}, author = {Deuchert, Andreas and Seiringer, Robert}, issn = {1432-0673}, journal = {Archive for Rational Mechanics and Analysis}, number = {6}, pages = {1217--1271}, publisher = {Springer Nature}, title = {{Gross-Pitaevskii limit of a homogeneous Bose gas at positive temperature}}, doi = {10.1007/s00205-020-01489-4}, volume = {236}, year = {2020}, } @article{7651, abstract = {The growth of snail shells can be described by simple mathematical rules. Variation in a few parameters can explain much of the diversity of shell shapes seen in nature. However, empirical studies of gastropod shell shape variation typically use geometric morphometric approaches, which do not capture this growth pattern. We have developed a way to infer a set of developmentally descriptive shape parameters based on three-dimensional logarithmic helicospiral growth and using landmarks from two-dimensional shell images as input. We demonstrate the utility of this approach, and compare it to the geometric morphometric approach, using a large set of Littorina saxatilis shells in which locally adapted populations differ in shape. Our method can be modified easily to make it applicable to a wide range of shell forms, which would allow for investigations of the similarities and differences between and within many different species of gastropods.}, author = {Larsson, J. and Westram, Anja M and Bengmark, S. and Lundh, T. and Butlin, R. K.}, issn = {1742-5662}, journal = {Journal of The Royal Society Interface}, number = {163}, publisher = {The Royal Society}, title = {{A developmentally descriptive method for quantifying shape in gastropod shells}}, doi = {10.1098/rsif.2019.0721}, volume = {17}, year = {2020}, } @misc{9878, author = {Gupta, Chitrak and Khaniya, Umesh and Chan, Chun Kit and Dehez, Francois and Shekhar, Mrinal and Gunner, M.R. and Sazanov, Leonid A and Chipot, Christophe and Singharoy, Abhishek}, publisher = {American Chemical Society}, title = {{Movies}}, doi = {10.1021/jacs.9b13450.s002}, year = {2020}, } @misc{9885, abstract = {Data obtained from the fine-grained simulations used in Figures 2-5, data obtained from the coarse-grained numerical calculations used in Figure 6, and a sample script for the fine-grained simulation as a Jupyter notebook (ZIP)}, author = {Ucar, Mehmet C and Lipowsky, Reinhard}, publisher = {American Chemical Society }, title = {{MURL_Dataz}}, doi = {10.1021/acs.nanolett.9b04445.s002}, year = {2020}, } @article{7687, abstract = {A working group, which was established within the Network of Repository Managers (RepManNet), has dealt with common certifications for repositories. In addition, current requirements of the research funding agencies FWF and EU were also taken into account. The Core Trust Seal was examined in more detail. For this purpose, a questionnaire was sent to those organizations that are already certified with CTS in Austria. The answers were summarized and evaluated anonymously. It is recommended to go for a repository certification. Moreover, the development of a DINI certificate in Austria is strongly suggested.}, author = {Ernst, Doris and Novotny, Gertraud and Schönher, Eva Maria}, issn = {1022-2588}, journal = {Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen und Bibliothekare}, number = {1}, pages = {46--59}, publisher = {Vereinigung Österreichischer Bibliothekarinnen und Bibliothekare}, title = {{(Core Trust) Seal your repository!}}, doi = {10.31263/voebm.v73i1.3491}, volume = {73}, year = {2020}, } @article{7487, abstract = {Glutaminase (GA) catalyzes the first step in mitochondrial glutaminolysis playing a key role in cancer metabolic reprogramming. Humans express two types of GA isoforms: GLS and GLS2. GLS isozymes have been consistently related to cell proliferation, but the role of GLS2 in cancer remains poorly understood. GLS2 is repressed in many tumor cells and a better understanding of its function in tumorigenesis may further the development of new therapeutic approaches. We analyzed GLS2 expression in HCC, GBM and neuroblastoma cells, as well as in monkey COS-7 cells. We studied GLS2 expression after induction of differentiation with phorbol ester (PMA) and transduction with the full-length cDNA of GLS2. In parallel, we investigated cell cycle progression and levels of p53, p21 and c-Myc proteins. Using the baculovirus system, human GLS2 protein was overexpressed, purified and analyzed for posttranslational modifications employing a proteomics LC-MS/MS platform. We have demonstrated a dual targeting of GLS2 in human cancer cells. Immunocytochemistry and subcellular fractionation gave consistent results demonstrating nuclear and mitochondrial locations, with the latter being predominant. Nuclear targeting was confirmed in cancer cells overexpressing c-Myc- and GFP-tagged GLS2 proteins. We assessed the subnuclear location finding a widespread distribution of GLS2 in the nucleoplasm without clear overlapping with specific nuclear substructures. GLS2 expression and nuclear accrual notably increased by treatment of SH-SY5Y cells with PMA and it correlated with cell cycle arrest at G2/M, upregulation of tumor suppressor p53 and p21 protein. A similar response was obtained by overexpression of GLS2 in T98G glioma cells, including downregulation of oncogene c-Myc. Furthermore, human GLS2 was identified as being hypusinated by MS analysis, a posttranslational modification which may be relevant for its nuclear targeting and/or function. Our studies provide evidence for a tumor suppressor role of GLS2 in certain types of cancer. The data imply that GLS2 can be regarded as a highly mobile and multilocalizing protein translocated to both mitochondria and nuclei. Upregulation of GLS2 in cancer cells induced an antiproliferative response with cell cycle arrest at the G2/M phase.}, author = {López De La Oliva, Amada R. and Campos-Sandoval, José A. and Gómez-García, María C. and Cardona, Carolina and Martín-Rufián, Mercedes and Sialana, Fernando J. and Castilla, Laura and Bae, Narkhyun and Lobo, Carolina and Peñalver, Ana and García-Frutos, Marina and Carro, David and Enrique, Victoria and Paz, José C. and Mirmira, Raghavendra G. and Gutiérrez, Antonia and Alonso, Francisco J. and Segura, Juan A. and Matés, José M. and Lubec, Gert and Márquez, Javier}, issn = {2045-2322}, journal = {Scientific reports}, number = {1}, publisher = {Springer Nature}, title = {{Nuclear translocation of glutaminase GLS2 in human cancer cells associates with proliferation arrest and differentiation}}, doi = {10.1038/s41598-020-58264-4}, volume = {10}, year = {2020}, }