@article{11122, abstract = {Nuclear pore complexes (NPCs) are large multiprotein assemblies that allow traffic between the cytoplasm and the nucleus. During mitosis in higher eukaryotes, the Nuclear Envelope (NE) breaks down and NPCs disassemble. How NPCs reassemble and incorporate into the NE upon mitotic exit is poorly understood. We demonstrate a function for the conserved Nup107-160 complex in this process. Partial in vivo depletion of Nup133 or Nup107 via RNAi in HeLa cells resulted in reduced levels of multiple nucleoporins and decreased NPC density in the NE. Immunodepletion of the entire Nup107-160 complex from in vitro nuclear assembly reactions produced nuclei with a continuous NE but no NPCs. This phenotype was reversible only if Nup107-160 complex was readded before closed NE formation. Depletion also prevented association of FG-repeat nucleoporins with chromatin. We propose a stepwise model in which postmitotic NPC assembly initiates on chromatin via early recruitment of the Nup107-160 complex.}, author = {Walther, Tobias C. and Alves, Annabelle and Pickersgill, Helen and Loı̈odice, Isabelle and HETZER, Martin W and Galy, Vincent and Hülsmann, Bastian B. and Köcher, Thomas and Wilm, Matthias and Allen, Terry and Mattaj, Iain W. and Doye, Valérie}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {2}, pages = {195--206}, publisher = {Elsevier}, title = {{The conserved Nup107-160 complex is critical for nuclear pore complex assembly}}, doi = {10.1016/s0092-8674(03)00235-6}, volume = {113}, year = {2003}, } @article{11121, abstract = {In metazoa, the nuclear envelope breaks down and reforms during each cell cycle. Nuclear pore complexes (NPCs), which serve as channels for transport between the nucleus and cytoplasm1, assemble into the reforming nuclear envelope in a sequential process involving association of a subset of NPC proteins, nucleoporins, with chromatin followed by the formation of a closed nuclear envelope fenestrated by NPCs2,3,4,5,6,7. How chromatin recruitment of nucleoporins and NPC assembly are regulated is unknown. Here we demonstrate that RanGTP production is required to dissociate nucleoporins Nup107, Nup153 and Nup358 from Importin β, to target them to chromatin and to induce association between separate NPC subcomplexes. Additionally, either an excess of RanGTP or removal of Importin β induces formation of NPC-containing membrane structures—annulate lamellae—both in vitro in the absence of chromatin and in vivo. Annulate lamellae formation is strongly and specifically inhibited by an excess of Importin β. The data demonstrate that RanGTP triggers distinct steps of NPC assembly, and suggest a mechanism for the spatial restriction of NPC assembly to the surface of chromatin.}, author = {Walther, Tobias C. and Askjaer, Peter and Gentzel, Marc and Habermann, Anja and Griffiths, Gareth and Wilm, Matthias and Mattaj, Iain W. and HETZER, Martin W}, issn = {1476-4687}, journal = {Nature}, keywords = {Multidisciplinary}, number = {6949}, pages = {689--694}, publisher = {Springer Nature}, title = {{RanGTP mediates nuclear pore complex assembly}}, doi = {10.1038/nature01898}, volume = {424}, year = {2003}, } @article{11766, abstract = {This paper studies the multicast routing and admission control problem on unit-capacity tree and mesh topologies in the throughput model. The problem is a generalization of the edge-disjoint paths problem and is NP-hard both on trees and meshes. We study both the offline and the online version of the problem: In the offline setting, we give the first constant-factor approximation algorithm for trees, and an -factor approximation algorithm for meshes. In the online setting, we give the first polylogarithmic competitive online algorithm for tree and mesh topologies. No polylogarithmic-competitive algorithm is possible on general network topologies (Lower bounds for on-line graph problems with application to on-line circuits and optical routing, in: Proceedings of the 28th ACM Symposium on Theory of Computing, 1996, pp. 531–540) and there exists a polylogarithmic lower bound on the competitive ratio of any online algorithm on tree topologies (Making commitments in the face of uncertainity: how to pick a winner almost every time, in: Proceedings of the 28th Annual ACM Symposium on Theory of Computing, 1996, pp. 519–530). We prove the same lower bound for meshes.}, author = {Henzinger, Monika H and Leonardi, Stefano}, issn = {0022-0000}, journal = {Journal of Computer and System Sciences}, number = {3}, pages = {567--611}, publisher = {Elsevier}, title = {{Scheduling multicasts on unit-capacity trees and meshes}}, doi = {10.1016/s0022-0000(03)00043-6}, volume = {66}, year = {2003}, } @article{11764, abstract = {In this paper we consider the online ftp problem. The goal is to service a sequence of file transfer requests given bandwidth constraints of the underlying communication network. The main result of the paper is a technique that leads to algorithms that optimize several natural metrics, such as max-stretch, total flow time, max flow time, and total completion time. In particular, we show how to achieve optimum total flow time and optimum max-stretch if we increase the capacity of the underlying network by a logarithmic factor. We show that the resource augmentation is necessary by proving polynomial lower bounds on the max-stretch and total flow time for the case where online and offline algorithms are using same-capacity edges. Moreover, we also give polylogarithmic lower bounds on the resource augmentation factor necessary in order to keep the total flow time and max-stretch within a constant factor of optimum.}, author = {Goel, Ashish and Henzinger, Monika H and Plotkin, Serge and Tardos, Eva}, issn = {0196-6774}, journal = {Journal of Algorithms}, number = {2}, pages = {314--332}, publisher = {Elsevier}, title = {{Scheduling data transfers in a network and the set scheduling problem}}, doi = {10.1016/s0196-6774(03)00054-3}, volume = {48}, year = {2003}, } @inproceedings{11897, abstract = {This paper addresses the problem of topic distillation on the World Wide Web, namely, given a typical user query to find quality documents related to the query topic. Connectivity analysis has been shown to be useful in identifying high quality pages within a topic specific graph of hyperlinked documents. The essence of our approach is to augment a previous connectivity analysis based algorithm with content analysis. We identify three problems with the existing approach and devise algorithms to tackle them. The results of a user evaluation are reported that show an improvement of precision at 10 documents by at least 45% over pure connectivity analysis. }, author = {Bharat, Krishna and Henzinger, Monika H}, booktitle = {21st annual international ACM SIGIR conference on Research and development in information retrieval}, isbn = {978-1-58113-015-7}, issn = {01635840}, location = {Melbourne, Australia}, pages = {104–111}, publisher = {Association for Computing Machinery}, title = {{Improved algorithms for topic distillation in a hyperlinked environment}}, doi = {10.1145/290941.290972}, year = {2003}, } @inproceedings{11860, abstract = {Many daily activities present information in the form of a stream of text, and often people can benefit from additional information on the topic discussed. TV broadcast news can be treated as one such stream of text; in this paper we discuss finding news articles on the web that are relevant to news currently being broadcast.We evaluated a variety of algorithms for this problem, looking at the impact of inverse document frequency, stemming, compounds, history, and query length on the relevance and coverage of news articles returned in real time during a broadcast. We also evaluated several postprocessing techniques for improving the precision, including reranking using additional terms, reranking by document similarity, and filtering on document similarity. For the best algorithm, 84%-91% of the articles found were relevant, with at least 64% of the articles being on the exact topic of the broadcast. In addition, a relevant article was found for at least 70% of the topics.}, author = {Henzinger, Monika H and Chang, Bay-Wei and Milch, Brian and Brin, Sergey}, booktitle = {Proceedings of the 12th international conference on World Wide Web}, isbn = {978-158113680-7}, location = {Budapest, Hungary}, publisher = {Association for Computing Machinery}, title = {{Query-free news search}}, doi = {10.1145/775152.775154}, year = {2003}, } @inproceedings{11909, abstract = {This article presents a high-level discussion of some problems that are unique to web search engines. The goal is to raise awareness and stimulate research in these areas.}, author = {Henzinger, Monika H and Motwani, Rajeev and Silverstein, Craig}, booktitle = {18th International Joint Conference on Artificial Intelligence}, issn = {1045-0823}, location = {Acapulco, Mexico}, pages = {1573--1579}, publisher = {Association for Computing Machinery}, title = {{Challenges in web search engines}}, year = {2003}, } @article{1457, abstract = {Among the major mathematical approaches to mirror symmetry are those of Batyrev-Borisov and Stromdnger-Yau-Zaslow (SYZ). The first is explicit and amenable to computation but is not clearly related to the physical motivation; the second is the opposite. Furthermore, it is far from obvious that mirror partners in one sense will also be mirror partners in the other. This paper concerns a class of examples that can be shown to satisfy the requirements of SYZ, but whose Hodge numbers are also equal. This provides significant evidence in support of SYZ. Moreover, the examples are of great interest in their own right: they are spaces of flat SLr-connections on a smooth curve. The mirror is the corresponding space for the Langlands dual group PGLr. These examples therefore throw a bridge from mirror symmetry to the duality theory of Lie groups and, more broadly, to the geometric Langlands program.}, author = {Tamas Hausel and Thaddeus, Michael}, journal = {Inventiones Mathematicae}, number = {1}, pages = {197 -- 229}, publisher = {Springer}, title = {{Mirror symmetry, langlands duality, and the Hitchin system}}, doi = {10.1007/s00222-003-0286-7}, volume = {153}, year = {2003}, } @article{1458, abstract = {The moduli space of stable bundles of rank $2$ and degree $1$ on a Riemann surface has rational cohomology generated by the so-called universal classes. The work of Baranovsky, King-Newstead, Siebert-Tian and Zagier provided a complete set of relations between these classes, expressed in terms of a recursion in the genus. This paper accomplishes the same thing for the noncompact moduli spaces of Higgs bundles, in the sense of Hitchin and Simpson. There are many more independent relations than for stable bundles, but in a sense the answer is simpler, since the formulas are completely explicit, not recursive. The results of Kirwan on equivariant cohomology for holomorphic circle actions are of key importance.}, author = {Tamas Hausel and Thaddeus, Michael}, journal = {Journal of the American Mathematical Society}, number = {2}, pages = {303 -- 329}, publisher = {American Mathematical Society}, title = {{Relations in the cohomology ring of the moduli space of rank 2 Higgs bundles}}, doi = {10.1090/S0894-0347-02-00417-4}, volume = {16}, year = {2003}, } @article{1459, abstract = {In this paper we explicitly calculate the analogue of the 't Hooft SU (2) Yang-Mills instantons on Gibbons-Hawking multi-centered gravitational instantons, which come in two parallel families: the multi-Eguchi-Hanson, or Ak ALE gravitational instantons and the multi-Taub-NUT spaces, or Ak ALF gravitational instantons. We calculate their energy and find the reducible ones. Following Kronheimer we also exploit the U(1) invariance of our solutions and study the corresponding explicit singular SU (2) magnetic monopole solutions of the Bogomolny equations on flat ℝ3.}, author = {Etesi, Gábor and Tamas Hausel}, journal = {Communications in Mathematical Physics}, number = {2}, pages = {275 -- 288}, publisher = {Springer}, title = {{On Yang-Mills instantons over multi-centered gravitational instantons}}, doi = {10.1007/s00220-003-0806-8}, volume = {235}, year = {2003}, } @article{166, abstract = {For any number field k, upper bounds are established for the number of k-rational points of bounded height on non-singular del Pezzo surfaces defined over k, which are equipped with suitable conic bundle structures over k.}, author = {Browning, Timothy D and Swarbick Jones, M}, journal = {Proceedings of the Bonn session in analytic number theory and diophantine equations}, publisher = {Mathematisches Institut der Universität Bonn}, title = {{Counting rational points on del Pezzo surfaces of degree 5}}, volume = {360}, year = {2003}, } @article{1959, abstract = {The molecular organization of bacterial NADH: ubiquinone oxidoreductase (complex I or NDH-1) is not established, apart from a rough separation into dehydrogenase, connecting and membrane domains. In this work, complex I was purified from Escherichia coli and fragmented by replacing dodecylmaltoside with other detergents. Exchange into decyl maltoside led to the removal of the hydrophobic subunit NuoL from the otherwise intact complex. Diheptanoyl phosphocholine led to the loss of NuoL and NuoM subunits, whereas other subunits remained in the complex. The presence of N,N-dimethyldodecylamine N-oxide or Triton X-100 led to further disruption of the membrane domain into fragments containing NuoL/M/N, NuoA/K/N, and NuoH/J subunits. Among the hydrophilic subunits, NuoCD was most readily dissociated from the complex, whereas NuoB was partially dissociated from the peripheral arm assembly in N,N-dimethyldodecylamine N-oxide. A model of subunit arrangement in bacterial complex I based on these data is proposed. Subunits NuoL and NuoM, which are homologous to antiporters and are implicated in proton pumping, are located at the distal end of the membrane arm, spatially separated from the redox centers of the peripheral arm. This is consistent with proposals that the mechanism of proton pumping by complex I is likely to involve long range conformational changes.}, author = {Holt, Peter J and Morgan, David J and Leonid Sazanov}, journal = {Journal of Biological Chemistry}, number = {44}, pages = {43114 -- 43120}, publisher = {American Society for Biochemistry and Molecular Biology}, title = {{The location of NuoL and NuoM subunits in the membrane domain of the Escherichia coli Complex I: implications for the mechanism of proton pumping}}, doi = {10.1074/jbc.M308247200}, volume = {278}, year = {2003}, } @article{1960, abstract = {NADH-ubiquinone oxidoreductase (complex I or NDH-1) was purified from the BL21 strain of Escherichia coli using an improved procedure. The complex was effectively stabilized by addition of divalent cations and lipids, making the preparation suitable for structural studies. The ubiquinone reductase activity of the enzyme was fully restored by addition of native E. coli lipids. Two different two-dimensional crystal forms, with p2 and p3 symmetry, were obtained using lipids containing native E. coli extracts. Analysis of the crystals showed that they are formed by fully intact complex I in an L-shaped conformation. Activity assays and single particle analysis indicated that complex I maintains this structure in detergent solution and does not adopt a different conformation in the active state. Thus, we provide the first experimental evidence that complex I from E. coli has an L-shape in a lipid bilayer and confirm that this is also the case for the active enzyme in solution. This suggests strongly that bacterial complex I exists in an L-shaped conformation in vivo. Our results also indicate that native lipids play an important role in the activation, stabilization and, as a consequence, crystallization of purified complex I from E. coli.}, author = {Leonid Sazanov and Carroll, Joe D and Holt, Peter J and Toime, Laurence J and Fearnley, Ian M}, journal = {Journal of Biological Chemistry}, number = {21}, pages = {19483 -- 19491}, publisher = {American Society for Biochemistry and Molecular Biology}, title = {{A role for native lipids in the stabilization and two dimensional crystallization of the Escherichia coli NADH ubiquinone oxidoreductase (complex I)}}, doi = {10.1074/jbc.M208959200}, volume = {278}, year = {2003}, } @article{205, author = {Timothy Browning}, journal = {Acta Arithmetica}, number = {3}, pages = {275 -- 295}, publisher = {Instytut Matematyczny}, title = {{Counting rational points on cubic and quartic surfaces}}, doi = {10.4064/aa108-3-7}, volume = {108}, year = {2003}, } @article{206, abstract = {Let T ⊂ ℙ 4 be a non-singular threefold of degree at least four. Then we show that the number of points in T(ℚ), with height at most B, is o(B 3) or B → ∞.}, author = {Timothy Browning}, journal = {Quarterly Journal of Mathematics}, number = {1}, pages = {33 -- 39}, publisher = {Unknown}, title = {{A note on the distribution of rational points on threefolds}}, doi = {10.1093/qjmath/54.1.33}, volume = {54}, year = {2003}, } @article{207, author = {Browning, Timothy D}, journal = {Mathematical Proceedings of the Cambridge Philosophical Society}, number = {3}, pages = {385 -- 395}, publisher = {Cambridge University Press}, title = {{Sums of four biquadrates}}, doi = {10.1017/S0305004102006382}, volume = {134}, year = {2003}, } @article{208, abstract = {For any ε > 0 and any diagonal quadratic form Q ∈ ℤ[x 1, x 2, x 3, x 4] with a square-free discriminant of modulus Δ Q ≠ 0, we establish the uniform estimate ≪ε B 3/2+ε + B 2+ε/Δ Q 1/6 for the number of rational points of height at most B lying in the projective surface Q = 0.}, author = {Timothy Browning}, journal = {Quarterly Journal of Mathematics}, number = {1}, pages = {11 -- 31}, publisher = {Oxford University Press}, title = {{Counting rational points on diagonal quadratic surfaces}}, doi = {10.1093/qjmath/54.1.11}, volume = {54}, year = {2003}, } @inproceedings{2337, author = {Lieb, Élliott H and Robert Seiringer}, editor = {Karpeshina, Yulia and Weikard, Rudi and Zeng, Yanni}, pages = {239 -- 250}, publisher = {American Mathematical Society}, title = {{Bose-Einstein condensation of dilute gases in traps }}, doi = {10.1090/conm/327/05818}, volume = {327}, year = {2003}, } @article{2357, abstract = {The classic Poincaré inequality bounds the L q-norm of a function f in a bounded domain Ω ⊂ ℝ n in terms of some L p-norm of its gradient in Ω. We generalize this in two ways: In the first generalization we remove a set Τ from Ω and concentrate our attention on Λ = Ω \ Τ. This new domain might not even be connected and hence no Poincaré inequality can generally hold for it, or if it does hold it might have a very bad constant. This is so even if the volume of Τ is arbitrarily small. A Poincaré inequality does hold, however, if one makes the additional assumption that f has a finite L p gradient norm on the whole of Ω, not just on Λ. The important point is that the Poincaré inequality thus obtained bounds the L q-norm of f in terms of the L p gradient norm on Λ (not Ω) plus an additional term that goes to zero as the volume of Τ goes to zero. This error term depends on Τ only through its volume. Apart from this additive error term, the constant in the inequality remains that of the 'nice' domain Ω. In the second generalization we are given a vector field A and replace ∇ by ∇ + iA(x) (geometrically, a connection on a U(1) bundle). Unlike the A = 0 case, the infimum of ∥(∇ + iA)f∥ p over all f with a given ∥f∥ q is in general not zero. This permits an improvement of the inequality by the addition of a term whose sharp value we derive. We describe some open problems that arise from these generalizations.}, author = {Lieb, Élliott H and Robert Seiringer and Yngvason, Jakob}, journal = {Annals of Mathematics}, number = {3}, pages = {1067 -- 1080}, publisher = {Princeton University Press}, title = {{Poincaré inequalities in punctured domains}}, doi = {10.4007/annals.2003.158.1067 }, volume = {158}, year = {2003}, } @article{2354, abstract = {We investigate the ground state properties of a gas of interacting particles confined in an external potential in three dimensions and subject to rotation around an axis of symmetry. We consider the Gross-Pitaevskii (GP) limit of a dilute gas. Analysing both the absolute and the bosonic ground states of the system, we show, in particular, their different behaviour for a certain range of parameters. This parameter range is determined by the question whether the rotational symmetry in the minimizer of the GP functional is broken or not. For the absolute ground state, we prove that in the GP limit a modified GP functional depending on density matrices correctly describes the energy and reduced density matrices, independent of symmetry breaking. For the bosonic ground state this holds true if and only if the symmetry is unbroken.}, author = {Robert Seiringer}, journal = {Journal of Physics A: Mathematical and Theoretical}, number = {37}, pages = {9755 -- 9778}, publisher = {IOP Publishing Ltd.}, title = {{Ground state asymptotics of a dilute, rotating gas}}, doi = {10.1088/0305-4470/36/37/312}, volume = {36}, year = {2003}, } @article{2358, abstract = {A study was conducted on the one-dimensional (1D) bosons in three-dimensional (3D) traps. A rigorous analysis was carried out on the parameter regions in which various types of 1D or 3D behavior occurred in the ground state. The four parameter regions include density, transverse, longitudinal dimensions and scattering length.}, author = {Lieb, Élliott H and Robert Seiringer and Yngvason, Jakob}, journal = {Physical Review Letters}, number = {15}, pages = {1504011 -- 1504014}, publisher = {American Physical Society}, title = {{One-dimensional Bosons in three-dimensional traps}}, doi = {10.1103/PhysRevLett.91.150401}, volume = {91}, year = {2003}, } @phdthesis{2414, author = {Uli Wagner}, publisher = {ETH Zurich}, title = {{On k-Sets and Their Applications}}, doi = {10.3929/ethz-a-004708408}, year = {2003}, } @inproceedings{2424, abstract = {We introduce the adaptive neighborhood graph as a data structure for modeling a smooth manifold M embedded in some (potentially very high-dimensional) Euclidean space ℝd. We assume that M is known to us only through a finite sample P ⊂ M, as it is often the case in applications. The adaptive neighborhood graph is a geometric graph on P. Its complexity is at most min{2O(k)(n, n2}, where n = |P| and k = dim M, as opposed to the n⌈d/2⌉ complexity of the Delaunay triangulation, which is often used to model manifolds. We show that we can provably correctly infer the connectivity of M and the dimension of M from the adaptive neighborhood graph provided a certain standard sampling condition is fulfilled. The running time of the dimension detection algorithm is d2O(k7 log k) for each connected component of M. If the dimension is considered constant, this is a constant-time operation, and the adaptive neighborhood graph is of linear size. Moreover, the exponential dependence of the constants is only on the intrinsic dimension k, not on the ambient dimension d. This is of particular interest if the co-dimension is high, i.e., if k is much smaller than d, as is the case in many applications. The adaptive neighborhood graph also allows us to approximate the geodesic distances between the points in P.}, author = {Giesen, Joachim and Uli Wagner}, pages = {329 -- 337}, publisher = {ACM}, title = {{Shape dimension and intrinsic metric from samples of manifolds with high co-dimension}}, doi = {10.1145/777792.777841}, year = {2003}, } @inproceedings{2423, abstract = {A finite set N ⊃ Rd is a weak ε-net for an n-point set X ⊃ Rd (with respect to convex sets) if N intersects every convex set K with |K ∩ X| ≥ εn. We give an alternative, and arguably simpler, proof of the fact, first shown by Chazelle et al. [7], that every point set X in Rd admits a weak ε-net of cardinality O(ε-d polylog(1/ε)). Moreover, for a number of special point sets (e.g., for points on the moment curve), our method gives substantially better bounds. The construction yields an algorithm to construct such weak ε-nets in time O(n ln(1/ε)). We also prove, by a different method, a near-linear upper bound for points uniformly distributed on the (d - 1)-dimensional sphere.}, author = {Matoušek, Jiří and Uli Wagner}, pages = {129 -- 135}, publisher = {ACM}, title = {{New constructions of weak epsilon-nets}}, doi = {10.1145/777792.777813}, year = {2003}, } @inproceedings{2422, abstract = {We prove a lower bound of 0.3288(4 n) for the rectilinear crossing number cr̄(Kn) of a complete graph on n vertices, or in other words, for the minimum number of convex quadrilaterals in any set of n points in general position in the Euclidean plane. As we see it, the main contribution of this paper is not so much the concrete numerical improvement over earlier bounds, as the novel method of proof, which is not based on bounding cr̄(Kn) for some small n.}, author = {Uli Wagner}, pages = {583 -- 588}, publisher = {SIAM}, title = {{On the rectilinear crossing number of complete graphs}}, year = {2003}, } @article{2623, abstract = {Patients with Hodgkin's disease can develop paraneoplastic cerebellar ataxia because of the generation of autoantibodies against mGluR1 (mGluR1-Abs). Yet, the pathophysiological mechanisms underlying their motor coordination deficits remain to be elucidated. Here, we show that application of IgG purified from the patients' serum to cerebellar slices of mice acutely reduces the basal activity of Purkinje cells, whereas application to the flocculus of mice in vivo evokes acute disturbances in the performance of their compensatory eye movements. In addition, the mGluR1-Abs block induction of long-term depression in cultured mouse Purkinje cells, whereas the cerebellar motor learning behavior of the patients is affected in that they show impaired adaptation of their saccadic eye movements. Finally, postmortem analysis of the cerebellum of a paraneoplastic cerebellar ataxia patient showed that the number of Purkinje cells was significantly reduced by approximately two thirds compared with three controls. We conclude that autoantibodies against mGluR1 can cause cerebellar motor coordination deficits caused by a combination of rapid effects on both acute and plastic responses of Purkinje cells and chronic degenerative effects.}, author = {Coesmans, Michiel P and Sillevis-Smitt, Peter A and Linden, David J and Ryuichi Shigemoto and Hirano, Tomoo and Yamakawa, Yoshinori and Van Alphen, Adriaan M and Luo, Chongde and Van Der Geest, Jos N and Kros, Johan M and Gaillard, Carlo A and Frens, Maarten A and De Zeeuw, Chris I}, journal = {Annals of Neurology}, number = {3}, pages = {325 -- 336}, publisher = {Wiley-Blackwell}, title = {{Mechanisms underlying cerebellar motor deficits due to mGluR1-autoantibodies}}, doi = {10.1002/ana.10451}, volume = {53}, year = {2003}, } @article{2625, abstract = {Metabotropic glutamate receptor 1 (mGluR1) plays a crucial role in synaptic plasticity and motor learning in the cerebellum. We have studied activity-dependent changes in mGluR1 function in mouse cultured Purkinje neurons. Depolarizing stimulation potentiated Ca2+ and current responses to an mGluR1 agonist for several hours in the cultured Purkinje neurons. It also blocked internalization of mGluR1 and increased the number of mGluR1s on the cell membrane. We found that depolarization simultaneously increased transcription of Homer1a in Purkinje neurons. Homer1a inhibited internalization and increased cell-surface expression of mGluR1 when coexpressed in human embryonic kidney (HEK)-293 cells. Depolarization-induced Homer1a expression in Purkinje neurons was blocked by a mitogen-activated protein kinase (MAPK) inhibitor. Changes in internalization and mGluR1-mediated Ca2+ response were also blocked by inhibition of MAPK activity, suggesting that localization and activity of mGluR1 were regulated in the same signalling pathway as Homer1a expression. It is thus suggested that depolarization of the Purkinje neuron leads to the increment in mGluR1 responsiveness through MAPK activity and induction of Homer1a expression, which increases active mGluR1 on the cell surface by blocking internalization of mGluR1.}, author = {Minami, Itsunari and Kengaku, Mineko and Smitt, Sillevis P and Ryuichi Shigemoto and Hirano, Tomoo}, journal = {European Journal of Neuroscience}, number = {5}, pages = {1023 -- 1032}, publisher = {Wiley-Blackwell}, title = {{Long-term potentiation of mGluR1 activity by depolarization-induced Homer1a in mouse cerebellar Purkinje neurons}}, doi = {10.1046/j.1460-9568.2003.02499.x}, volume = {17}, year = {2003}, } @article{2626, abstract = {The expression pattern of metabotropic glutamate receptor Iα (mGluR1α) was immunohistochemically investigated in substantia nigra dopaminergic neurons of the macaque monkey. In normal monkeys, mGluR1α immunoreactivity was weakly observed in the dorsal tier of the substantia nigra pars compacta (SNc-d) where calbindin-D28k-containing dopaminergic neurons invulnerable to parkinsonian degeneration are specifically located. On the other hand, mGluR1α was strongly expressed in the ventral tier of the substantia nigra pars cornpacta (SNc-v). In monkeys treated with the parkinsonism-inducing drug, I-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), mGluR1α expression was decreased in dopaminergic neurons in the SNc-v that were spared its toxic action. These results suggest that mGluR1α expression may be involved at least partly in the vulnerability of dopaminergic neurons to parkinsonian insults.}, author = {Kaneda, Katsuyuki and Imanishi, Michiko and Nambu, Atsushi and Ryuichi Shigemoto and Takada, Masahiko}, journal = {Neuroreport}, number = {7}, pages = {947 -- 950}, publisher = {Lippincott, Williams & Wilkins}, title = {{Differential expression patterns of mGluR1α in monkey nigral dopamine neurons}}, doi = {10.1097/01.wnr.0000074344.81633.e4}, volume = {14}, year = {2003}, } @article{2627, abstract = {Despite its implications for higher order functions of the brain, little is currently known about the molecular basis of left-right asymmetry of the brain. Here we report that synaptic distribution of N-methyl-D-aspartate (NMDA) receptor GluRε2 (NR2B) subunits in the adult mouse hippocampus is asymmetrical between the left and right and between the apical and basal dendrites of single neurons. These asymmetrical allocations of ε2 subunits differentiate the properties of NMDA receptors and synaptic plasticity between the left and right hippocampus. These results provide a molecular basis for the structural and functional asymmetry of the mature brain.}, author = {Kawakami, Ryosuke and Shinohara, Yoshiaki and Kato, Yuichiro and Sugiyama, Hiroyuki and Ryuichi Shigemoto and Ito, Isao}, journal = {Science}, number = {5621}, pages = {990 -- 994}, publisher = {American Association for the Advancement of Science}, title = {{Asymmetrical allocation of NMDA receptor ε2 subunits in hippocampal circuitry}}, doi = {10.1126/science.1082609}, volume = {300}, year = {2003}, } @article{2629, abstract = {The release of neurotransmitters is modulated by presynaptic metabotropic glutamate receptors (mGluRs), which show a highly selective expression and subcellular location in glutamatergic terminals in the hippocampus. Using immunocytochemistry, we investigated whether one of the receptors, mGluR7, whose level of expression is governed by the postsynaptic target, was present in GABAergic terminals and whether such terminals targeted particular cells. A total of 165 interneuron dendritic profiles receiving 466 synapses (82% mGluR7a-positive) were analysed. The presynaptic active zones of most GAD-(77%) or GABA-positive (94%) synaptic boutons on interneurons innervated by mGluR7a-enriched glutamatergic terminals (mGluR7a-decorated) were immunopositive for mGluR7a. GABAergic terminals on pyramidal cells and most other interneurons in str. oriens were mGluR7a-immunonegative. The mGluR7a-decorated cells were mostly somatostatin- and mGluR1α-immunopositive neurons in str. oriens and the alveus. Their GABAergic input mainly originated from VIP-positive terminals, 90% of which expressed high levels of mGluR7a in the presynaptic active zone. Parvalbumin-positive synaptic terminals were rare on mGluR7a-decorated cells, but on these neurons 73% of them were mGluR7a-immunopositive. Some type II synapses innervating interneurons were immunopositive for mGluR7b, as were some type I synapses. Because not all target cells of VIP-positive neurons are known it has not been possible to determine whether mGluR7 is expressed in a target-cell-specific manner in the terminals of single GABAergic cells. The activation of mGluR7 may decrease GABA release to mGluR7-decorated cells at times of high pyramidal cell activity, which elevates extracellular glutamate levels. Alternatively, the presynaptic receptor may be activated by as yet unidentified endogenous ligands released by the GABAergic terminals or the postsynaptic dendrites.}, author = {Somogyi, Péter and Dalezios, Yannis and Luján, Rafael and Roberts, John D and Watanabe, Masahiko and Ryuichi Shigemoto}, journal = {European Journal of Neuroscience}, number = {12}, pages = {2503 -- 2520}, publisher = {Wiley-Blackwell}, title = {{High level of mGluR7 in the presynaptic active zones of select populations of GABAergic terminals innervating interneurons in the rat hippocampus}}, doi = {10.1046/j.1460-9568.2003.02697.x}, volume = {17}, year = {2003}, } @article{2628, abstract = {We aimed to estimate the number of AMPA receptors (AMPARs) bound by the quantal transmitter packet, their single-channel conductance and their density in the postsynaptic membrane at cerebellar Purkinje cell synapses. The synaptic and extrasynaptic AMPARs were examined in Purkinje cells in 2- to 4-day-old rats, when they receive synaptic inputs solely from climbing fibres (CFs). Evoked CF EPSCs and whole-cell AMPA currents displayed roughly linear current-voltage relationships, consistent with the presence of GluR2 subunits in synaptic and extrasynaptic AMPARs. The mean quantal size, estimated from the miniature EPSCs (MEPSCs), was ∼300 pS. Peak-scaled non-stationary fluctuation analysis of spontaneous EPSCs and MEPSCs gave a weighted-mean synaptic channel conductance of ∼5 pS (∼7 pS when corrected for filtering). By applying non-stationary fluctuation analysis to extrasynaptic currents activated by brief glutamate pulses (5 mM), we also obtained a small single-channel conductance estimate for extrasynaptic AMPARs (∼11 pS). This approach allowed us to obtain a maximum open probability (Po,max) value for the extrasynaptic receptors (Po,max = 0.72). Directly resolved extrasynaptic channel openings in the continued presence of glutamate exhibited clear multiple-conductance levels. The mean area of the postsynaptic density (PSD) of these synapses was 0.074 μm2, measured by reconstructing electron-microscopic (EM) serial sections. Postembedding immunogold labelling by anti-GluR2/3 antibody revealed that AMPARs are localised in PSDs. From these data and by simulating error factors, we estimate that at least 66 AMPARs are bound by a quantal transmitter packet at CF-Purkinje cell synapses, and the receptors are packed at a minimum density of ∼900 μm-2 in the postsynaptic membrane.}, author = {Momiyama, Akiko and Silver, Rachel A and Häusser, Michael A and Notomi, Takuya and Wu, Yue and Ryuichi Shigemoto and Cull-Candy, Stuart G}, journal = {Journal of Physiology}, number = {1}, pages = {75 -- 92}, publisher = {Wiley-Blackwell}, title = {{The density of AMPA receptors activated by a transmitter quantum at the climbing fibre - Purkinje cell synapse in immature rats}}, doi = {10.1113/jphysiol.2002.033472}, volume = {549}, year = {2003}, } @article{2631, abstract = {Cyclic ADP-ribose (cADP-ribose) is a putative second messenger or modulator. However, the role of cADP-ribose in the downstream signals of the metabotropic glutamate receptors (mGluRs) is unclear. Here, we show that glutamate stimulates ADP-ribosyl cyclase activity in rat or mouse crude membranes of retina via group III mGluRs or in superior cervical ganglion via group I mGluRs. The retina of mGluR6-deficient mice showed no increase in the ADP-ribosyl cyclase level in response to glutamate. GTP enhanced the initial rate of basal and glutamate-stimulated cyclase activity. GTP-γ-S also stimulated basal activity. To determine whether the coupling mode of mGluRs to ADP-ribosyl cyclase is a feature common to individual cloned mGluRs, we expressed each mGluR subtype in NG108-15 neuroblastoma x glioma hybrid cells. The glutamate-induced stimulation of the cyclase occurs preferentially in NG108-15 cells over-expressing mGluRs1, 3, 5, and 6. Cells expressing mGluR2 or mGluRs4 and 7 exhibit inhibition or no coupling, respectively. Glutamate-induced activation or inhibition of the cyclase activity was eliminated after pre-treatment with cholera or pertussis toxin, respectively. Thus, the subtype-specific coupling of mGluRs to ADP-ribosyl cyclase via G proteins suggests that some glutamate-evoked neuronal functions are mediated by cADP-ribose.}, author = {Higashida, Haruhiro and Zhang, Jia-Sheng and Mochida, Sumiko and Chen, Xiao-Liang and Shin, Yeonsook and Noda, Mami and Hossain, Kazi Z and Hoshi, Naoto and Hashii, Minako and Ryuichi Shigemoto and Nakanishi, Shigetada and Fukuda, Yutaka and Yokoyama, Shigeru}, journal = {Journal of Neurochemistry}, number = {5}, pages = {1148 -- 1158}, publisher = {Wiley-Blackwell}, title = {{Subtype-specific coupling with ADP-ribosyl cyclase of metabotropic glutamate receptors in retina, cervical superior ganglion and NG108-15 cells}}, doi = {10.1046/j.1471-4159.2003.01751.x}, volume = {85}, year = {2003}, } @article{2633, abstract = {The modulation of calcium channels by metabotropic glutamate receptors (mGluRs) is a key event in the fine-tuning of neurotransmitter release. Here we report that, in cerebrocortical nerve terminals of adult rats, the inhibition of glutamate release is mediated by mGluR7. In this preparation, the major component of glutamate release is supported by P/Q-type Ca2+ channels (72.7%). However, mGluR7 selectively reduced the release component that is associated with N-type Ca2+ channels (29.9%). Inhibition of P/Q channels by mGluR7 is not masked by the higher efficiency of these channels in driving glutamate release when compared with N-type channels. Thus, activation of mGluR7 failed to reduce the release associated with P/Q channels when the extracellular calcium concentration, ([Ca2+]o), was reduced from 1.3 to 0.5 mM. Through Ca2+ imaging, we show that Ca2+ channels are distributed in a heterogeneous manner in individual nerve terminals. Indeed, in this preparation, nerve terminals were observed that contain N-type (31.1%; conotoxin GVIA-sensitive) or P/Q-type (64.3%; agatoxin IVA-sensitive) channels or that were insensitive to these two toxins (4.6%). Interestingly, the great majority of the responses to L-AP4 (95.4%) were observed in nerve terminals containing N-type channels. This specific co-localization of mGluR7 and N-type Ca2+-channels could explain the failure of the receptor to inhibit the P/Q channel-associated release component and also reveal the existence of specific targeting mechanisms to localize the two proteins in the same nerve terminal subset.}, author = {Millán, Carmelo and Castro, Enrique G and Torres, Magdalena and Ryuichi Shigemoto and Sánchez-Prieto, José}, journal = {Journal of Biological Chemistry}, number = {26}, pages = {23955 -- 23962}, publisher = {American Society for Biochemistry and Molecular Biology}, title = {{Co-expression of metabotropic glutamate receptor 7 and N-type Ca2+ channels in single cerebrocortical nerve terminals of adult rats}}, doi = {10.1074/jbc.M211471200}, volume = {278}, year = {2003}, } @article{2632, abstract = {In many brain regions, hyperpolarization-activated cationic currents (Ih) are involved in the generation of rhythmic activities, but the role of Ih in olfactory oscillations remains unclear. Knowledge of the cellular and subcellular distributions of hyperpolarization-activated and cyclic nucleotide-gated channel (HCN) subunits is necessary for understanding the role of Ih in olfactory network activities. Using light microscopic immunocytochemistry, we demonstrate strong HCN1 labelling of the glomerular layer and moderate staining of granule cell, internal and external plexiform layers of the rat main olfactory bulb. In the glomerular layer, among many unlabelled neurons, two distinct subpopulations of juxtaglomerular cells are labelled. Approximately 10% of the juxtaglomerular cells strongly express HCN1. These small diameter cells are immunoreactive for GABA and comprise a subpopulation of periglomerular cells. An additional subset of juxtaglomerular cells (≈ 1%) expresses low levels of HCN1. They are large in diameter, GABA immunonegative but immunopositive for vesicular glutamate transporter 2, characterizing them as external tufted cells. Quantitative immunogold localization revealed that the somatic plasma membranes of periglomerular cells contain approximately four times more HCN1 labelling than those of external tufted cells. Unlike in cortical pyramidal cells, immunogold density for HCN1 does not significantly differ in somatic and dendritic plasma membranes of external tufted cells, indicating that post-synaptic potentials arriving at proximal and distal dendrites are modulated by the same density of I h. Our results demonstrate a cell type-dependent expression of HCN1 in the olfactory bulb and predict a differential contribution of distinct juxtaglomerular cell types to network oscillations.}, author = {Holderith, Noémi B and Ryuichi Shigemoto and Nusser, Zoltán}, journal = {European Journal of Neuroscience}, number = {2}, pages = {344 -- 354}, publisher = {Wiley-Blackwell}, title = {{Cell type-dependent expression of HCN1 in the main olfactory bulb}}, doi = {10.1046/j.1460-9568.2003.02756.x}, volume = {18}, year = {2003}, } @article{2635, abstract = {Metabotropic GABAB receptors mediate slow inhibitory effects presynaptically and postsynaptically. Using preembedding immunohistochemical methods combined with quantitative analysis of GABAB receptor subunit immunoreactivity, this study provides a detailed description of the cellular and subcellular localization of GABAB1a/b and GABA B2 in the rat hippocampus. At the light microscopic level, an overlapping distribution of GABAB1a/b and GABAB2 was revealed in the dendritic layers of the hippocampus. In addition, expression of the GABAB1a/b subunit was found in somata of CA1 pyramidal cells and of a subset of GABAergic interneurons. At the electron microscopic level, immunoreactivity for both subunits was observed on presynaptic and, more abundantly, on postsynaptic elements. Presynaptically, subunits were mainly detected in the extrasynaptic membrane and occasionally over the presynaptic membrane specialization of putative glutamatergic and, to a lesser extent, GABAergic axon terminals. Postsynaptically, the majority of GABAB receptor subunits were localized to the extrasynaptic plasma membrane of spines and dendritic shafts of principal cells and shafts of interneuron dendrites. Quantitative analysis revealed enrichment of GABAB1a/b around putative glutamatergic synapses on spines and an even distribution on dendritic shafts of pyramidal cells contacted by GABAergic boutons. The association of GABAB receptors with glutamatergic synapses at both presynaptic and postsynaptic sides indicates their intimate involvement in the modulation of glutamatergic neurotransmission. The dominant extrasynaptic localization of GABAB receptor subunits suggests that their activation is dependent on spillover of GABA requiring simultaneous activity of populations of GABAergic cells as it occurs during population oscillations or epileptic seizures.}, author = {Kulik, Ákos and Vida, Imre and Luján, Rafael and Haas, Carola A and López-Bendito, Guillermina and Ryuichi Shigemoto and Frotscher, Michael}, journal = {Journal of Neuroscience}, number = {35}, pages = {11026 -- 11035}, publisher = {Society for Neuroscience}, title = {{Subcellular Localization of Metabotropic GABAB Receptor Subunits GABAB1a/b and GABAB2 in the Rat Hippocampus}}, volume = {23}, year = {2003}, } @article{2634, abstract = {To better understand the role of neurotransmitter receptors in neuronal differentiation and maturation a detailed knowledge of their identity, location and function in the plasma membrane of specific neuronal populations during development is required. Combining pre-embedding immunocytochemistry with cell tracking in embryonic brain slice cultures we show that virtually all neurons (∼98%) migrating through the lower intermediate zone (LIZ) on their way from the medial ganglionic eminence to the cerebral cortex, express GABA BR1. Blockade of GABABRs with a specific antagonist, CGP52432, resulted in a concentration-dependent accumulation of these tangentially migrating neurons in the ventricular/subventricular zones (VZ/SVZ) of the cortex and fewer cells were observed in the cortical plate/marginal zone (CP/MZ) and LIZ. Moreover, they had significantly shorter leading processes compared with similar migrating cells in control slices. Electrophysiological recording in LIZ and CP cells revealed no direct effect of either CGP52432 or the GABABR agonist, baclofen, on resting membrane properties suggesting that the effect of CGP52432 on migration might be mediated through a metabotropic action or the regulation of release of factors controlling migration. These results suggest that GABABRs have an important modulatory role in the migration of cortical interneurons.}, author = {López-Bendito, Guillermina and Luján, Rafael and Ryuichi Shigemoto and Ganter, Paul and Paulsen, Ole and Molnár, Zoltán}, journal = {Cerebral Cortex}, number = {9}, pages = {932 -- 942}, publisher = {Oxford University Press}, title = {{Blockade of GABAB receptors alters the tangential migration of cortical neurons}}, doi = {10.1093/cercor/13.9.932}, volume = {13}, year = {2003}, } @article{2630, abstract = {Taste-metabotropic glutamate receptor 4 (taste-mGluR4) and the heteromers of T1R1 and T1R3 are candidate receptors involved in the sense of umami (monosodium glutamate) taste. Although the expression of group III mGluRs (taste-mGluR4) has been demonstrated in taste tissues, no mention has been made of the expression of group I mGluRs (mGluR1 and mGluR5) in taste tissues. We examined the expression of mGluR1 and mGluR5 in rat gustatory tissues by using reverse transcription-polymerase chain reaction (RT-PCR), in situ hybridization, immunohistochemistry and immunoelectron microscopy. RT-PCR assay showed that mGluR1α and mGluR1β mRNAs were expressed in circumvallate papillae, but mGluR5 mRNA was not expressed. The positive signals of mGluR1 mRNA were detected only in circumvallate taste buds by in situ hybridization analysis. In cryosections of fungiform, foliate and circumvallate papillae, the antibody against mGluRla gave intense labeling on the taste hairs in all taste pores examined. In the developing taste buds, the positive signals of mGluR1α in taste hairs gradually increased with the increase in number of taste bud cells. These results show that, in addition to taste-mGluR4 and the heteromer of T1R1 and T1R3, mGluR1α may function as a receptor for glutamate (umami) taste sensation.}, author = {Toyono, Takashi and Seta, Yuji and Kataoka, Shinji and Kawano, Shintaro and Ryuichi Shigemoto and Toyoshima, Kuniaki}, journal = {Cell and Tissue Research}, number = {1}, pages = {29 -- 35}, publisher = {Springer}, title = {{Expression of metabotropic glutamate receptor group I in rat gustatory papillae}}, doi = {10.1007/s00441-003-0740-2}, volume = {313}, year = {2003}, } @article{2637, abstract = {While the cholinergic depletion in Alzheimer's disease (AD) has been known for some time, a definitive involvement of other neurotransmitter systems has been somewhat more elusive. Our study demonstrates a clear involvement of both glutamatergic and, to a lesser extent, GABAergic neurons in an early onset transgenic mouse model of AD-like amyloid pathology. Immunohistochemical staining and subsequent quantification has revealed a statistically significant increased density of glutamatergic and GABAergic presynaptic boutons in both the plaque free and plaque adjacent cortical neuropile areas of transgenic mice as compared to non-transgenic controls. Furthermore, amyloid plaque size was shown to have a statistically significant effect on the relative area occupied by dystrophic glutamatergic neurites in the peri-plaque neuropile. These findings support our hypothesis that the amyloid pathology progresses in a time and neurotransmitter specific manner, first in the cholinergic system which appears to be most vulnerable, followed by the glutamatergic presynaptic boutons and finally the somewhat more resilient GABAergic terminals.}, author = {Bell, Karen F and De Kort, G J and Steggerda, S and Ryuichi Shigemoto and Ribeiro-da-Silva, Alfredo and Cuello, Augusto C}, journal = {Neuroscience Letters}, number = {2}, pages = {143 -- 147}, publisher = {Elsevier}, title = {{Structural involvement of the glutamatergic presynaptic boutons in a transgenic mouse model expressing early onset amyloid pathology}}, doi = {10.1016/j.neulet.2003.09.027}, volume = {353}, year = {2003}, } @article{2784, abstract = {We report the results of an experimental study of magnetohydrodynamic damping of sidewall convection in a rectangular enclosure filled with gallium. In particular we investigate the suppression of convection when a steady magnetic field is applied separately in each of the three principal directions of the flow. The strongest damping of the steady flow is found for a vertical magnetic field, which is in agreement with theory. However, we observe that the application of a field transverse to the flow provides greater damping than a longitudinal one, which seems to contradict available theory. We provide a possible resolution of this apparent dichotomy in terms of the length scale of the experiment.}, author = {Björn Hof and Juel, Anne and Mullin, Tom P}, journal = {Journal of Fluid Mechanics}, pages = {163 -- 179}, publisher = {Cambridge University Press}, title = {{Magnetohydrodynamic damping of convective flows in molten gallium}}, doi = {10.1017/S0022112003004014}, volume = {482}, year = {2003}, } @article{2785, abstract = {Experimental evidence for the scaling of the finite amplitude of perturbation theory required to promote transition in Poiseuille flow was found. The exponent is -1 and was uncovered using considerable care in the design and execution of the experiment. Interestingly, this exponent was also found in experiments on transition in boundary layers.}, author = {Björn Hof and Juel, Anne and Mullin, Tom P}, journal = {Physical Review Letters}, number = {24}, pages = {244502/1 -- 244502/4}, publisher = {American Physical Society}, title = {{Scaling of the turbulence transition threshold in a pipe}}, doi = {10.1103/PhysRevLett.91.244502}, volume = {91}, year = {2003}, } @article{2990, abstract = {Plant growth is marked by its adaptability to continuous changes in environment. A regulated, differential distribution of auxin underlies many adaptation processes including organogenesis, meristem patterning and tropisms. In executing its multiple roles, auxin displays some characteristics of both a hormone and a morphogen. Studies on auxin transport, as well as tracing the intracellular movement of its molecular components, have suggested a possible scenario to explain how growth plasticity is conferred at the cellular and molecular level. The plant perceives stimuli and changes the subcellular position of auxin-transport components accordingly. These changes modulate auxin fluxes, and the newly established auxin distribution triggers the corresponding developmental response.}, author = {Friml, Jirí}, journal = {Current Opinion in Plant Biology}, number = {1}, pages = {7 -- 12}, publisher = {Elsevier}, title = {{Auxin transport - Shaping the plant}}, doi = {10.1016/S1369526602000031}, volume = {6}, year = {2003}, } @article{2992, abstract = {Plants have many polarized cell types, but relatively little is known about the mechanisms that establish polarity. The orc mutant was identified originally by defects in root patterning, and positional cloning revealed that the affected gene encodes STEROL METHYLTRANSFERASE1, which is required for the appropriate synthesis and composition of major membrane sterols. smt1orc mutants displayed several conspicuous cell polarity defects. Columella root cap cells revealed perturbed polar positioning of different organelles, and in the smt1orc root epidermis, polar initiation of root hairs was more randomized. Polar auxin transport and expression of the auxin reporter DR5-β-glucuronidase were aberrant in smt1orc. Patterning defects in smt1orc resembled those observed in mutants of the PIN gene family of putative auxin efflux transporters. Consistently, the membrane localization of the PIN1 and PIN3 proteins was disturbed in smt1orc, whereas polar positioning of the influx carrier AUX1 appeared normal. Our results suggest that balanced sterol composition is a major requirement for cell polarity and auxin efflux in Arabidopsis.}, author = {Willemsen, Viola and Jirí Friml and Grebe, Markus and Van Den Toorn, Albert and Palme, Klaus and Scheres, Ben}, journal = {Plant Cell}, number = {3}, pages = {612 -- 625}, publisher = {American Society of Plant Biologists}, title = {{Cell polarity and PIN protein positioning in Arabidopsis require STEROL METHYLTRANSFERASE1 function}}, doi = {10.1105/tpc.008433}, volume = {15}, year = {2003}, } @article{2996, abstract = {Plants, compared to animals, exhibit an amazing adaptability and plasticity in their development. This is largely dependent on the ability of plants to form new organs, such as lateral roots, leaves, and flowers during postembryonic development. Organ primordia develop from founder cell populations into organs by coordinated cell division and differentiation. Here, we show that organ formation in Arabidopsis involves dynamic gradients of the signaling molecule auxin with maxima at the primordia tips. These gradients are mediated by cellular efflux requiring asymmetrically localized PIN proteins, which represent a functionally redundant network for auxin distribution in both aerial and underground organs. PIN1 polar localization undergoes a dynamic rearrangement, which correlates with establishment of auxin gradients and primordium development. Our results suggest that PIN-dependent, local auxin gradients represent a common module for formation of all plant organs, regardless of their mature morphology or developmental origin. }, author = {Eva Benková and Michniewicz, Marta and Sauer, Michael and Teichmann, Thomas and Seifertová, Daniela and Jürgens, Gerd and Jirí Friml}, journal = {Cell}, number = {5}, pages = {591 -- 602}, publisher = {Cell Press}, title = {{Local, efflux-dependent auxin gradients as a common module for plant organ formation}}, doi = {10.1016/S0092-8674(03)00924-3}, volume = {115}, year = {2003}, } @article{2995, abstract = {Axis formation occurs in plants, as in animals, during early embryogenesis. However, the underlying mechanism is not known. Here we show that the first manifestation of the apical-basal axis in plants, the asymmetric division of the zygote, produces a basal cell that transports and an apical cell that responds to the signalling molecule auxin. This apical-basal auxin activity gradient triggers the specification of apical embryo structures and is actively maintained by a novel component of auxin efflux, PIN7, which is located apically in the basal cell. Later, the developmentally regulated reversal of PIN7 and onset of PIN1 polar localization reorganize the auxin gradient for specification of the basal root pole. An analysis of pin quadruple mutants identifies PIN-dependent transport as an essential part of the mechanism for embryo axis formation. Our results indicate how the establishment of cell polarity, polar auxin efflux and local auxin response result in apical-basal axis formation of the embryo, and thus determine the axiality of the adult plant. }, author = {Jirí Friml and Vieten, Anne and Sauer, Michael and Weijers, Dolf and Schwarz, Heinz and Hamann, Thorsten and Offringa, Remko and Jürgens, Gerd}, journal = {Nature}, number = {6963}, pages = {147 -- 153}, publisher = {Nature Publishing Group}, title = {{Efflux dependent auxin gradients establish the apical basal axis of Arabidopsis}}, doi = {10.1038/nature02085}, volume = {426}, year = {2003}, } @article{2994, abstract = {The regular arrangement of leaves around a plant's stem, called phyllotaxis, has for centuries attracted the attention of philosophers, mathematicians and natural scientists; however, to date, studies of phyllotaxis have been largely theoretical. Leaves and flowers are formed from the shoot apical meristem, triggered by the plant hormone auxin. Auxin is transported through plant tissues by specific cellular influx and efflux carrier proteins. Here we show that proteins involved in auxin transport regulate phyllotaxis. Our data indicate that auxin is transported upwards into the meristem through the epidermis and the outermost meristem cell layer. Existing leaf primordia act as sinks, redistributing auxin and creating its heterogeneous distribution in the meristem. Auxin accumulation occurs only at certain minimal distances from existing primordia, defining the position of future primordia. This model for phyllotaxis accounts for its reiterative nature, as well as its regularity and stability.}, author = {Reinhardt, Didier and Pesce, Eva-Rachele and Stieger, Pia and Mandel, Therese and Baltensperger, Kurt and Bennett, Malcolm and Traas, Jan and Jirí Friml and Kuhlemeier, Cris}, journal = {Nature}, number = {6964}, pages = {255 -- 260}, publisher = {Nature Publishing Group}, title = {{Regulation of phyllotaxis by polar auxin transport}}, doi = {10.1038/nature02081}, volume = {426}, year = {2003}, } @article{2993, abstract = {Plant biology is currently experiencing a growing demand for easy and reliable mRNA and protein localisation techniques. Here, we present novel whole mount in situ hybridisation and immunolocalisation protocols, suitable to localise mRNAs and proteins in Arabidopsis seedlings. We demonstrate that these methods can be used in different organs of Arabidopsis seedlings as well as in other plant species. In order to achieve better reproducibility and higher throughput, we modified these protocols for automation to be performed by a liquid handling robot. In addition, we show that other procedures such as reporter enzyme assays and tissue clearing can be similarly automated. We present examples of application of our protocols including mRNA localisation and proteins and epitope tag (co)localisations which demonstrate that these methods provide reliable and versatile tools for expression, localisation and anatomical studies in plants.}, author = {Jirí Friml and Eva Benková and Mayer, Ulrike and Palme, Klaus and Muster, Gerhard}, journal = {Plant Journal}, number = {1}, pages = {115 -- 124}, publisher = {Wiley-Blackwell}, title = {{Automated whole mount localisation techniques for plant seedlings}}, doi = {10.1046/j.1365-313X.2003.01705.x}, volume = {34}, year = {2003}, } @article{3151, abstract = {Biosynthesis of most peptide hormones and neuropeptides requires proteolytic excision of the active peptide from inactive proprotein precursors, an activity carried out by subtilisin-like proprotein convertases (SPCs) in constitutive or regulated secretory pathways. The Drosophila amontillado (amon) gene encodes a homolog of the mammalian PC2 protein, an SPC that functions in the regulated secretory pathway in neuroendocrine tissues. We have identified amon mutants by isolating ethylmethanesulfonate (EMS)-induced lethal and visible mutations that define two complementation groups in the amon interval at 97D1 of the third chromosome. DNA sequencing identified the amon complementation group and the DNA sequence change for each of the nine amon alleles isolated. amon mutants display partial embryonic lethality, are defective in larval growth, and arrest during the first to second instar larval molt. Mutant larvae can be rescued by heat-shock-induced expression of the amon protein. Rescued larvae arrest at the subsequent larval molt, suggesting that amon is also required for the second to third instar larval molt. Our data indicate that the amon proprotein convertase is required during embryogenesis and larval development in Drosophila and support the hypothesis that AMON acts to proteolytically process peptide hormones that regulate hatching, larval growth, and larval ecdysis.}, author = {Rayburn, Lowell Y and Gooding, Holly C and Choksi, Semil P and Maloney, Dhea and Kidd, Ambrose R and Daria Siekhaus and Bender, Michael}, journal = {Genetics}, number = {1}, pages = {227 -- 237}, publisher = {Genetics Society of America}, title = {{Amontillado, the Drosophila homolog of the prohormone processing protease PC2, is required during embryogenesis and early larval development}}, volume = {163}, year = {2003}, } @article{3150, abstract = {Tripartite G-protein-coupled receptors (GPCRs) represent one of the largest groups of signal transducers, transmitting signals from hormones, neuropeptides, odorants, food and light. Ligand-bound receptors catalyse GDP/GTP exchange on the G-protein α-subunit (Gα), leading to α-GTP separation from the βγ subunits and pathway activation. Activating mutations in the receptors or G proteins underlie many human diseases, including some cancers, dwarfism and premature puberty. Regulators of G-protein signalling (RGS proteins) are known to modulate the level and duration of ligand-induced signalling by accelerating the intrinsic GTPase activity of the Gα subunit, and thus reformation of the inactive GDP-bound Gα. Here we find that even in the absence of receptor, mutation of the RGS family member Sst2 (refs 6-9) permits spontaneous activation of the G-protein-coupled mating pathway in Saccharomyces cerevisiae at levels normally seen only in the presence of ligand. Our work demonstrates the occurence of spontaneous tripartite G-protein signalling in vivo and identifies a requirement for RGS proteins in preventing such receptor-independent activation.}, author = {Daria Siekhaus and Drubin, David G}, journal = {Nature Cell Biology}, number = {3}, pages = {231 -- 235}, publisher = {Nature Publishing Group}, title = {{Spontaneous receptor-independent heterotrimeric G-protein signalling in an RGS mutant}}, doi = {10.1038/ncb941}, volume = {5}, year = {2003}, } @article{3209, abstract = {We show that the fixed alphabet shortest common supersequence (SCS) and the fixed alphabet longest common subsequence (LCS) problems parameterized in the number of strings are W[1]-hard. Unless W[1]=FPT, this rules out the existence of algorithms with time complexity of O(f(k)nα) for those problems. Here n is the size of the problem instance, α is constant, k is the number of strings and f is any function of k. The fixed alphabet version of the LCS problem is of particular interest considering the importance of sequence comparison (e.g. multiple sequence alignment) in the fixed length alphabet world of DNA and protein sequences.}, author = {Krzysztof Pietrzak}, journal = {Journal of Computer and System Sciences}, number = {4}, pages = {757 -- 771}, publisher = {Elsevier}, title = {{On the parameterized complexity of the fixed alphabet shortest common supersequence and longest common subsequence problems}}, doi = {10.1016/S0022-0000(03)00078-3}, volume = {67}, year = {2003}, } @inproceedings{3210, abstract = {Luby and Rackoff showed how to construct a (super-)pseudo-random permutation {0,1}2n→ {0,1}2n from some number r of pseudo-random functions {0,1}n → {0,1}n. Their construction, motivated by DES, consists of a cascade of r Feistel permutations. A Feistel permutation 1for a pseudo-random function f is defined as (L, R) → (R,L ⊕ f (R)), where L and R are the left and right part of the input and ⊕ denotes bitwise XOR or, in this paper, any other group operation on {0,1}n. The only non-trivial step of the security proof consists of proving that the cascade of r Feistel permutations with independent uniform random functions {0,1}n → {0,1}n, denoted Ψ2nr is indistinguishable from a uniform random permutation {0,1}2n → {0,1}2n by any computationally unbounded adaptive distinguisher making at most O(2cn) combined chosen plaintext/ciphertext queries for any c < α, where a is a security parameter. Luby and Rackoff proved α = 1/2 for r = 4. A natural problem, proposed by Pieprzyk is to improve on α for larger r. The best known result, α = 3/4 for r = 6, is due to Patarin. In this paper we prove a = 1 -O(1/r), i.e., the trivial upper bound α = 1 can be approached. The proof uses some new techniques that can be of independent interest. }, author = {Maurer, Ueli M and Krzysztof Pietrzak}, pages = {544 -- 561}, publisher = {Springer}, title = {{The security of many round Luby Rackoff pseudo random permutations}}, doi = {10.1007/3-540-39200-9_34}, volume = {2656}, year = {2003}, }