@article{11103, abstract = {Over the last decade, the nuclear envelope (NE) has emerged as a key component in the organization and function of the nuclear genome. As many as 100 different proteins are thought to specifically localize to this double membrane that separates the cytoplasm and the nucleoplasm of eukaryotic cells. Selective portals through the NE are formed at sites where the inner and outer nuclear membranes are fused, and the coincident assembly of ∼30 proteins into nuclear pore complexes occurs. These nuclear pore complexes are essential for the control of nucleocytoplasmic exchange. Many of the NE and nuclear pore proteins are thought to play crucial roles in gene regulation and thus are increasingly linked to human diseases.}, author = {HETZER, Martin W and Wente, Susan R.}, issn = {1534-5807}, journal = {Developmental Cell}, keywords = {Developmental Biology, Cell Biology, General Biochemistry, Genetics and Molecular Biology, Molecular Biology}, number = {5}, pages = {606--616}, publisher = {Elsevier}, title = {{Border control at the nucleus: Biogenesis and organization of the nuclear membrane and pore complexes}}, doi = {10.1016/j.devcel.2009.10.007}, volume = {17}, year = {2009}, } @article{11105, abstract = {Nuclear-pore complexes (NPCs) are large protein channels that span the nuclear envelope (NE), which is a double membrane that encloses the nuclear genome of eukaryotes. Each of the typically 2,000–4,000 pores in the NE of vertebrate cells is composed of multiple copies of 30 different proteins known as nucleoporins. The evolutionarily conserved NPC proteins have the well-characterized function of mediating the transport of molecules between the nucleoplasm and the cytoplasm. Mutations in nucleoporins are often linked to specific developmental defects and disease, and the resulting phenotypes are usually interpreted as the consequences of perturbed nuclear transport activity. However, recent evidence suggests that NPCs have additional functions in chromatin organization and gene regulation, some of which might be independent of nuclear transport. Here, we review the transport-dependent and transport-independent roles of NPCs in the regulation of nuclear function and gene expression.}, author = {Capelson, Maya and HETZER, Martin W}, issn = {1469-3178}, journal = {EMBO reports}, keywords = {Genetics, Molecular Biology, Biochemistry}, number = {7}, pages = {697--705}, publisher = {EMBO}, title = {{The role of nuclear pores in gene regulation, development and disease}}, doi = {10.1038/embor.2009.147}, volume = {10}, year = {2009}, } @article{11106, abstract = {Formation of the nuclear envelope (NE) around segregated chromosomes occurs by the reshaping of the endoplasmic reticulum (ER), a reservoir for disassembled nuclear membrane components during mitosis. In this study, we show that inner nuclear membrane proteins such as lamin B receptor (LBR), MAN1, Lap2β, and the trans-membrane nucleoporins Ndc1 and POM121 drive the spreading of ER membranes into the emerging NE via their capacity to bind chromatin in a collaborative manner. Despite their redundant functions, decreasing the levels of any of these trans-membrane proteins by RNAi-mediated knockdown delayed NE formation, whereas increasing the levels of any of them had the opposite effect. Furthermore, acceleration of NE formation interferes with chromosome separation during mitosis, indicating that the time frame over which chromatin becomes membrane enclosed is physiologically relevant and regulated. These data suggest that functionally distinct classes of chromatin-interacting membrane proteins, which are present at nonsaturating levels, collaborate to rapidly reestablish the nuclear compartment at the end of mitosis.}, author = {Anderson, Daniel J. and Vargas, Jesse D. and Hsiao, Joshua P. and HETZER, Martin W}, issn = {1540-8140}, journal = {Journal of Cell Biology}, keywords = {Cell Biology}, number = {2}, pages = {183--191}, publisher = {Rockefeller University Press}, title = {{Recruitment of functionally distinct membrane proteins to chromatin mediates nuclear envelope formation in vivo}}, doi = {10.1083/jcb.200901106}, volume = {186}, year = {2009}, } @article{11107, abstract = {Nucleocytoplasmic transport occurs exclusively through nuclear pore complexes (NPCs) embedded in pores formed by inner and outer nuclear membrane fusion. The mechanism for de novo pore and NPC biogenesis remains unclear. Reticulons (RTNs) and Yop1/DP1 are conserved membrane protein families required to form and maintain the tubular endoplasmic reticulum (ER) and the postmitotic nuclear envelope. In this study, we report that members of the RTN and Yop1/DP1 families are required for nuclear pore formation. Analysis of Saccharomyces cerevisiae prp20-G282S and nup133Δ NPC assembly mutants revealed perturbations in Rtn1–green fluorescent protein (GFP) and Yop1-GFP ER distribution and colocalization to NPC clusters. Combined deletion of RTN1 and YOP1 resulted in NPC clustering, nuclear import defects, and synthetic lethality with the additional absence of Pom34, Pom152, and Nup84 subcomplex members. We tested for a direct role in NPC biogenesis using Xenopus laevis in vitro assays and found that anti-Rtn4a antibodies specifically inhibited de novo nuclear pore formation. We hypothesize that these ER membrane–bending proteins mediate early NPC assembly steps.}, author = {Dawson, T. Renee and Lazarus, Michelle D. and HETZER, Martin W and Wente, Susan R.}, issn = {1540-8140}, journal = {Journal of Cell Biology}, keywords = {Cell Biology}, number = {5}, pages = {659--675}, publisher = {Rockefeller University Press}, title = {{ER membrane–bending proteins are necessary for de novo nuclear pore formation}}, doi = {10.1083/jcb.200806174}, volume = {184}, year = {2009}, } @article{11108, abstract = {In dividing cells, nuclear pore complexes (NPCs) disassemble during mitosis and reassemble into the newly forming nuclei. However, the fate of nuclear pores in postmitotic cells is unknown. Here, we show that NPCs, unlike other nuclear structures, do not turn over in differentiated cells. While a subset of NPC components, like Nup153 and Nup50, are continuously exchanged, scaffold nucleoporins, like the Nup107/160 complex, are extremely long-lived and remain incorporated in the nuclear membrane during the entire cellular life span. Besides the lack of nucleoporin expression and NPC turnover, we discovered an age-related deterioration of NPCs, leading to an increase in nuclear permeability and the leaking of cytoplasmic proteins into the nucleus. Our finding that nuclear “leakiness” is dramatically accelerated during aging and that a subset of nucleoporins is oxidatively damaged in old cells suggests that the accumulation of damage at the NPC might be a crucial aging event.}, author = {D'Angelo, Maximiliano A. and Raices, Marcela and Panowski, Siler H. and HETZER, Martin W}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {2}, pages = {284--295}, publisher = {Elsevier}, title = {{Age-dependent deterioration of nuclear pore complexes causes a loss of nuclear integrity in postmitotic cells}}, doi = {10.1016/j.cell.2008.11.037}, volume = {136}, year = {2009}, } @inproceedings{11752, abstract = {We propose a model which suggests that structural martensitic transitions are related to significant changes in the electronic structure, and are effected by high-magnetic fields. The magnetic field dependence is considered unusual as many influential investigations of martensitic transitions have emphasized that the structural transitions are primarily lattice dynamical and are driven by the entropy due to the phonons. We provide a theoretical framework which can be used to describe the effect of high magnetic field on the transition and lattice dynamics in which the field dependence originates from the dielectric constant. The model is compared with some recent experimental results.}, author = {Yang, Xiaodong and Riseborough, Peter S and Modic, Kimberly A and Fisher, R A and Oppeil, C P and Finlayson, T R and Cooley, J C and Smith, J L and Goddard, P A and Silhanek, A V and Lashley, J C}, booktitle = {Journal of Physics: Conference Series}, issn = {1742-6596}, location = {Karlsruhe, Germany}, number = {3}, publisher = {IOP Publishing}, title = {{Influence of magnetic fields on structural martensitic transitions}}, doi = {10.1088/1742-6596/200/3/032062}, volume = {200}, year = {2009}, } @article{8026, abstract = {Recent theoretical work has provided a basic understanding of signal propagation in networks of spiking neurons, but mechanisms for gating and controlling these signals have not been investigated previously. Here we introduce an idea for the gating of multiple signals in cortical networks that combines principles of signal propagation with aspects of balanced networks. Specifically, we studied networks in which incoming excitatory signals are normally cancelled by locally evoked inhibition, leaving the targeted layer unresponsive. Transmission can be gated 'on' by modulating excitatory and inhibitory gains to upset this detailed balance. We illustrate gating through detailed balance in large networks of integrate-and-fire neurons. We show successful gating of multiple signals and study failure modes that produce effects reminiscent of clinically observed pathologies. Provided that the individual signals are detectable, detailed balance has a large capacity for gating multiple signals.}, author = {Vogels, Tim P and Abbott, L F}, issn = {1097-6256}, journal = {Nature Neuroscience}, number = {4}, pages = {483--491}, publisher = {Springer Nature}, title = {{Gating multiple signals through detailed balance of excitation and inhibition in spiking networks}}, doi = {10.1038/nn.2276}, volume = {12}, year = {2009}, } @article{8474, abstract = {Hydrogen bonds are ubiquitous interactions in proteins, and are important for their folding and functionality. Scalar coupling constants across hydrogen bonds in the protein backbone, some as small as 0.5 Hz, can be directly measured in the solid state by NMR spectroscopy (see figure). The nuclei on both sides of the hydrogen bond can be identified and the size of the coupling constant can be measured accurately.}, author = {Schanda, Paul and Huber, Matthias and Verel, René and Ernst, Matthias and Meier, Beat H.}, issn = {1433-7851}, journal = {Angewandte Chemie International Edition}, keywords = {General Chemistry, Catalysis}, number = {49}, pages = {9322--9325}, publisher = {Wiley}, title = {{Direct detection of 3hJN' hydrogen-bond scalar couplings in proteins by solid-state NMR spectroscopy}}, doi = {10.1002/anie.200904411}, volume = {48}, year = {2009}, } @article{8475, author = {Schanda, Paul}, issn = {0079-6565}, journal = {Progress in Nuclear Magnetic Resonance Spectroscopy}, number = {3}, pages = {238--265}, publisher = {Elsevier}, title = {{Fast-pulsing longitudinal relaxation optimized techniques: Enriching the toolbox of fast biomolecular NMR spectroscopy}}, doi = {10.1016/j.pnmrs.2009.05.002}, volume = {55}, year = {2009}, } @article{8476, abstract = {Atomic-resolution information on the structure and dynamics of nucleic acids is essential for a better understanding of the mechanistic basis of many cellular processes. NMR spectroscopy is a powerful method for studying the structure and dynamics of nucleic acids; however, solution NMR studies are currently limited to relatively small nucleic acids at high concentrations. Thus, technological and methodological improvements that increase the experimental sensitivity and spectral resolution of NMR spectroscopy are required for studies of larger nucleic acids or protein−nucleic acid complexes. Here we introduce a series of imino-proton-detected NMR experiments that yield an over 2-fold increase in sensitivity compared to conventional pulse schemes. These methods can be applied to the detection of base pair interactions, RNA−ligand titration experiments, measurement of residual dipolar 15N−1H couplings, and direct measurements of conformational transitions. These NMR experiments employ longitudinal spin relaxation enhancement techniques that have proven useful in protein NMR spectroscopy. The performance of these new experiments is demonstrated for a 10 kDa TAR-TAR*GA RNA kissing complex and a 26 kDa tRNA.}, author = {Farjon, Jonathan and Boisbouvier, Jérôme and Schanda, Paul and Pardi, Arthur and Simorre, Jean-Pierre and Brutscher, Bernhard}, issn = {0002-7863}, journal = {Journal of the American Chemical Society}, number = {24}, pages = {8571--8577}, publisher = {American Chemical Society}, title = {{Longitudinal-relaxation-enhanced NMR experiments for the study of nucleic acids in solution}}, doi = {10.1021/ja901633y}, volume = {131}, year = {2009}, } @article{8477, abstract = {An optimized NMR experiment that combines the advantages of methyl-TROSY and SOFAST-HMQC has been developed. It allows the recording of high quality methyl 1H−13C correlation spectra of protein assemblies of several hundreds of kDa in a few seconds. The SOFAST-methyl-TROSY-based experiment offers completely new opportunities for the study of structural and dynamic changes occurring in molecular nanomachines while they perform their biological function in vitro.}, author = {Amero, Carlos and Schanda, Paul and Durá, M. Asunción and Ayala, Isabel and Marion, Dominique and Franzetti, Bruno and Brutscher, Bernhard and Boisbouvier, Jérôme}, issn = {0002-7863}, journal = {Journal of the American Chemical Society}, number = {10}, pages = {3448--3449}, publisher = {American Chemical Society}, title = {{Fast two-dimensional NMR spectroscopy of high molecular weight protein assemblies}}, doi = {10.1021/ja809880p}, volume = {131}, year = {2009}, } @article{8478, abstract = {Allosteric regulation is an effective mechanism of control in biological processes. In allosteric proteins a signal originating at one site in the molecule is communicated through the protein structure to trigger a specific response at a remote site. Using NMR relaxation dispersion techniques we directly observe the dynamic process through which the KIX domain of CREB binding protein communicates allosteric information between binding sites. KIX mediates cooperativity between pairs of transcription factors through binding to two distinct interaction surfaces in an allosteric manner. We show that binding the activation domain of the mixed lineage leukemia (MLL) transcription factor to KIX induces a redistribution of the relative populations of KIX conformations toward a high-energy state in which the allosterically activated second binding site is already preformed, consistent with the Monod−Wyman−Changeux (WMC) model of allostery. The structural rearrangement process that links the two conformers and by which allosteric information is communicated occurs with a time constant of 3 ms at 27 °C. Our dynamic NMR data reveal that an evolutionarily conserved network of hydrophobic amino acids constitutes the pathway through which information is transmitted.}, author = {Brüschweiler, Sven and Schanda, Paul and Kloiber, Karin and Brutscher, Bernhard and Kontaxis, Georg and Konrat, Robert and Tollinger, Martin}, issn = {0002-7863}, journal = {Journal of the American Chemical Society}, number = {8}, pages = {3063--3068}, publisher = {American Chemical Society}, title = {{Direct observation of the dynamic process underlying allosteric signal transmission}}, doi = {10.1021/ja809947w}, volume = {131}, year = {2009}, } @article{8479, abstract = {Multidimensional NMR spectroscopy is a well-established technique for the characterization of structure and fast-time-scale dynamics of highly populated ground states of biological macromolecules. The investigation of short-lived excited states that are important for molecular folding, misfolding and function, however, remains a challenge for modern biomolecular NMR techniques. Off-equilibrium real-time kinetic NMR methods allow direct observation of conformational or chemical changes by following peak positions and intensities in a series of spectra recorded during a kinetic event. Because standard multidimensional NMR methods required to yield sufficient atom-resolution are intrinsically time-consuming, many interesting phenomena are excluded from real-time NMR analysis. Recently, spatially encoded ultrafast 2D NMR techniques have been proposed that allow one to acquire a 2D NMR experiment within a single transient. In addition, when combined with the SOFAST technique, such ultrafast experiments can be repeated at high rates. One of the problems detected for such ultrafast protein NMR experiments is related to the heteronuclear decoupling during detection with interferences between the pulses and the oscillatory magnetic field gradients arising in this scheme. Here we present a method for improved ultrafast data acquisition yielding higher signal to noise and sharper lines in single-scan 2D NMR spectra. In combination with a fast-mixing device, the recording of 1H–15N correlation spectra with repetition rates of up to a few Hertz becomes feasible, enabling real-time studies of protein kinetics occurring on time scales down to a few seconds.}, author = {Gal, Maayan and Kern, Thomas and Schanda, Paul and Frydman, Lucio and Brutscher, Bernhard}, issn = {0925-2738}, journal = {Journal of Biomolecular NMR}, keywords = {Spectroscopy, Biochemistry}, pages = {1--10}, publisher = {Springer Nature}, title = {{An improved ultrafast 2D NMR experiment: Towards atom-resolved real-time studies of protein kinetics at multi-Hz rates}}, doi = {10.1007/s10858-008-9284-9}, volume = {43}, year = {2009}, } @article{8508, abstract = {We study generic unfoldings of homoclinic tangencies of two-dimensional area-preserving diffeomorphisms (conservative New house phenomena) and show that they give rise to invariant hyperbolic sets of arbitrarily large Hausdorff dimension. As applications, we discuss the size of the stochastic layer of a standard map and the Hausdorff dimension of invariant hyperbolic sets for certain restricted three-body problems. We avoid involved technical details and only concentrate on the ideas of the proof of the presented results.}, author = {Gorodetski, Anton and Kaloshin, Vadim}, issn = {0081-5438}, journal = {Proceedings of the Steklov Institute of Mathematics}, keywords = {Mathematics (miscellaneous)}, number = {1}, pages = {76--90}, publisher = {Springer Nature}, title = {{Conservative homoclinic bifurcations and some applications}}, doi = {10.1134/s0081543809040063}, volume = {267}, year = {2009}, } @article{88, abstract = {We have developed a tunable source of Mie scale microdroplet aerosols that can be used for the generation of energetic ions. To demonstrate this potential, a terawatt Ti: Al2 O3 laser focused to 2×10 19 W/cm2 was used to irradiate heavy water (D2 O) aerosols composed of micron-scale droplets. Energetic deuterium ions, which were generated in the laser-droplet interaction, produced deuterium-deuterium fusion with approximately 2×10^3 fusion neutrons measured per joule of incident laser energy. }, author = {Higginbotham, Andrew P and Semonin, Octavi and Bruce, S and Chan, C and Maindi, M and Donnelly, Tom and Maurer, M and Bang, Woosuk and Churina, I.V and Osterholz, Jens and Kim, I and Bernstein, Aaron and Ditmire, Todd}, journal = {Review of Scientific Instruments}, number = {6}, publisher = {American Institute of Physics}, title = {{Generation of Mie size microdroplet aerosols with applications in laser-driven fusion experiments}}, doi = {10.1063/1.3155302}, volume = {80}, year = {2009}, } @inbook{164, abstract = {Let g be a cubic polynomial with integer coefficients and n>9 variables, and assume that the congruence g=0 modulo p^k is soluble for all prime powers p^k. We show that the equation g=0 has infinitely many integer solutions when the cubic part of g defines a projective hypersurface with singular locus of dimension <n-10. The proof is based on the Hardy-Littlewood circle method.}, author = {Browning, Timothy D and Heath Brown, Roger}, booktitle = {Analytic Number Theory: Essays in honour of Klaus Roth}, pages = {75 -- 90}, publisher = {Cambridge University Press}, title = {{Integral points on cubic hypersurfaces}}, year = {2009}, } @inproceedings{165, abstract = {We survey the state of affairs for the distribution of ℚ-rational points on non-singular del Pezzo surfaces of low degree, highlighting the recent resolution of Manin's conjecture for a non-singular del Pezzo surface of degree 4 by la Bretèche and Browning.}, author = {Timothy Browning}, editor = {Aoki, Takashi and Kanemitsu, Shigeru and Liu, Jianya}, pages = {1 -- 18}, publisher = {World Scientific Publishing}, title = {{Resent progress on the quantitative arithmetic of del Pezzo surfaces}}, doi = {https://doi.org/10.1142/9789814289924_0001}, volume = {6}, year = {2009}, } @inbook{168, abstract = {The arithmetic of ternary diagonal equation is considered for degree d >1, with the outcome that the set of coefficients for which the equation admits a non-zero integer solution is shown to have density zero.}, author = {Timothy Browning and Dietmann, Rainer}, booktitle = {Quadratic Forms - algebra, arithmetic and geometry}, pages = {99 -- 106}, publisher = {American Mathematical Society}, title = {{Solubility of Fermat equations}}, doi = {http://dx.doi.org/10.1090/conm/493}, volume = {493}, year = {2009}, } @article{1718, abstract = {Morphogens act as graded positional cues to control cell fate specification in many developing tissues. This concept, in which a signaling gradient regulates differential gene expression in a concentration-dependent manner, has received considerable experimental support. Nevertheless, several recent studies have challenged the straightforward model of morphogen activity. In particular, the observation that pattern formation is a dynamic process has raised questions about the influence of time on morphogen activity. Here we propose that the spatiotemporal dynamics of the cellular response to a morphogen gradient depend on a combination of temporal alterations to the morphogen gradient itself, the dynamics of its signal transduction and downstream interactions between target genes.}, author = {Kutějová, Eva and Briscoe, James and Anna Kicheva}, journal = {Current Opinion in Genetics & Development}, number = {4}, pages = {315 -- 322}, publisher = {Elsevier}, title = {{Temporal dynamics of patterning by morphogen gradients}}, doi = {10.1016/j.gde.2009.05.004}, volume = {19}, year = {2009}, } @article{1720, abstract = {How morphogen gradients are formed in target tissues is a key question for understanding the mechanisms of morphological patterning. Here, we review different mechanisms of morphogen gradient formation from theoretical and experimental points of view. First, a simple, comprehensive overview of the underlying biophysical principles of several mechanisms of gradient formation is provided. We then discuss the advantages and limitations of different experimental approaches to gradient formation analysis.}, author = {Wartlick, Ortrud and Anna Kicheva and González-Gaitán, Marcos A}, journal = {Cold Spring Harbor perspectives in biology}, number = {3}, publisher = {Cold Spring Harbor Laboratory Press}, title = {{Morphogen gradient formation }}, doi = {10.1101/cshperspect.a001255}, volume = {1}, year = {2009}, }