@article{10381, abstract = {We study phase behaviour of lipid-bilayer vesicles functionalised by ligand–receptor complexes made of synthetic DNA by introducing a modelling framework and a dedicated experimental platform. In particular, we perform Monte Carlo simulations that combine a coarse grained description of the lipid bilayer with state of art analytical models for multivalent ligand–receptor interactions. Using density of state calculations, we derive the partition function in pairs of vesicles and compute the number of ligand–receptor bonds as a function of temperature. Numerical results are compared to microscopy and fluorimetry experiments on large unilamellar vesicles decorated by DNA linkers carrying complementary overhangs. We find that vesicle aggregation is suppressed when the total number of linkers falls below a threshold value. Within the model proposed here, this is due to the higher configurational costs required to form inter-vesicle bridges as compared to intra-vesicle loops, which are in turn related to membrane deformability. Our findings and our numerical/experimental methodologies are applicable to the rational design of liposomes used as functional materials and drug delivery applications, as well as to study inter-membrane interactions in living systems, such as cell adhesion.}, author = {Bachmann, Stephan Jan and Kotar, Jurij and Parolini, Lucia and Šarić, Anđela and Cicuta, Pietro and Di Michele, Lorenzo and Mognetti, Bortolo Matteo}, issn = {1744-6848}, journal = {Soft Matter}, keywords = {condensed matter physics, general chemistry}, number = {37}, pages = {7804--7817}, publisher = {Royal Society of Chemistry}, title = {{Melting transition in lipid vesicles functionalised by mobile DNA linkers}}, doi = {10.1039/c6sm01515h}, volume = {12}, year = {2016}, } @article{1057, abstract = {Far-field super-resolution fluorescence microscopy discerns fluorophores residing closer than the diffraction barrier by briefly transferring them in different (typically ON and OFF) states before detection. In coordinate-targeted super-resolution variants, such as stimulated emission depletion (STED) microscopy, this state difference is created by the intensity minima and maxima of an optical pattern, causing all fluorophores to assume the off state, for instance, except at the minima. Although strong spatial confinement of the on state enables high resolution, it also subjects the fluorophores to excess intensities and state cycles at the maxima. Here, we address these issues by driving the fluorophores into a second off state that is inert to the excess light. By using reversibly switchable fluorescent proteins as labels, our approach reduces bleaching and enhances resolution and contrast in live-cell STED microscopy. Using two or more transitions to off states is a useful strategy for augmenting the power of coordinate-targeted super-resolution microscopy.}, author = {Danzl, Johann G and Sidenstein, Sven and Gregor, Carola and Urban, Nicolai and Ilgen, Peter and Jakobs, Stefan and Hell, Stefan}, journal = {Nature Photonics}, number = {2}, pages = {122 -- 128}, publisher = {Nature Publishing Group}, title = {{Coordinate-targeted fluorescence nanoscopy with multiple off states}}, doi = {10.1038/nphoton.2015.266}, volume = {10}, year = {2016}, } @article{1059, abstract = {A range of bright and photostable rhodamines and carbopyronines with absorption maxima in the range of λ=500-630 nm were prepared, and enabled the specific labeling of cytoskeletal filaments using HaloTag technology followed by staining with 1 μm solutions of the dye-ligand conjugates. The synthesis, photophysical parameters, fluorogenic behavior, and structure-property relationships of the new dyes are discussed. Light microscopy with stimulated emission depletion (STED) provided one- and two-color images of living cells with an optical resolution of 40-60 nm.}, author = {Butkevich, Alexey and Mitronova, Gyuzel and Sidenstein, Sven and Klocke, Jessica and Kamin, Dirk and Meineke, Dirk and D'Este, Elisa and Kraemer, Philip and Danzl, Johann G and Belov, Vladimir and Hell, Stefan}, journal = {Angewandte Chemie - International Edition}, number = {10}, pages = {3290 -- 3294}, publisher = {Wiley-Blackwell}, title = {{Fluorescent rhodamines and fluorogenic carbopyronines for super-resolution STED microscopy in living cells}}, doi = {10.1002/anie.201511018}, volume = {55}, year = {2016}, } @article{1060, abstract = {Superresolution fluorescence microscopy of multiple fluorophores still requires development. Here we present simultaneous three-colour stimulated emission depletion (STED) nanoscopy relying on a single STED beam at 620 nm. Toggling the STED beam between two or more power levels ("multilevelSTEDv) optimizes resolution and contrast in all colour channels, which are intrinsically co-aligned and well separated. Three-colour recording is demonstrated by imaging the nanoscale cytoskeletal organization in cultured hippocampal neurons. The down to ∼35 nm resolution identified periodic actin/betaII spectrin lattices along dendrites and spines; however, at presynaptic and postsynaptic sites, these patterns were found to be absent. Both our multicolour scheme and the 620 nm STED line should be attractive for routine STED microscopy applications.}, author = {Sidenstein, Sven and D'Este, Elisa and Böhm, Marvin and Danzl, Johann G and Belov, Vladimir and Hell, Stefan}, journal = {Scientific Reports}, pages = {1 -- 8}, publisher = {Nature Publishing Group}, title = {{Multicolour multilevel STED nanoscopy of actin/spectrin organization at synapses}}, doi = {10.1038/srep26725}, volume = {6}, year = {2016}, } @inproceedings{1068, abstract = {Games on graphs provide the appropriate framework to study several central problems in computer science, such as verification and synthesis of reactive systems. One of the most basic objectives for games on graphs is the liveness (or Büchi) objective that given a target set of vertices requires that some vertex in the target set is visited infinitely often. We study generalized Büchi objectives (i.e., conjunction of liveness objectives), and implications between two generalized Büchi objectives (known as GR(1) objectives), that arise in numerous applications in computer-aided verification. We present improved algorithms and conditional super-linear lower bounds based on widely believed assumptions about the complexity of (A1) combinatorial Boolean matrix multiplication and (A2) CNF-SAT. We consider graph games with n vertices, m edges, and generalized Büchi objectives with k conjunctions. First, we present an algorithm with running time O(k*n^2), improving the previously known O(k*n*m) and O(k^2*n^2) worst-case bounds. Our algorithm is optimal for dense graphs under (A1). Second, we show that the basic algorithm for the problem is optimal for sparse graphs when the target sets have constant size under (A2). Finally, we consider GR(1) objectives, with k_1 conjunctions in the antecedent and k_2 conjunctions in the consequent, and present an O(k_1 k_2 n^{2.5})-time algorithm, improving the previously known O(k_1*k_2*n*m)-time algorithm for m > n^{1.5}. }, author = {Chatterjee, Krishnendu and Dvorák, Wolfgang and Henzinger, Monika H and Loitzenbauer, Veronika}, location = {Krakow, Poland}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Conditionally optimal algorithms for generalized Büchi Games}}, doi = {10.4230/LIPIcs.MFCS.2016.25}, volume = {58}, year = {2016}, } @inproceedings{1069, abstract = {The Continuous Skolem Problem asks whether a real-valued function satisfying a linear differen- tial equation has a zero in a given interval of real numbers. This is a fundamental reachability problem for continuous linear dynamical systems, such as linear hybrid automata and continuous- time Markov chains. Decidability of the problem is currently open – indeed decidability is open even for the sub-problem in which a zero is sought in a bounded interval. In this paper we show decidability of the bounded problem subject to Schanuel’s Conjecture, a unifying conjecture in transcendental number theory. We furthermore analyse the unbounded problem in terms of the frequencies of the differential equation, that is, the imaginary parts of the characteristic roots. We show that the unbounded problem can be reduced to the bounded problem if there is at most one rationally linearly independent frequency, or if there are two rationally linearly independent frequencies and all characteristic roots are simple. We complete the picture by showing that de- cidability of the unbounded problem in the case of two (or more) rationally linearly independent frequencies would entail a major new effectiveness result in Diophantine approximation, namely computability of the Diophantine-approximation types of all real algebraic numbers.}, author = {Chonev, Ventsislav K and Ouaknine, Joël and Worrell, James}, location = {Rome, Italy}, publisher = {Schloss Dagstuhl- Leibniz-Zentrum fur Informatik}, title = {{On the skolem problem for continuous linear dynamical systems}}, doi = {10.4230/LIPIcs.ICALP.2016.100}, volume = {55}, year = {2016}, } @inproceedings{1070, abstract = {We present a logic that extends CTL (Computation Tree Logic) with operators that express synchronization properties. A property is synchronized in a system if it holds in all paths of a certain length. The new logic is obtained by using the same path quantifiers and temporal operators as in CTL, but allowing a different order of the quantifiers. This small syntactic variation induces a logic that can express non-regular properties for which known extensions of MSO with equality of path length are undecidable. We show that our variant of CTL is decidable and that the model-checking problem is in Delta_3^P = P^{NP^NP}, and is DP-hard. We analogously consider quantifier exchange in extensions of CTL, and we present operators defined using basic operators of CTL* that express the occurrence of infinitely many synchronization points. We show that the model-checking problem remains in Delta_3^P. The distinguishing power of CTL and of our new logic coincide if the Next operator is allowed in the logics, thus the classical bisimulation quotient can be used for state-space reduction before model checking. }, author = {Chatterjee, Krishnendu and Doyen, Laurent}, location = {Rome, Italy}, publisher = {Schloss Dagstuhl- Leibniz-Zentrum fur Informatik}, title = {{Computation tree logic for synchronization properties}}, doi = {10.4230/LIPIcs.ICALP.2016.98}, volume = {55}, year = {2016}, } @inproceedings{1071, abstract = {We consider data-structures for answering reachability and distance queries on constant-treewidth graphs with n nodes, on the standard RAM computational model with wordsize W=Theta(log n). Our first contribution is a data-structure that after O(n) preprocessing time, allows (1) pair reachability queries in O(1) time; and (2) single-source reachability queries in O(n/log n) time. This is (asymptotically) optimal and is faster than DFS/BFS when answering more than a constant number of single-source queries. The data-structure uses at all times O(n) space. Our second contribution is a space-time tradeoff data-structure for distance queries. For any epsilon in [1/2,1], we provide a data-structure with polynomial preprocessing time that allows pair queries in O(n^{1-\epsilon} alpha(n)) time, where alpha is the inverse of the Ackermann function, and at all times uses O(n^epsilon) space. The input graph G is not considered in the space complexity. }, author = {Chatterjee, Krishnendu and Ibsen-Jensen, Rasmus and Pavlogiannis, Andreas}, location = {Aarhus, Denmark}, publisher = {Schloss Dagstuhl- Leibniz-Zentrum fur Informatik}, title = {{Optimal reachability and a space time tradeoff for distance queries in constant treewidth graphs}}, doi = {10.4230/LIPIcs.ESA.2016.28}, volume = {57}, year = {2016}, } @inproceedings{10746, abstract = {Vortex states in superconducting (SC) structures, their dynamics and ways to manipulate them are topics of great interest. We report a new method of magnetic force microscopy (MFM) that allows the study of vortex states in mesoscopic SC samples. For the case of a SC ring, which is biased to a half-integer flux quantum, the flux modulation through the ring caused by the motion of the magnetic tip drives the ring between two consecutive fluxoid states. The corresponding current switching in the ring produces strong position-dependent forces on the cantilever. In the regime where the frequency of the thermally activated jumps between fluxoid states is close to the frequency of the cantilever, large changes in the cantilever frequency and dissipation are observed. This effect may be understood as a stochastic resonance (SR) process. These changes in the cantilever’s mechanical properties are used to “image” the barrier energies between fluxoid states. Additionally, SR imaging of the barrier energies are used to study the effect of the locally applied magnetic field from the MFM tip on the barrier heights. We report the results of measurements for Al rings. Further, the same imaging technique can be applied to more sophisticated SC structures such as arrays of Josephson junctions.}, author = {Polshyn, Hryhoriy and Naibert, Tyler and Chua, Victor and Budakian, Raffi}, booktitle = {APS March Meeting 2016}, issn = {0003-0503}, location = {Baltimore, MD, United States}, number = {2}, publisher = {American Physical Society}, title = {{Study of vortex states and dynamics in mesoscopic superconducting samples with MFM}}, volume = {61}, year = {2016}, } @inproceedings{10747, abstract = {Vortex interactions are key to explaining the behavior of many two dimensional superconducting systems. We report on the development of a technique to locally probe vortex interactions in a 2D array of Josephson junctions. Scanning a magnetic tip attached to an ultra-soft cantilever over the array produces changes in the frequency of the cantilever along certain lines, forming geometric patterns in the scans. Different tip-surface separations and external magnetic fields produce a number of different patterns. These patterns correspond to tip locations in which two configurations of vortices in the lattice have degenerate energies. By imaging the locations of these degeneracies, information on the local vortex interactions may be obtained.}, author = {Naibert, Tyler and Polshyn, Hryhoriy and Wolin, Brian and Durkin, Malcolm and Garrido Menacho, Rita and Shem, Ian Mondragon and Chua, Victor and Hughes, Taylor and Mason, Nadya and Budakian, Raffi}, booktitle = {APS March Meeting 2016}, issn = {0003-0503}, location = {Baltimore, MD, United States}, number = {2}, publisher = {American Physical Society}, title = {{Stochastic resonance magnetic force microscopy imaging of Josephson arrays}}, volume = {61}, year = {2016}, } @article{1081, abstract = {The asymmetric localization of proteins in the plasma membrane domains of eukaryotic cells is a fundamental manifestation of cell polarity that is central to multicellular organization and developmental patterning. In plants, the mechanisms underlying the polar localization of cargo proteins are still largely unknown and appear to be fundamentally distinct from those operating in mammals. Here, we present a systematic, quantitative comparative analysis of the polar delivery and subcellular localization of proteins that characterize distinct polar plasma membrane domains in plant cells. The combination of microscopic analyses and computational modeling revealed a mechanistic framework common to diverse polar cargos and underlying the establishment and maintenance of apical, basal, and lateral polar domains in plant cells. This mechanism depends on the polar secretion, constitutive endocytic recycling, and restricted lateral diffusion of cargos within the plasma membrane. Moreover, our observations suggest that polar cargo distribution involves the individual protein potential to form clusters within the plasma membrane and interact with the extracellular matrix. Our observations provide insights into the shared cellular mechanisms of polar cargo delivery and polarity maintenance in plant cells.}, author = {Łangowski, Łukasz and Wabnik, Krzysztof T and Li, Hongjiang and Vanneste, Steffen and Naramoto, Satoshi and Tanaka, Hirokazu and Friml, Jirí}, journal = {Cell Discovery}, publisher = {Nature Publishing Group}, title = {{Cellular mechanisms for cargo delivery and polarity maintenance at different polar domains in plant cells}}, doi = {10.1038/celldisc.2016.18}, volume = {2}, year = {2016}, } @inproceedings{10810, abstract = {The main goal of the SCP-ECG standard is to address ECG data and related metadata structuring, semantics and syntax, with the objective of facilitating interoperability and thus supporting and promoting the exchange of the relevant information for unary and serial ECG diagnosis. Starting with version V3.0, the standard now also provides support for the storage of continuous, long-term ECG recordings and affords a repository for selected ECG sequences and the related metadata to accommodate stress tests, drug trials and protocol-based ECG recordings. The global and per-lead measurements sections have been extended and three new sections have been introduced for storing beat-by-beat and/or spike-by-spike measurements and annotations. The used terminology and the provided measurements and annotations have been harmonized with the ISO/IEEE 11073-10102 Annotated ECG standard. Emphasis has also been put on harmonizing the Universal Statement Codes with the CDISC and the categorized AHA statement codes and similarly the drug and implanted devices codes with the ATC and NASPE/BPEG codes. }, author = {Rubel, Paul and Pani, Danilo and Schlögl, Alois and Fayn, Jocelyne and Badilini, Fabio and Macfarlane, Peter and Varri, Alpo}, booktitle = {2016 Computing in Cardiology Conference}, issn = {2325-887X}, location = {Vancouver, Canada}, pages = {309--312}, publisher = {Computing in Cardiology}, title = {{SCP-ECG V3.0: An enhanced standard communication protocol for computer-assisted electrocardiography}}, doi = {10.22489/cinc.2016.090-500}, volume = {43}, year = {2016}, } @article{9456, abstract = {The discovery of introns four decades ago was one of the most unexpected findings in molecular biology. Introns are sequences interrupting genes that must be removed as part of messenger RNA production. Genome sequencing projects have shown that most eukaryotic genes contain at least one intron, and frequently many. Comparison of these genomes reveals a history of long evolutionary periods during which few introns were gained, punctuated by episodes of rapid, extensive gain. However, although several detailed mechanisms for such episodic intron generation have been proposed, none has been empirically supported on a genomic scale. Here we show how short, non-autonomous DNA transposons independently generated hundreds to thousands of introns in the prasinophyte Micromonas pusilla and the pelagophyte Aureococcus anophagefferens. Each transposon carries one splice site. The other splice site is co-opted from the gene sequence that is duplicated upon transposon insertion, allowing perfect splicing out of the RNA. The distributions of sequences that can be co-opted are biased with respect to codons, and phasing of transposon-generated introns is similarly biased. These transposons insert between pre-existing nucleosomes, so that multiple nearby insertions generate nucleosome-sized intervening segments. Thus, transposon insertion and sequence co-option may explain the intron phase biases and prevalence of nucleosome-sized exons observed in eukaryotes. Overall, the two independent examples of proliferating elements illustrate a general DNA transposon mechanism that can plausibly account for episodes of rapid, extensive intron gain during eukaryotic evolution.}, author = {Huff, Jason T. and Zilberman, Daniel and Roy, Scott W.}, issn = {1476-4687}, journal = {Nature}, number = {7626}, pages = {533--536}, publisher = {Springer Nature }, title = {{Mechanism for DNA transposons to generate introns on genomic scales}}, doi = {10.1038/nature20110}, volume = {538}, year = {2016}, } @article{9473, abstract = {Cytosine DNA methylation regulates the expression of eukaryotic genes and transposons. Methylation is copied by methyltransferases after DNA replication, which results in faithful transmission of methylation patterns during cell division and, at least in flowering plants, across generations. Transgenerational inheritance is mediated by a small group of cells that includes gametes and their progenitors. However, methylation is usually analyzed in somatic tissues that do not contribute to the next generation, and the mechanisms of transgenerational inheritance are inferred from such studies. To gain a better understanding of how DNA methylation is inherited, we analyzed purified Arabidopsis thaliana sperm and vegetative cells-the cell types that comprise pollen-with mutations in the DRM, CMT2, and CMT3 methyltransferases. We find that DNA methylation dependency on these enzymes is similar in sperm, vegetative cells, and somatic tissues, although DRM activity extends into heterochromatin in vegetative cells, likely reflecting transcription of heterochromatic transposons in this cell type. We also show that lack of histone H1, which elevates heterochromatic DNA methylation in somatic tissues, does not have this effect in pollen. Instead, levels of CG methylation in wild-type sperm and vegetative cells, as well as in wild-type microspores from which both pollen cell types originate, are substantially higher than in wild-type somatic tissues and similar to those of H1-depleted roots. Our results demonstrate that the mechanisms of methylation maintenance are similar between pollen and somatic cells, but the efficiency of CG methylation is higher in pollen, allowing methylation patterns to be accurately inherited across generations.}, author = {Hsieh, Ping-Hung and He, Shengbo and Buttress, Toby and Gao, Hongbo and Couchman, Matthew and Fischer, Robert L. and Zilberman, Daniel and Feng, Xiaoqi}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {52}, pages = {15132--15137}, publisher = {National Academy of Sciences}, title = {{Arabidopsis male sexual lineage exhibits more robust maintenance of CG methylation than somatic tissues}}, doi = {10.1073/pnas.1619074114}, volume = {113}, year = {2016}, } @article{9477, abstract = {Cytosine methylation is a DNA modification with important regulatory functions in eukaryotes. In flowering plants, sexual reproduction is accompanied by extensive DNA demethylation, which is required for proper gene expression in the endosperm, a nutritive extraembryonic seed tissue. Endosperm arises from a fusion of a sperm cell carried in the pollen and a female central cell. Endosperm DNA demethylation is observed specifically on the chromosomes inherited from the central cell in Arabidopsis thaliana, rice, and maize, and requires the DEMETER DNA demethylase in Arabidopsis. DEMETER is expressed in the central cell before fertilization, suggesting that endosperm demethylation patterns are inherited from the central cell. Down-regulation of the MET1 DNA methyltransferase has also been proposed to contribute to central cell demethylation. However, with the exception of three maize genes, central cell DNA methylation has not been directly measured, leaving the origin and mechanism of endosperm demethylation uncertain. Here, we report genome-wide analysis of DNA methylation in the central cells of Arabidopsis and rice—species that diverged 150 million years ago—as well as in rice egg cells. We find that DNA demethylation in both species is initiated in central cells, which requires DEMETER in Arabidopsis. However, we do not observe a global reduction of CG methylation that would be indicative of lowered MET1 activity; on the contrary, CG methylation efficiency is elevated in female gametes compared with nonsexual tissues. Our results demonstrate that locus-specific, active DNA demethylation in the central cell is the origin of maternal chromosome hypomethylation in the endosperm.}, author = {Park, Kyunghyuk and Kim, M. Yvonne and Vickers, Martin and Park, Jin-Sup and Hyun, Youbong and Okamoto, Takashi and Zilberman, Daniel and Fischer, Robert L. and Feng, Xiaoqi and Choi, Yeonhee and Scholten, Stefan}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {Multidisciplinary}, number = {52}, pages = {15138--15143}, publisher = {National Academy of Sciences}, title = {{DNA demethylation is initiated in the central cells of Arabidopsis and rice}}, doi = {10.1073/pnas.1619047114}, volume = {113}, year = {2016}, } @inproceedings{948, abstract = {Experience constantly shapes neural circuits through a variety of plasticity mechanisms. While the functional roles of some plasticity mechanisms are well-understood, it remains unclear how changes in neural excitability contribute to learning. Here, we develop a normative interpretation of intrinsic plasticity (IP) as a key component of unsupervised learning. We introduce a novel generative mixture model that accounts for the class-specific statistics of stimulus intensities, and we derive a neural circuit that learns the input classes and their intensities. We will analytically show that inference and learning for our generative model can be achieved by a neural circuit with intensity-sensitive neurons equipped with a specific form of IP. Numerical experiments verify our analytical derivations and show robust behavior for artificial and natural stimuli. Our results link IP to non-trivial input statistics, in particular the statistics of stimulus intensities for classes to which a neuron is sensitive. More generally, our work paves the way toward new classification algorithms that are robust to intensity variations.}, author = {Monk, Travis and Savin, Cristina and Lücke, Jörg}, location = {Barcelona, Spaine}, pages = {4285 -- 4293}, publisher = {Neural Information Processing Systems}, title = {{Neurons equipped with intrinsic plasticity learn stimulus intensity statistics}}, volume = {29}, year = {2016}, } @article{9591, abstract = {We give several results showing that different discrete structures typically gain certain spanning substructures (in particular, Hamilton cycles) after a modest random perturbation. First, we prove that adding linearly many random edges to a dense k-uniform hypergraph ensures the (asymptotically almost sure) existence of a perfect matching or a loose Hamilton cycle. The proof involves an interesting application of Szemerédi's Regularity Lemma, which might be independently useful. We next prove that digraphs with certain strong expansion properties are pancyclic, and use this to show that adding a linear number of random edges typically makes a dense digraph pancyclic. Finally, we prove that perturbing a certain (minimum-degree-dependent) number of random edges in a tournament typically ensures the existence of multiple edge-disjoint Hamilton cycles. All our results are tight.}, author = {Krivelevich, Michael and Kwan, Matthew Alan and Sudakov, Benny}, issn = {1469-2163}, journal = {Combinatorics, Probability and Computing}, number = {6}, pages = {909--927}, publisher = {Cambridge University Press}, title = {{Cycles and matchings in randomly perturbed digraphs and hypergraphs}}, doi = {10.1017/s0963548316000079}, volume = {25}, year = {2016}, } @article{9654, abstract = {RNA polymerase I (Pol I) is a highly processive enzyme that transcribes ribosomal DNA (rDNA) and regulates growth of eukaryotic cells. Crystal structures of free Pol I from the yeast Saccharomyces cerevisiae have revealed dimers of the enzyme stabilized by a 'connector' element and an expanded cleft containing the active centre in an inactive conformation. The central bridge helix was unfolded and a Pol-I-specific 'expander' element occupied the DNA-template-binding site. The structure of Pol I in its active transcribing conformation has yet to be determined, whereas structures of Pol II and Pol III have been solved with bound DNA template and RNA transcript. Here we report structures of active transcribing Pol I from yeast solved by two different cryo-electron microscopy approaches. A single-particle structure at 3.8 Å resolution reveals a contracted active centre cleft with bound DNA and RNA, and a narrowed pore beneath the active site that no longer holds the RNA-cleavage-stimulating domain of subunit A12.2. A structure at 29 Å resolution that was determined from cryo-electron tomograms of Pol I enzymes transcribing cellular rDNA confirms contraction of the cleft and reveals that incoming and exiting rDNA enclose an angle of around 150°. The structures suggest a model for the regulation of transcription elongation in which contracted and expanded polymerase conformations are associated with active and inactive states, respectively.}, author = {Neyer, Simon and Kunz, Michael and Geiss, Christian and Hantsche, Merle and Hodirnau, Victor-Valentin and Seybert, Anja and Engel, Christoph and Scheffer, Margot P. and Cramer, Patrick and Frangakis, Achilleas S.}, issn = {1476-4687}, journal = {Nature}, number = {7634}, pages = {607--610}, publisher = {Springer Nature}, title = {{Structure of RNA polymerase I transcribing ribosomal DNA genes}}, doi = {10.1038/nature20561}, volume = {540}, year = {2016}, } @article{9681, abstract = {One of the most prominent consequences of the quantum nature of light atomic nuclei is that their kinetic energy does not follow a Maxwell–Boltzmann distribution. Deep inelastic neutron scattering (DINS) experiments can measure this effect. Thus, the nuclear quantum kinetic energy can be probed directly in both ordered and disordered samples. However, the relation between the quantum kinetic energy and the atomic environment is a very indirect one, and cross-validation with theoretical modeling is therefore urgently needed. Here, we use state of the art path integral molecular dynamics techniques to compute the kinetic energy of hydrogen and oxygen nuclei in liquid, solid, and gas-phase water close to the triple point, comparing three different interatomic potentials and validating our results against equilibrium isotope fractionation measurements. We will then show how accurate simulations can draw a link between extremely precise fractionation experiments and DINS, therefore establishing a reliable benchmark for future measurements and providing key insights to increase further the accuracy of interatomic potentials for water.}, author = {Cheng, Bingqing and Behler, Jörg and Ceriotti, Michele}, issn = {1948-7185}, journal = {The Journal of Physical Chemistry Letters}, number = {12}, pages = {2210--2215}, publisher = {American Chemical Society}, title = {{Nuclear quantum effects in water at the triple point: Using theory as a link between experiments}}, doi = {10.1021/acs.jpclett.6b00729}, volume = {7}, year = {2016}, } @misc{9704, abstract = {Emerging infectious diseases (EIDs) have contributed significantly to the current biodiversity crisis, leading to widespread epidemics and population loss. Owing to genetic variation in pathogen virulence, a complete understanding of species decline requires the accurate identification and characterization of EIDs. We explore this issue in the Western honeybee, where increasing mortality of populations in the Northern Hemisphere has caused major concern. Specifically, we investigate the importance of genetic identity of the main suspect in mortality, deformed wing virus (DWV), in driving honeybee loss. Using laboratory experiments and a systematic field survey, we demonstrate that an emerging DWV genotype (DWV-B) is more virulent than the established DWV genotype (DWV-A) and is widespread in the landscape. Furthermore, we show in a simple model that colonies infected with DWV-B collapse sooner than colonies infected with DWV-A. We also identify potential for rapid DWV evolution by revealing extensive genome-wide recombination in vivo. The emergence of DWV-B in naive honeybee populations, including via recombination with DWV-A, could be of significant ecological and economic importance. Our findings emphasize that knowledge of pathogen genetic identity and diversity is critical to understanding drivers of species decline.}, author = {Mcmahon, Dino and Natsopoulou, Myrsini and Doublet, Vincent and Fürst, Matthias and Weging, Silvio and Brown, Mark and Gogol Döring, Andreas and Paxton, Robert}, publisher = {Dryad}, title = {{Data from: Elevated virulence of an emerging viral genotype as a driver of honeybee loss}}, doi = {10.5061/dryad.cq7t1}, year = {2016}, }