@article{8466, abstract = {Recent advances in NMR spectroscopy and the availability of high magnetic field strengths now offer the possibility to record real-time 3D NMR spectra of short-lived protein states, e.g., states that become transiently populated during protein folding. Here we present a strategy for obtaining sequential NMR assignments as well as atom-resolved information on structural and dynamic features within a folding intermediate of the amyloidogenic protein β2-microglobulin that has a half-lifetime of only 20 min.}, author = {Rennella, Enrico and Cutuil, Thomas and Schanda, Paul and Ayala, Isabel and Forge, Vincent and Brutscher, Bernhard}, issn = {0002-7863}, journal = {Journal of the American Chemical Society}, number = {19}, pages = {8066--8069}, publisher = {American Chemical Society}, title = {{Real-time NMR characterization of structure and dynamics in a transiently populated protein folding intermediate}}, doi = {10.1021/ja302598j}, volume = {134}, year = {2012}, } @article{8467, abstract = {Partial deuteration is a powerful tool to increase coherence life times and spectral resolution in proton solid-state NMR. The J coupling to deuterium needs, however, to be decoupled to maintain the good resolution in the (usually indirect) 13C dimension(s). We present a simple and reversible way to expand a commercial 1.3 mm HCN MAS probe with a 2H channel with sufficient field strength for J-decoupling of deuterium, namely 2–3 kHz. The coil is placed at the outside of the stator and requires no significant modifications to the probe. The performance and the realizable gains in sensitivity and resolution are demonstrated using perdeuterated ubiquitin, with selectively CHD2-labeled methyl groups.}, author = {Huber, Matthias and With, Oliver and Schanda, Paul and Verel, René and Ernst, Matthias and Meier, Beat H.}, issn = {1090-7807}, journal = {Journal of Magnetic Resonance}, pages = {76--80}, publisher = {Elsevier}, title = {{A supplementary coil for 2H decoupling with commercial HCN MAS probes}}, doi = {10.1016/j.jmr.2011.10.010}, volume = {214}, year = {2012}, } @article{8502, abstract = {The famous ergodic hypothesis suggests that for a typical Hamiltonian on a typical energy surface nearly all trajectories are dense. KAM theory disproves it. Ehrenfest (The Conceptual Foundations of the Statistical Approach in Mechanics. Ithaca, NY: Cornell University Press, 1959) and Birkhoff (Collected Math Papers. Vol 2, New York: Dover, pp 462–465, 1968) stated the quasi-ergodic hypothesis claiming that a typical Hamiltonian on a typical energy surface has a dense orbit. This question is wide open. Herman (Proceedings of the International Congress of Mathematicians, Vol II (Berlin, 1998). Doc Math 1998, Extra Vol II, Berlin: Int Math Union, pp 797–808, 1998) proposed to look for an example of a Hamiltonian near H0(I)=⟨I,I⟩2 with a dense orbit on the unit energy surface. In this paper we construct a Hamiltonian H0(I)+εH1(θ,I,ε) which has an orbit dense in a set of maximal Hausdorff dimension equal to 5 on the unit energy surface.}, author = {Kaloshin, Vadim and Saprykina, Maria}, issn = {0010-3616}, journal = {Communications in Mathematical Physics}, keywords = {Mathematical Physics, Statistical and Nonlinear Physics}, number = {3}, pages = {643--697}, publisher = {Springer Nature}, title = {{An example of a nearly integrable Hamiltonian system with a trajectory dense in a set of maximal Hausdorff dimension}}, doi = {10.1007/s00220-012-1532-x}, volume = {315}, year = {2012}, } @article{858, abstract = {ackground: The evolution and genomic stop codon frequencies have not been rigorously studied with the exception of coding of non-canonical amino acids. Here we study the rate of evolution and frequency distribution of stop codons in bacterial genomes.Results: We show that in bacteria stop codons evolve slower than synonymous sites, suggesting the action of weak negative selection. However, the frequency of stop codons relative to genomic nucleotide content indicated that this selection regime is not straightforward. The frequency of TAA and TGA stop codons is GC-content dependent, with TAA decreasing and TGA increasing with GC-content, while TAG frequency is independent of GC-content. Applying a formal, analytical model to these data we found that the relationship between stop codon frequencies and nucleotide content cannot be explained by mutational biases or selection on nucleotide content. However, with weak nucleotide content-dependent selection on TAG, -0.5 < Nes < 1.5, the model fits all of the data and recapitulates the relationship between TAG and nucleotide content. For biologically plausible rates of mutations we show that, in bacteria, TAG stop codon is universally associated with lower fitness, with TAA being the optimal for G-content < 16% while for G-content > 16% TGA has a higher fitness than TAG.Conclusions: Our data indicate that TAG codon is universally suboptimal in the bacterial lineage, such that TAA is likely to be the preferred stop codon for low GC content while the TGA is the preferred stop codon for high GC content. The optimization of stop codon usage may therefore be useful in genome engineering or gene expression optimization applications.Reviewers: This article was reviewed by Michail Gelfand, Arcady Mushegian and Shamil Sunyaev. For the full reviews, please go to the Reviewers' Comments section.}, author = {Povolotskaya, Inna and Fyodor Kondrashov and Ledda, Alice and Vlasov, Peter K}, journal = {Biology Direct}, publisher = {BioMed Central}, title = {{Stop codons in bacteria are not selectively equivalent}}, doi = {10.1186/1745-6150-7-30}, volume = {7}, year = {2012}, } @article{900, abstract = {The main forces directing long-term molecular evolution remain obscure. A sizable fraction of amino-acid substitutions seem to be fixed by positive selection, but it is unclear to what degree long-term protein evolution is constrained by epistasis, that is, instances when substitutions that are accepted in one genotype are deleterious in another. Here we obtain a quantitative estimate of the prevalence of epistasis in long-term protein evolution by relating data on amino-acid usage in 14 organelle proteins and 2 nuclear-encoded proteins to their rates of short-term evolution. We studied multiple alignments of at least 1,000 orthologues for each of these 16 proteins from species from a diverse phylogenetic background and found that an average site contained approximately eight different amino acids. Thus, without epistasis an average site should accept two-fifths of all possible amino acids, and the average rate of amino-acid substitutions should therefore be about three-fifths lower than the rate of neutral evolution. However, we found that the measured rate of amino-acid substitution in recent evolution is 20 times lower than the rate of neutral evolution and an order of magnitude lower than that expected in the absence of epistasis. These data indicate that epistasis is pervasive throughout protein evolution: about 90 per cent of all amino-acid substitutions have a neutral or beneficial impact only in the genetic backgrounds in which they occur, and must therefore be deleterious in a different background of other species. Our findings show that most amino-acid substitutions have different fitness effects in different species and that epistasis provides the primary conceptual framework to describe the tempo and mode of long-term protein evolution.}, author = {Breen, Michael S and Kemena, Carsten and Vlasov, Peter K and Notredame, Cédric and Fyodor Kondrashov}, journal = {Nature}, number = {7421}, pages = {535 -- 538}, publisher = {Nature Publishing Group}, title = {{Epistasis as the primary factor in molecular evolution}}, doi = {10.1038/nature11510}, volume = {490}, year = {2012}, } @article{9014, abstract = {In this Letter, we explore experimentally the phase behavior of a dense active suspension of self-propelled colloids. In addition to a solidlike and gaslike phase observed for high and low densities, a novel cluster phase is reported at intermediate densities. This takes the form of a stationary assembly of dense aggregates—resulting from a permanent dynamical merging and separation of active colloids—whose average size grows with activity as a linear function of the self-propelling velocity. While different possible scenarios can be considered to account for these observations—such as a generic velocity weakening instability recently put forward—we show that the experimental results are reproduced mathematically by a chemotactic aggregation mechanism, originally introduced to account for bacterial aggregation and accounting here for diffusiophoretic chemical interaction between colloidal swimmers.}, author = {Theurkauff, I. and Cottin-Bizonne, C. and Palacci, Jérémie A and Ybert, C. and Bocquet, L.}, issn = {10797114}, journal = {Physical Review Letters}, number = {26}, publisher = {American Physical Society }, title = {{Dynamic clustering in active colloidal suspensions with chemical signaling}}, doi = {10.1103/physrevlett.108.268303}, volume = {108}, year = {2012}, } @article{91, abstract = {We demonstrate how to appropriately estimate the zero-frequency (static) hyperpolarizability of an organic molecule from its charge distribution, and we explore applications of these estimates for identifying and evaluating new organic nonlinear optical (NLO) materials. First, we calculate hyperpolarizabilities from Hartree-Fock-derived charge distributions and find order-of-magnitude agreement with experimental values. We show that these simple arithmetic calculations will enable systematic searches for new organic NLO molecules. Second, we derive hyperpolarizabilities from crystallographic data using a multipolar charge-density analysis and find good agreement with empirical calculations. This demonstrates an experimental determination of the full static hyperpolarizability tensor in a solid-state sample. }, author = {Higginbotham, Andrew P and Cole, Jacqueline and Blood Forsythe, Martin and Hickstein, Daniel}, journal = {Journal of Applied Physics}, number = {3}, publisher = {American Institute of Physics}, title = {{Identifying and evaluating organic nonlinear optical materials via molecular moments}}, doi = {10.1063/1.3678593}, volume = {111}, year = {2012}, } @article{9142, abstract = {In models of radiative–convective equilibrium it is known that convection can spontaneously aggregate into one single localized moist region if the domain is large enough. The large changes in the mean climate state and radiative fluxes accompanying this self-aggregation raise questions as to what simulations at lower resolutions with parameterized convection, in similar homogeneous geometries, should be expected to produce to be considered successful in mimicking a cloud-resolving model. The authors investigate this self-aggregation in a nonrotating, three-dimensional cloud-resolving model on a square domain without large-scale forcing. It is found that self-aggregation is sensitive not only to the domain size, but also to the horizontal resolution. With horizontally homogeneous initial conditions, convective aggregation only occurs on domains larger than about 200km and with resolutions coarser than about 2km in the model examined. The system exhibits hysteresis, so that with aggregated initial conditions, convection remains aggregated even at our finest resolution, 500m, as long as the domain is greater than 200–300km. The sensitivity of self-aggregation to resolution and domain size in this model is due to the sensitivity of the distribution of low clouds to these two parameters. Indeed, the mechanism responsible for the aggregation of convection is the dynamical response to the longwave radiative cooling from low clouds. Strong longwave cooling near cloud top in dry regions forces downward motion, which by continuity generates inflow near cloud top and near-surface outflow from dry regions. This circulation results in the net export of moist static energy from regions with low moist static energy, yielding a positive feedback.}, author = {Muller, Caroline J and Held, Isaac M.}, issn = {0022-4928}, journal = {Journal of the Atmospheric Sciences}, keywords = {Atmospheric Science}, number = {8}, pages = {2551--2565}, publisher = {American Meteorological Society}, title = {{Detailed investigation of the self-aggregation of convection in cloud-resolving simulations}}, doi = {10.1175/jas-d-11-0257.1}, volume = {69}, year = {2012}, } @article{9451, abstract = {The Arabidopsis thaliana central cell, the companion cell of the egg, undergoes DNA demethylation before fertilization, but the targeting preferences, mechanism, and biological significance of this process remain unclear. Here, we show that active DNA demethylation mediated by the DEMETER DNA glycosylase accounts for all of the demethylation in the central cell and preferentially targets small, AT-rich, and nucleosome-depleted euchromatic transposable elements. The vegetative cell, the companion cell of sperm, also undergoes DEMETER-dependent demethylation of similar sequences, and lack of DEMETER in vegetative cells causes reduced small RNA–directed DNA methylation of transposons in sperm. Our results demonstrate that demethylation in companion cells reinforces transposon methylation in plant gametes and likely contributes to stable silencing of transposable elements across generations.}, author = {Ibarra, Christian A. and Feng, Xiaoqi and Schoft, Vera K. and Hsieh, Tzung-Fu and Uzawa, Rie and Rodrigues, Jessica A. and Zemach, Assaf and Chumak, Nina and Machlicova, Adriana and Nishimura, Toshiro and Rojas, Denisse and Fischer, Robert L. and Tamaru, Hisashi and Zilberman, Daniel}, issn = {1095-9203}, journal = {Science}, number = {6100}, pages = {1360--1364}, publisher = {American Association for the Advancement of Science}, title = {{Active DNA demethylation in plant companion cells reinforces transposon methylation in gametes}}, doi = {10.1126/science.1224839}, volume = {337}, year = {2012}, } @article{9535, abstract = {The most well-studied function of DNA methylation in eukaryotic cells is the transcriptional silencing of genes and transposons. More recent results showed that many eukaryotes methylate the bodies of genes as well and that this methylation correlates with transcriptional activity rather than repression. The purpose of gene body methylation remains mysterious, but is potentially related to the histone variant H2A.Z. Studies in plants and animals have shown that the genome-wide distributions of H2A.Z and DNA methylation are strikingly anticorrelated. Furthermore, we and other investigators have shown that this relationship is likely to be the result of an ancient but unknown mechanism by which DNA methylation prevents the incorporation of H2A.Z. Recently, we discovered strong correlations between the presence of H2A.Z within gene bodies, the degree to which a gene's expression varies across tissue types or environmental conditions, and transcriptional misregulation in an h2a.z mutant. We propose that one basal function of gene body methylation is the establishment of constitutive expression patterns within housekeeping genes by excluding H2A.Z from their bodies.}, author = {Coleman-Derr, D. and Zilberman, Daniel}, issn = {1943-4456}, journal = {Cold Spring Harbor Symposia on Quantitative Biology}, pages = {147--154}, publisher = {Cold Spring Harbor Laboratory Press}, title = {{DNA methylation, H2A.Z, and the regulation of constitutive expression}}, doi = {10.1101/sqb.2012.77.014944}, volume = {77}, year = {2012}, }