@article{1331, abstract = {Cytokinin is a phytohormone that is well known for its roles in numerous plant growth and developmental processes, yet it has also been linked to abiotic stress response in a less defined manner. Arabidopsis (Arabidopsis thaliana) Cytokinin Response Factor 6 (CRF6) is a cytokinin-responsive AP2/ERF-family transcription factor that, through the cytokinin signaling pathway, plays a key role in the inhibition of dark-induced senescence. CRF6 expression is also induced by oxidative stress, and here we show a novel function for CRF6 in relation to oxidative stress and identify downstream transcriptional targets of CRF6 that are repressed in response to oxidative stress. Analysis of transcriptomic changes in wild-type and crf6 mutant plants treated with H2O2 identified CRF6-dependent differentially expressed transcripts, many of which were repressed rather than induced. Moreover, many repressed genes also show decreased expression in 35S:CRF6 overexpressing plants. Together, these findings suggest that CRF6 functions largely as a transcriptional repressor. Interestingly, among the H2O2 repressed CRF6-dependent transcripts was a set of five genes associated with cytokinin processes: (signaling) ARR6, ARR9, ARR11, (biosynthesis) LOG7, and (transport) ABCG14. We have examined mutants of these cytokinin-associated target genes to reveal novel connections to oxidative stress. Further examination of CRF6-DNA interactions indicated that CRF6 may regulate its targets both directly and indirectly. Together, this shows that CRF6 functions during oxidative stress as a negative regulator to control this cytokinin-associated module of CRF6- dependent genes and establishes a novel connection between cytokinin and oxidative stress response.}, author = {Zwack, Paul and De Clercq, Inge and Howton, Timothy and Hallmark, H Tucker and Hurny, Andrej and Keshishian, Erika and Parish, Alyssa and Benková, Eva and Mukhtar, M Shahid and Van Breusegem, Frank and Rashotte, Aaron}, issn = {1532-2548}, journal = {Plant Physiology}, number = {2}, pages = {1249 -- 1258}, publisher = {American Society of Plant Biologists}, title = {{Cytokinin response factor 6 represses cytokinin-associated genes during oxidative stress}}, doi = {10.1104/pp.16.00415}, volume = {172}, year = {2016}, } @article{1332, abstract = {Antibiotic-sensitive and -resistant bacteria coexist in natural environments with low, if detectable, antibiotic concentrations. Except possibly around localized antibiotic sources, where resistance can provide a strong advantage, bacterial fitness is dominated by stresses unaffected by resistance to the antibiotic. How do such mixed and heterogeneous conditions influence the selective advantage or disadvantage of antibiotic resistance? Here we find that sub-inhibitory levels of tetracyclines potentiate selection for or against tetracycline resistance around localized sources of almost any toxin or stress. Furthermore, certain stresses generate alternating rings of selection for and against resistance around a localized source of the antibiotic. In these conditions, localized antibiotic sources, even at high strengths, can actually produce a net selection against resistance to the antibiotic. Our results show that interactions between the effects of an antibiotic and other stresses in inhomogeneous environments can generate pervasive, complex patterns of selection both for and against antibiotic resistance.}, author = {Chait, Remy P and Palmer, Adam and Yelin, Idan and Kishony, Roy}, journal = {Nature Communications}, publisher = {Nature Publishing Group}, title = {{Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments}}, doi = {10.1038/ncomms10333}, volume = {7}, year = {2016}, } @article{1333, abstract = {Social dilemmas force players to balance between personal and collective gain. In many dilemmas, such as elected governments negotiating climate-change mitigation measures, the decisions are made not by individual players but by their representatives. However, the behaviour of representatives in social dilemmas has not been investigated experimentally. Here inspired by the negotiations for greenhouse-gas emissions reductions, we experimentally study a collective-risk social dilemma that involves representatives deciding on behalf of their fellow group members. Representatives can be re-elected or voted out after each consecutive collective-risk game. Selfish players are preferentially elected and are hence found most frequently in the "representatives" treatment. Across all treatments, we identify the selfish players as extortioners. As predicted by our mathematical model, their steadfast strategies enforce cooperation from fair players who finally compensate almost completely the deficit caused by the extortionate co-players. Everybody gains, but the extortionate representatives and their groups gain the most.}, author = {Milinski, Manfred and Hilbe, Christian and Semmann, Dirk and Sommerfeld, Ralf and Marotzke, Jochem}, journal = {Nature Communications}, publisher = {Nature Publishing Group}, title = {{Humans choose representatives who enforce cooperation in social dilemmas through extortion}}, doi = {10.1038/ncomms10915}, volume = {7}, year = {2016}, } @article{1334, abstract = {Hippocampal neurons encode a cognitive map of space. These maps are thought to be updated during learning and in response to changes in the environment through activity-dependent synaptic plasticity. Here we examine how changes in activity influence spatial coding in rats using halorhodopsin-mediated, spatially selective optogenetic silencing. Halorhoposin stimulation leads to light-induced suppression in many place cells and interneurons; some place cells increase their firing through disinhibition, whereas some show no effect. We find that place fields of the unaffected subpopulation remain stable. On the other hand, place fields of suppressed place cells were unstable, showing remapping across sessions before and after optogenetic inhibition. Disinhibited place cells had stable maps but sustained an elevated firing rate. These findings suggest that place representation in the hippocampus is constantly governed by activity-dependent processes, and that disinhibition may provide a mechanism for rate remapping.}, author = {Schönenberger, Philipp and O'Neill, Joseph and Csicsvari, Jozsef L}, journal = {Nature Communications}, publisher = {Nature Publishing Group}, title = {{Activity dependent plasticity of hippocampal place maps}}, doi = {10.1038/ncomms11824}, volume = {7}, year = {2016}, } @inproceedings{1335, abstract = {In this paper we review various automata-theoretic formalisms for expressing quantitative properties. We start with finite-state Boolean automata that express the traditional regular properties. We then consider weighted ω-automata that can measure the average density of events, which finite-state Boolean automata cannot. However, even weighted ω-automata cannot express basic performance properties like average response time. We finally consider two formalisms of weighted ω-automata with monitors, where the monitors are either (a) counters or (b) weighted automata themselves. We present a translation result to establish that these two formalisms are equivalent. Weighted ω-automata with monitors generalize weighted ω-automata, and can express average response time property. They present a natural, robust, and expressive framework for quantitative specifications, with important decidable properties.}, author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Otop, Jan}, location = {Edinburgh, United Kingdom}, pages = {23 -- 38}, publisher = {Springer}, title = {{Quantitative monitor automata}}, doi = {10.1007/978-3-662-53413-7_2}, volume = {9837}, year = {2016}, } @article{8241, abstract = {Background: Anticancer vaccines could represent a valuable complementary strategy to established therapies, especially in settings of early stage and minimal residual disease. HER-2 is an important target for immunotherapy and addressed by the monoclonal antibody trastuzumab. We have previously generated HER-2 mimotope peptides from phage display libraries. The synthesized peptides were coupled to carriers and applied for epitope-specific induction of trastuzumab-like IgG. For simplification and to avoid methodological limitations of synthesis and coupling chemistry, we herewith present a novel and optimized approach by using adeno-associated viruses (AAV) as effective and high-density mimotope-display system, which can be directly used for vaccination. Methods: An AAV capsid display library was constructed by genetically incorporating random peptides in a plasmid encoding the wild-type AAV2 capsid protein. AAV clones, expressing peptides specifically reactive to trastuzumab, were employed to immunize BALB/c mice. Antibody titers against human HER-2 were determined, and the isotype composition and functional properties of these were tested. Finally, prophylactically immunized mice were challenged with human HER-2 transfected mouse D2F2/E2 cells. Results: HER-2 mimotope AAV-vaccines induced antibodies specific to human HER-2. Two clones were selected for immunization of mice, which were subsequently grafted D2F2/E2 cells. Both mimotope AAV clones delayed the growth of tumors significantly, as compared to controls. Conclusion: In this study, a novel mimotope AAV-based platform was created allowing the isolation of mimotopes, which can be directly used as anticancer vaccines. The example of trastuzumab AAV-mimotopes demonstrates that this vaccine strategy could help to establish active immunotherapy for breast-cancer patients.}, author = {Singer, Josef and Manzano-Szalai, Krisztina and Fazekas, Judit and Thell, Kathrin and Bentley-Lukschal, Anna and Stremnitzer, Caroline and Roth-Walter, Franziska and Weghofer, Margit and Ritter, Mirko and Pino Tossi, Kerstin and Hörer, Markus and Michaelis, Uwe and Jensen-Jarolim, Erika}, issn = {2162-402X}, journal = {OncoImmunology}, number = {7}, publisher = {Taylor & Francis}, title = {{Proof of concept study with an HER-2 mimotope anticancer vaccine deduced from a novel AAV-mimotope library platform}}, doi = {10.1080/2162402x.2016.1171446}, volume = {5}, year = {2016}, } @inproceedings{8300, abstract = {The integration of social networking concepts into Internet of Things systems is a burgeoning topic of research that promises to support novel and more powerful applications. In this paper we focus on the design and implementation of a highly scalable Trust and Reputation Model for the Internet of Things based on the social approach that the COSMOS project introduces, as part of its final results. We create our model by combining popular solutions proposed for Peer-to-Peer and mobile ad-hoc networks and adapting them on the Internet of Things concept. Each Thing can compute the Trust index of another Thing based on its own experiences, while it has the capability of determining its Reputation Index either by consulting its other “friends” (Followees) or referring to the Platform, a management system used in COSMOS. The model is tested through simulations of the proposed social system, demonstrating the ability of TRM-SIoT to achieve the Social Exclusion of malicious nodes and collectives from the network, with low computational overhead and high scalability. Furthermore, due to the adaptive nature of the system, Social Reintegration of these nodes is also possible.}, author = {Kokoris Kogias, Eleftherios and Voutyras, Orfefs and Varvarigou, Theodora}, booktitle = {2016 IEEE 21st International Conference on Emerging Technologies and Factory Automation}, isbn = {9781509013142}, location = {Berlin, Germany}, publisher = {IEEE}, title = {{TRM-SIoT: A scalable hybrid trust & reputation model for the social Internet of Things}}, doi = {10.1109/etfa.2016.7733612}, year = {2016}, } @inproceedings{8302, abstract = {While showing great promise, Bitcoin requires users to wait tens of minutes for transactions to commit, and even then, offering only probabilistic guarantees. This paper introduces ByzCoin, a novel Byzantine consensus protocol that leverages scalable collective signing to commit Bitcoin transactions irreversibly within seconds. ByzCoin achieves Byzantine consensus while preserving Bitcoin’s open membership by dynamically forming hash power-proportionate consensus groups that represent recently-successful block miners. ByzCoin employs communication trees to optimize transaction commitment and verification under normal operation while guaranteeing safety and liveness under Byzantine faults, up to a near-optimal tolerance of f faulty group members among 3f + 2 total. ByzCoin mitigates double spending and selfish mining attacks by producing collectively signed transaction blocks within one minute of transaction submission. Tree-structured communication further reduces this latency to less than 30 seconds. Due to these optimizations, ByzCoin achieves a throughput higher than Paypal currently handles, with a confirmation latency of 15-20 seconds.}, author = {Kokoris Kogias, Eleftherios and Jovanovic, Philipp and Gailly, Nicolas and Khoffi, Ismail and Gasser, Linus and Ford, Bryan}, booktitle = {Proceedings of the 25th USENIX Conference on Security Symposium}, isbn = {9781931971324}, location = {Austin, TX, United States}, pages = {279–296}, publisher = {USENIX Association}, title = {{Enhancing bitcoin security and performance with strong consistency via collective signing}}, year = {2016}, } @article{8452, abstract = {During spore formation in Bacillus subtilis a transenvelope complex is assembled across the double membrane that separates the mother cell and forespore. This complex (called the “A–Q complex”) is required to maintain forespore development and is composed of proteins with remote homology to components of type II, III, and IV secretion systems found in Gram-negative bacteria. Here, we show that one of these proteins, SpoIIIAG, which has remote homology to ring-forming proteins found in type III secretion systems, assembles into an oligomeric ring in the periplasmic-like space between the two membranes. Three-dimensional reconstruction of images generated by cryo-electron microscopy indicates that the SpoIIIAG ring has a cup-and-saucer architecture with a 6-nm central pore. Structural modeling of SpoIIIAG generated a 24-member ring with dimensions similar to those of the EM-derived saucer. Point mutations in the predicted oligomeric interface disrupted ring formation in vitro and impaired forespore gene expression and efficient spore formation in vivo. Taken together, our data provide strong support for the model in which the A–Q transenvelope complex contains a conduit that connects the mother cell and forespore. We propose that a set of stacked rings spans the intermembrane space, as has been found for type III secretion systems.}, author = {Rodrigues, Christopher D. A. and Henry, Xavier and Neumann, Emmanuelle and Kurauskas, Vilius and Bellard, Laure and Fichou, Yann and Schanda, Paul and Schoehn, Guy and Rudner, David Z. and Morlot, Cecile}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences}, number = {41}, pages = {11585--11590}, publisher = {National Academy of Sciences}, title = {{A ring-shaped conduit connects the mother cell and forespore during sporulation in Bacillus subtilis}}, doi = {10.1073/pnas.1609604113}, volume = {113}, year = {2016}, } @article{8453, abstract = {Transverse relaxation rate measurements in magic-angle spinning solid-state nuclear magnetic resonance provide information about molecular motions occurring on nanosecond-to-millisecond (ns–ms) time scales. The measurement of heteronuclear (13C, 15N) relaxation rate constants in the presence of a spin-lock radiofrequency field (R1ρ relaxation) provides access to such motions, and an increasing number of studies involving R1ρ relaxation in proteins have been reported. However, two factors that influence the observed relaxation rate constants have so far been neglected, namely, (1) the role of CSA/dipolar cross-correlated relaxation (CCR) and (2) the impact of fast proton spin flips (i.e., proton spin diffusion and relaxation). We show that CSA/D CCR in R1ρ experiments is measurable and that the CCR rate constant depends on ns–ms motions; it can thus provide insight into dynamics. We find that proton spin diffusion attenuates this CCR due to its decoupling effect on the doublet components. For measurements of dynamics, the use of R1ρ rate constants has practical advantages over the use of CCR rates, and this article reveals factors that have so far been disregarded and which are important for accurate measurements and interpretation.}, author = {Kurauskas, Vilius and Weber, Emmanuelle and Hessel, Audrey and Ayala, Isabel and Marion, Dominique and Schanda, Paul}, issn = {1520-6106}, journal = {The Journal of Physical Chemistry B}, keywords = {Physical and Theoretical Chemistry, Materials Chemistry, Surfaces, Coatings and Films}, number = {34}, pages = {8905--8913}, publisher = {American Chemical Society}, title = {{Cross-correlated relaxation of dipolar coupling and chemical-shift anisotropy in magic-angle spinning R1ρ NMR measurements: Application to protein backbone dynamics measurements}}, doi = {10.1021/acs.jpcb.6b06129}, volume = {120}, year = {2016}, } @article{8454, abstract = {Magic-angle spinning solid-state NMR spectroscopy is an important technique to study molecular structure, dynamics and interactions, and is rapidly gaining importance in biomolecular sciences. Here we provide an overview of experimental approaches to study molecular dynamics by MAS solid-state NMR, with an emphasis on the underlying theoretical concepts and differences of MAS solid-state NMR compared to solution-state NMR. The theoretical foundations of nuclear spin relaxation are revisited, focusing on the particularities of spin relaxation in solid samples under magic-angle spinning. We discuss the range of validity of Redfield theory, as well as the inherent multi-exponential behavior of relaxation in solids. Experimental challenges for measuring relaxation parameters in MAS solid-state NMR and a few recently proposed relaxation approaches are discussed, which provide information about time scales and amplitudes of motions ranging from picoseconds to milliseconds. We also discuss the theoretical basis and experimental measurements of anisotropic interactions (chemical-shift anisotropies, dipolar and quadrupolar couplings), which give direct information about the amplitude of motions. The potential of combining relaxation data with such measurements of dynamically-averaged anisotropic interactions is discussed. Although the focus of this review is on the theoretical foundations of dynamics studies rather than their application, we close by discussing a small number of recent dynamics studies, where the dynamic properties of proteins in crystals are compared to those in solution.}, author = {Schanda, Paul and Ernst, Matthias}, issn = {0079-6565}, journal = {Progress in Nuclear Magnetic Resonance Spectroscopy}, number = {8}, pages = {1--46}, publisher = {Elsevier}, title = {{Studying dynamics by magic-angle spinning solid-state NMR spectroscopy: Principles and applications to biomolecules}}, doi = {10.1016/j.pnmrs.2016.02.001}, volume = {96}, year = {2016}, } @article{8455, abstract = {Solid-state NMR spectroscopy allows the characterization of the structure, interactions and dynamics of insoluble and/or very large proteins. Sensitivity and resolution are often major challenges for obtaining atomic-resolution information, in particular for very large protein complexes. Here we show that the use of deuterated, specifically CH3-labelled proteins result in significant sensitivity gains compared to previously employed CHD2 labelling, while line widths increase only marginally. We apply this labelling strategy to a 468 kDa-large dodecameric aminopeptidase, TET2, and the 1.6 MDa-large 50S ribosome subunit of Thermus thermophilus.}, author = {Kurauskas, Vilius and Crublet, Elodie and Macek, Pavel and Kerfah, Rime and Gauto, Diego F. and Boisbouvier, Jérôme and Schanda, Paul}, issn = {1359-7345}, journal = {Chemical Communications}, keywords = {Materials Chemistry, Electronic, Optical and Magnetic Materials, General Chemistry, Surfaces, Coatings and Films, Metals and Alloys, Ceramics and Composites, Catalysis}, number = {61}, pages = {9558--9561}, publisher = {Royal Society of Chemistry}, title = {{Sensitive proton-detected solid-state NMR spectroscopy of large proteins with selective CH3labelling: Application to the 50S ribosome subunit}}, doi = {10.1039/c6cc04484k}, volume = {52}, year = {2016}, } @article{849, abstract = {Understanding the principles that led to the current complexity of the genetic code is a central question in evolution. Expansion of the genetic code required the selection of new transfer RNAs (tRNAs) with specific recognition signals that allowed them to be matured, modified, aminoacylated, and processed by the ribosome without compromising the fidelity or efficiency of protein synthesis. We show that saturation of recognition signals blocks the emergence of new tRNA identities and that the rate of nucleotide substitutions in tRNAs is higher in species with fewer tRNA genes. We propose that the growth of the genetic code stalled because a limit was reached in the number of identity elements that can be effectively used in the tRNA structure.}, author = {Saint-Léger, Adélaïde and Bello, Carla and Dans, Pablo D and Torres, Adrian G and Novoa, Eva M and Camacho, Noelia and Orozco, Modesto and Fyodor Kondrashov and Ribas De Pouplana, Lluís}, journal = {Science advances}, number = {4}, pages = {e1501860 -- e1501860}, publisher = {American Association for the Advancement of Science}, title = {{Saturation of recognition elements blocks evolution of new tRNA identities}}, doi = {10.1126/sciadv.1501860}, volume = {2}, year = {2016}, } @article{8493, abstract = {In this paper we study a so-called separatrix map introduced by Zaslavskii–Filonenko (Sov Phys JETP 27:851–857, 1968) and studied by Treschev (Physica D 116(1–2):21–43, 1998; J Nonlinear Sci 12(1):27–58, 2002), Piftankin (Nonlinearity (19):2617–2644, 2006) Piftankin and Treshchëv (Uspekhi Mat Nauk 62(2(374)):3–108, 2007). We derive a second order expansion of this map for trigonometric perturbations. In Castejon et al. (Random iteration of maps of a cylinder and diffusive behavior. Preprint available at arXiv:1501.03319, 2015), Guardia and Kaloshin (Stochastic diffusive behavior through big gaps in a priori unstable systems (in preparation), 2015), and Kaloshin et al. (Normally Hyperbolic Invariant Laminations and diffusive behavior for the generalized Arnold example away from resonances. Preprint available at http://www.terpconnect.umd.edu/vkaloshi/, 2015), applying the results of the present paper, we describe a class of nearly integrable deterministic systems with stochastic diffusive behavior.}, author = {Guardia, M. and Kaloshin, Vadim and Zhang, J.}, issn = {0010-3616}, journal = {Communications in Mathematical Physics}, pages = {321--361}, publisher = {Springer Nature}, title = {{A second order expansion of the separatrix map for trigonometric perturbations of a priori unstable systems}}, doi = {10.1007/s00220-016-2705-9}, volume = {348}, year = {2016}, } @article{8494, abstract = {We prove a form of Arnold diffusion in the a-priori stable case. Let H0(p)+ϵH1(θ,p,t),θ∈Tn,p∈Bn,t∈T=R/T, be a nearly integrable system of arbitrary degrees of freedom n⩾2 with a strictly convex H0. We show that for a “generic” ϵH1, there exists an orbit (θ,p) satisfying ∥p(t)−p(0)∥>l(H1)>0, where l(H1) is independent of ϵ. The diffusion orbit travels along a codimension-1 resonance, and the only obstruction to our construction is a finite set of additional resonances. For the proof we use a combination of geometric and variational methods, and manage to adapt tools which have recently been developed in the a-priori unstable case.}, author = {Bernard, Patrick and Kaloshin, Vadim and Zhang, Ke}, issn = {0001-5962}, journal = {Acta Mathematica}, number = {1}, pages = {1--79}, publisher = {Institut Mittag-Leffler}, title = {{Arnold diffusion in arbitrary degrees of freedom and normally hyperbolic invariant cylinders}}, doi = {10.1007/s11511-016-0141-5}, volume = {217}, year = {2016}, } @article{8496, author = {Avila, Artur and De Simoi, Jacopo and Kaloshin, Vadim}, issn = {0003-486X}, journal = {Annals of Mathematics}, number = {2}, pages = {527--558}, publisher = {Princeton University Press}, title = {{An integrable deformation of an ellipse of small eccentricity is an ellipse}}, doi = {10.4007/annals.2016.184.2.5}, volume = {184}, year = {2016}, } @article{8497, abstract = {We study the dynamics of the restricted planar three-body problem near mean motion resonances, i.e. a resonance involving the Keplerian periods of the two lighter bodies revolving around the most massive one. This problem is often used to model Sun–Jupiter–asteroid systems. For the primaries (Sun and Jupiter), we pick a realistic mass ratio μ=10−3 and a small eccentricity e0>0. The main result is a construction of a variety of non local diffusing orbits which show a drastic change of the osculating (instant) eccentricity of the asteroid, while the osculating semi major axis is kept almost constant. The proof relies on the careful analysis of the circular problem, which has a hyperbolic structure, but for which diffusion is prevented by KAM tori. In the proof we verify certain non-degeneracy conditions numerically. Based on the work of Treschev, it is natural to conjecture that the time of diffusion for this problem is ∼−ln(μe0)μ3/2e0. We expect our instability mechanism to apply to realistic values of e0 and we give heuristic arguments in its favor. If so, the applicability of Nekhoroshev theory to the three-body problem as well as the long time stability become questionable. It is well known that, in the Asteroid Belt, located between the orbits of Mars and Jupiter, the distribution of asteroids has the so-called Kirkwood gaps exactly at mean motion resonances of low order. Our mechanism gives a possible explanation of their existence. To relate the existence of Kirkwood gaps with Arnol'd diffusion, we also state a conjecture on its existence for a typical ϵ-perturbation of the product of the pendulum and the rotator. Namely, we predict that a positive conditional measure of initial conditions concentrated in the main resonance exhibits Arnol’d diffusion on time scales −lnϵϵ2.}, author = {Féjoz, Jacques and Guàrdia, Marcel and Kaloshin, Vadim and Roldán, Pablo}, issn = {1435-9855}, journal = {Journal of the European Mathematical Society}, number = {10}, pages = {2315--2403}, publisher = {European Mathematical Society Publishing House}, title = {{Kirkwood gaps and diffusion along mean motion resonances in the restricted planar three-body problem}}, doi = {10.4171/jems/642}, volume = {18}, year = {2016}, } @article{850, abstract = {Fitness landscapes depict how genotypes manifest at the phenotypic level and form the basis of our understanding of many areas of biology, yet their properties remain elusive. Previous studies have analysed specific genes, often using their function as a proxy for fitness, experimentally assessing the effect on function of single mutations and their combinations in a specific sequence or in different sequences. However, systematic high-throughput studies of the local fitness landscape of an entire protein have not yet been reported. Here we visualize an extensive region of the local fitness landscape of the green fluorescent protein from Aequorea Victoria (avGFP) by measuring the native function (fluorescence) of tens of thousands of derivative genotypes of avGFP. We show that the fitness landscape of avGFP is narrow, with 3/4 of the derivatives with a single mutation showing reduced fluorescence and half of the derivatives with four mutations being completely non-fluorescent. The narrowness is enhanced by epistasis, which was detected in up to 30% of genotypes with multiple mutations and mostly occurred through the cumulative effect of slightly deleterious mutations causing a threshold-like decrease in protein stability and a concomitant loss of fluorescence. A model of orthologous sequence divergence spanning hundreds of millions of years predicted the extent of epistasis in our data, indicating congruence between the fitness landscape properties at the local and global scales. The characterization of the local fitness landscape of avGFP has important implications for several fields including molecular evolution, population genetics and protein design.}, author = {Karen Sarkisyan and Bolotin, Dmitry A and Meer, Margarita V and Usmanova, Dinara R and Mishin, Alexander S and Sharonov, George V and Ivankov, Dmitry N and Bozhanova, Nina G and Baranov, Mikhail S and Soylemez, Onuralp and Bogatyreva, Natalya S and Vlasov, Peter K and Egorov, Evgeny S and Logacheva, Maria D and Kondrashov, Alexey S and Chudakov, Dmitriy M and Putintseva, Ekaterina V and Mamedov, Ilgar Z and Tawfik, Dan S and Lukyanov, Konstantin A and Fyodor Kondrashov}, journal = {Nature}, pages = {397 -- 401}, publisher = {Nature Publishing Group}, title = {{Local fitness landscape of the green fluorescent protein}}, doi = {10.1038/nature17995}, volume = {533}, year = {2016}, } @article{853, abstract = {A comparative analysis of the metagenomes from two 30 000-year-old permafrost samples, one of lake-alluvial origin and the other from late Pleistocene Ice Complex sediments, revealed significant differences within microbial communities. The late Pleistocene Ice Complex sediments (which have been characterized by the absence of methane with lower values of redox potential and Fe2+ content) showed a low abundance of methanogenic archaea and enzymes from both the carbon and nitrogen cycles, but a higher abundance of enzymes associated with the sulfur cycle. The metagenomic and geochemical analyses described in the paper provide evidence that the formation of the sampled late Pleistocene Ice Complex sediments likely took place under much more aerobic conditions than lake-alluvial sediments.}, author = {Rivkina, Elizaveta and Petrovskaya, Lada E and Vishnivetskaya, Tatiana A and Krivushin, Kirill V and Shmakova, Lyubov A and Tutukina, Maria and Meyers, Arthur J and Fyodor Kondrashov}, journal = {Biogeosciences}, number = {7}, pages = {2207 -- 2219}, publisher = {European Geosciences Union}, title = {{Metagenomic analyses of the late Pleistocene permafrost - Additional tools for reconstruction of environmental conditions}}, doi = {10.5194/bg-13-2207-2016}, volume = {13}, year = {2016}, } @article{896, abstract = {Multicellular eukaryotes have evolved a range of mechanisms for immune recognition. A widespread family involved in innate immunity are the NACHT-domain and leucine-rich-repeat-containing (NLR) proteins.Mammals have small numbers of NLR proteins, whereas in some species, mostly those without adaptive immune systems, NLRs have expanded into very large families.We describe a family of nearly 400NLR proteins encoded in the zebrafish genome. The proteins share a defining overall structure, which arose in fishes after a fusion of the core NLR domains with a B30.2 domain, but can be subdivided into four groups based on their NACHT domains. Gene conversion acting differentially on the NACHT and B30.2 domains has shaped the family and created the groups. Evidence of positive selection in the B30.2 domain indicates that this domain rather than the leucine-rich repeats acts as the pathogen recognition module. In an unusual chromosomal organization, the majority of the genes are located on one chromosome arm, interspersed with other large multigene families, including a new family encoding zinc-finger proteins. The NLR-B30.2 proteins represent a new family with diversity in the specific recognition module that is present in fishes in spite of the parallel existence of an adaptive immune system.}, author = {Howe, Kerstin L and Schiffer, Philipp H and Zielinski, Julia G and Wiehe, Thomas H and Laird, Gavin K and Marioni, John C and Soylemez, Onuralp and Fyodor Kondrashov and Leptin, Maria}, journal = {Open Biology}, number = {4}, publisher = {Royal Society, The}, title = {{Structure and evolutionary history of a large family of NLR proteins in the zebrafish}}, doi = {10.1098/rsob.160009}, volume = {6}, year = {2016}, }