@article{532, abstract = {Ethylene is a gaseous phytohormone that plays vital roles in plant growth and development. Previous studies uncovered EIN2 as an essential signal transducer linking ethylene perception on ER to transcriptional regulation in the nucleus through a “cleave and shuttle” model. In this study, we report another mechanism of EIN2-mediated ethylene signaling, whereby EIN2 imposes the translational repression of EBF1 and EBF2 mRNA. We find that the EBF1/2 3′ UTRs mediate EIN2-directed translational repression and identify multiple poly-uridylates (PolyU) motifs as functional cis elements of 3′ UTRs. Furthermore, we demonstrate that ethylene induces EIN2 to associate with 3′ UTRs and target EBF1/2 mRNA to cytoplasmic processing-body (P-body) through interacting with multiple P-body factors, including EIN5 and PABs. Our study illustrates translational regulation as a key step in ethylene signaling and presents mRNA 3′ UTR functioning as a “signal transducer” to sense and relay cellular signaling in plants.}, author = {Li, Wenyang and Ma, Mengdi and Feng, Ying and Li, Hongjiang and Wang, Yichuan and Ma, Yutong and Li, Mingzhe and An, Fengying and Guo, Hongwei}, journal = {Cell}, number = {3}, pages = {670 -- 683}, publisher = {Cell Press}, title = {{EIN2-directed translational regulation of ethylene signaling in arabidopsis}}, doi = {10.1016/j.cell.2015.09.037}, volume = {163}, year = {2015}, } @article{12632, abstract = {We investigate the performance of five glacier melt models over a multi-decadal period in order to assess their ability to model future glacier response. The models range from a simple degree-day model, based solely on air temperature, to more-sophisticated models, including the full shortwave radiation balance. In addition to the empirical models, the performance of a physically based energy-balance (EB) model is examined. The melt models are coupled to an accumulation and a surface evolution model and applied in a distributed manner to Rhonegletscher, Switzerland, over the period 1929–2012 at hourly resolution. For calibration, seasonal mass-balance measurements (2006–12) are used. Decadal ice volume changes for six periods in the years 1929–2012 serve for model validation. Over the period 2006–12, there are almost no differences in performance between the models, except for EB, which is less consistent with observations, likely due to lack of meteorological in situ data. However, simulations over the long term (1929–2012) reveal that models which include a separate term for shortwave radiation agree best with the observed ice volume changes, indicating that their melt relationships are robust in time and thus suitable for long-term modelling, in contrast to more empirical approaches that are oversensitive to temperature fluctuations.}, author = {Gabbi, Jeannette and Carenzo, Marco and Pellicciotti, Francesca and Bauder, Andreas and Funk, Martin}, issn = {1727-5652}, journal = {Journal of Glaciology}, keywords = {Earth-Surface Processes}, number = {224}, pages = {1140--1154}, publisher = {International Glaciological Society}, title = {{A comparison of empirical and physically based glacier surface melt models for long-term simulations of glacier response}}, doi = {10.3189/2014jog14j011}, volume = {60}, year = {2014}, } @article{12634, abstract = {Glaciers in the Andes of Chile seem to be shrinking and possibly loosing mass, but the number and types of studies conducted, constrained mainly by data availability, are not sufficient to provide a synopsis of glacier changes for the past or future or explain in an explicit way causes of the observed changes. In this paper, we provide a systematic review of changes in glaciers for the entire country, followed by a discussion of the studies that have provided evidence of such changes. We identify a missing type of work in distributed, physically-oriented modelling studies that are needed to bridge the gap between the numerous remote sensing studies and the specific, point scale works focused on process understanding. We use an advanced mass balance model applied to one of the best monitored glaciers in the region to investigate four main research issues that should be addressed in modelling studies for a sound assessment of glacier changes: 1) the use of physically-based models of glacier ablation (energy balance models) versus more empirical models (enhanced temperature index approaches); 2) the importance of the correct extrapolation of air temperature forcing on glaciers and in high elevation areas and the large uncertainty in model outputs associated with it; 3) the role played by snow gravitational redistribution; and 4) the uncertainty associated with future climate scenarios. We quantify differences in model outputs associated with each of these choices, and conclude with suggestions for future work directions.}, author = {Pellicciotti, Francesca and Ragettli, S. and Carenzo, M. and McPhee, J.}, issn = {0048-9697}, journal = {Science of The Total Environment}, keywords = {Pollution, Waste Management and Disposal, Environmental Chemistry, Environmental Engineering}, pages = {1197--1210}, publisher = {Elsevier}, title = {{Changes of glaciers in the Andes of Chile and priorities for future work}}, doi = {10.1016/j.scitotenv.2013.10.055}, volume = {493}, year = {2014}, } @article{12635, abstract = {Switzerland is one of the countries with some of the longest and best glaciological data sets. Its glaciers and their changes in response to climate have been extensively investigated, and the number and quality of related studies are notable. However, a comprehensive review of glacier changes and their impact on the hydrology of glacierised catchments for Switzerland is missing and we use the opportunity provided by the EU-FP7 ACQWA project to review the current state of knowledge about past changes and future projections. We examine the type of models that have been applied to infer glacier evolution and identify knowledge gaps that should be addressed in future research in addition to those indicated in previous publications. Common characteristics in long-term series of projected future glacier runoff are an initial peak followed by a decline, associated with shifts in seasonality, earlier melt onset and reduced summer runoff. However, the quantitative predictions are difficult to compare, as studies differ in terms of model structure, calibration strategies, input data, temporal and spatial resolution as well as future scenarios used for impact studies. We identify two sources of uncertainties among those emerging from recent research, and use simulations over four glaciers to: i) quantify the importance of the correct extrapolation of air temperature, and ii) point at the key role played by debris cover in modulating glacier response.}, author = {Pellicciotti, Francesca and Carenzo, M. and Bordoy, R. and Stoffel, M.}, issn = {0048-9697}, journal = {Science of The Total Environment}, keywords = {Pollution, Waste Management and Disposal, Environmental Chemistry, Environmental Engineering}, pages = {1152--1170}, publisher = {Elsevier}, title = {{Changes in glaciers in the Swiss Alps and impact on basin hydrology: Current state of the art and future research}}, doi = {10.1016/j.scitotenv.2014.04.022}, volume = {493}, year = {2014}, } @article{12636, abstract = {Himalayan glacier tongues are commonly debris covered and they are an important source of melt water. However, they remain relatively unstudied because of the inaccessibility of the terrain and the difficulties in field work caused by the thick debris mantles. Observations of debris-covered glaciers are therefore scarce and airborne remote sensing may bridge the gap between scarce field observations and coarse resolution space-borne remote sensing. In this study we deploy an Unmanned Aerial Vehicle (UAV) before and after the melt and monsoon season (May and October 2013) over the debris-covered tongue of the Lirung Glacier in Nepal. Based on stereo-imaging and the structure for motion algorithm we derive highly detailed ortho-mosaics and digital elevation models (DEMs), which we geometrically correct using differential GPS observations collected in the field. Based on DEM differencing and manual feature tracking we derive the mass loss and the surface velocity of the glacier at a high spatial accuracy. On average, mass loss is limited and the surface velocity is very small. However, the spatial variability of melt rates is very high, and ice cliffs and supra-glacial ponds show mass losses that can be an order of magnitude higher than the average. We suggest that future research should focus on the interaction between supra-glacial ponds, ice cliffs and englacial hydrology to further understand the dynamics of debris-covered glaciers. Finally, we conclude that UAV deployment has large potential in glaciology and it may revolutionize methods currently applied in studying glacier surface features.}, author = {Immerzeel, W.W. and Kraaijenbrink, P.D.A. and Shea, J.M. and Shrestha, A.B. and Pellicciotti, Francesca and Bierkens, M.F.P. and de Jong, S.M.}, issn = {0034-4257}, journal = {Remote Sensing of Environment}, keywords = {Computers in Earth Sciences, Geology, Soil Science}, number = {7}, pages = {93--103}, publisher = {Elsevier}, title = {{High-resolution monitoring of Himalayan glacier dynamics using unmanned aerial vehicles}}, doi = {10.1016/j.rse.2014.04.025}, volume = {150}, year = {2014}, } @article{12637, abstract = {The performance of glaciohydrological models which simulate catchment response to climate variability depends to a large degree on the data used to force the models. The forcing data become increasingly important in high-elevation, glacierized catchments where the interplay between extreme topography, climate, and the cryosphere is complex. It is challenging to generate a reliable forcing data set that captures this spatial heterogeneity. In this paper, we analyze the results of a 1 year field campaign focusing on air temperature and precipitation observations in the Langtang valley in the Nepalese Himalayas. We use the observed time series to characterize both temperature lapse rates (LRs) and precipitation gradients (PGs). We study their spatial and temporal variability, and we attempt to identify possible controlling factors. We show that very clear LRs exist in the valley and that there are strong seasonal differences related to the water vapor content in the atmosphere. Results also show that the LRs are generally shallower than the commonly used environmental lapse rates. The analysis of the precipitation observations reveals that there is great variability in precipitation over short horizontal distances. A uniform valley wide PG cannot be established, and several scale-dependent mechanisms may explain our observations. We complete our analysis by showing the impact of the observed LRs and PGs on the outputs of the TOPKAPI-ETH glaciohydrological model. We conclude that LRs and PGs have a very large impact on the water balance composition and that short-term monitoring campaigns have the potential to improve model quality considerably.}, author = {Immerzeel, W. W. and Petersen, L. and Ragettli, S. and Pellicciotti, Francesca}, issn = {1944-7973}, journal = {Water Resources Research}, keywords = {Water Science and Technology}, number = {3}, pages = {2212--2226}, publisher = {American Geophysical Union}, title = {{The importance of observed gradients of air temperature and precipitation for modeling runoff from a glacierized watershed in the Nepalese Himalayas}}, doi = {10.1002/2013wr014506}, volume = {50}, year = {2014}, } @article{1309, abstract = {We show that weak solutions of the Derrida-Lebowitz-Speer-Spohn (DLSS) equation display infinite speed of support propagation. We apply our method to the case of the quantum drift-diffusion equation which augments the DLSS equation with a drift term and possibly a second-order diffusion term. The proof is accomplished using weighted entropy estimates, Hardy's inequality and a family of singular weight functions to derive a differential inequality; the differential inequality shows exponential growth of the weighted entropy, with the growth constant blowing up very fast as the singularity of the weight becomes sharper. To the best of our knowledge, this is the first example of a nonnegativity-preserving higher-order parabolic equation displaying infinite speed of support propagation.}, author = {Julian Fischer}, journal = {Nonlinear Differential Equations and Applications}, number = {1}, pages = {27 -- 50}, publisher = {Birkhäuser}, title = {{Infinite speed of support propagation for the Derrida-Lebowitz-Speer-Spohn equation and quantum drift-diffusion models}}, doi = {10.1007/s00030-013-0235-0}, volume = {21}, year = {2014}, } @article{1312, abstract = {We derive upper bounds on the waiting time of solutions to the thin-film equation in the regime of weak slippage n ∈ [2, 32\11). In particular, we give sufficient conditions on the initial data for instantaneous forward motion of the free boundary. For n ∈ (2, 32\11), our estimates are sharp, for n = 2, they are sharp up to a logarithmic correction term. Note that the case n = 2 corresponds-with a grain of salt-to the assumption of the Navier slip condition at the fluid-solid interface. We also obtain results in the regime of strong slippage n ∈ (1,2); however, in this regime we expect them not to be optimal. Our method is based on weighted backward entropy estimates, Hardy's inequality and singular weight functions; we deduce a differential inequality which would enforce blowup of the weighted entropy if the contact line were to remain stationary for too long.}, author = {Julian Fischer}, journal = {Archive for Rational Mechanics and Analysis}, number = {3}, pages = {771 -- 818}, publisher = {Springer}, title = {{Upper bounds on waiting times for the Thin-film equation: The case of weak slippage}}, doi = {10.1007/s00205-013-0690-0}, volume = {211}, year = {2014}, } @article{8244, abstract = {Passive immunotherapy with monoclonal antibodies represents a cornerstone of human anticancer therapies, but has not been established in veterinary medicine yet. As the tumor-associated antigen EGFR (ErbB-1) is highly conserved between humans and dogs, and considering the effectiveness of the anti-EGFR antibody cetuximab in human clinical oncology, we present here a “caninized” version of this antibody, can225IgG, for comparative oncology studies. Variable region genes of 225, the murine precursor of cetuximab, were fused with canine constant heavy gamma and kappa chain genes, respectively, and transfected into Chinese hamster ovary (CHO) DUKX-B11 cells. Of note, 480 clones were screened and the best clones were selected according to productivity and highest specificity in EGFR-coated ELISA. Upon purification with Protein G, the recombinant cetuximab-like canine IgG was tested for integrity, correct assembly, and functionality. Specific binding to the surface of EGFR-overexpressing cells was assessed by flow cytometry and immunofluorescence; moreover, binding to canine mammary tissue was demonstrated by immunohistochemistry. In cell viability and proliferation assays, incubation with can225IgG led to significant tumor cell growth inhibition. Moreover, this antibody mediated significant tumor cell killing via phagocytosis in vitro. We thus present here, for the first time, the generation of a canine IgG antibody and its hypothetical structure. On the basis of its cetuximab-like binding site, on the one hand, and the expression of a 91% homologous EGFR molecule in canine cancer, on the other hand, this antibody may be a promising research compound to establish passive immunotherapy in dog patients with cancer.}, author = {Singer, J. and Fazekas, Judit and Wang, W. and Weichselbaumer, M. and Matz, M. and Mader, A. and Steinfellner, W. and Meitz, S. and Mechtcheriakova, D. and Sobanov, Y. and Willmann, M. and Stockner, T. and Spillner, E. and Kunert, R. and Jensen-Jarolim, E.}, issn = {1535-7163}, journal = {Molecular Cancer Therapeutics}, number = {7}, pages = {1777--1790}, publisher = {American Association for Cancer Research}, title = {{Generation of a canine anti-EGFR (ErbB-1) antibody for passive immunotherapy in dog cancer patients}}, doi = {10.1158/1535-7163.mct-13-0288}, volume = {13}, year = {2014}, } @article{845, abstract = {Recombination between double-stranded DNA molecules is a key genetic process which occurs in a wide variety of organisms. Usually, crossing-over (CO) occurs during meiosis between genotypes with 98.0-99.9% sequence identity, because within-population nucleotide diversity only rarely exceeds 2%. However, some species are hypervariable and it is unclear how CO can occur between genotypes with less than 90% sequence identity. Here, we study CO in Schizophyllum commune, a hypervariable cosmopolitan basidiomycete mushroom, a frequently encountered decayer of woody substrates. We crossed two haploid individuals, from the United States and from Russia, and obtained genome sequences for their 17 offspring. The average genetic distance between the parents was 14%, making it possible to study CO at very high resolution. We found reduced levels of linkage disequilibrium between loci flanking the CO sites indicating that they are mostly confined to hotspots of recombination. Furthermore, CO events preferentially occurred in regions under stronger negative selection, in particular within exons that showed reduced levels of nucleotide diversity. Apparently, in hypervariable species CO must avoid regions of higher divergence between the recombining genomes due to limitations imposed by the mismatch repair system, with regions under strong negative selection providing the opportunity for recombination. These patterns are opposite to those observed in a number of less variable species indicating that population genomics of hypervariable species may reveal novel biological phenomena.}, author = {Seplyarskiy, Vladimir B and Logacheva, Maria D and Penin, Aleksey A and Baranová, Maria A and Leushkin, Evgeny V and Demidenko, Natalia V and Klepikova, Anna V and Fyodor Kondrashov and Kondrashov, Alexey S and James, Timothy Y}, journal = {Molecular Biology and Evolution}, number = {11}, pages = {3016 -- 3025}, publisher = {Oxford University Press}, title = {{Crossing-over in a hypervariable species preferentially occurs in regions of high local similarity}}, doi = {10.1093/molbev/msu242}, volume = {31}, year = {2014}, } @article{8458, abstract = {The maintenance of bacterial cell shape and integrity is largely attributed to peptidoglycan, a highly cross-linked biopolymer. The transpeptidases that perform this cross-linking are important targets for antibiotics. Despite this biomedical importance, to date no structure of a protein in complex with an intact bacterial peptidoglycan has been resolved, primarily due to the large size and flexibility of peptidoglycan sacculi. Here we use solid-state NMR spectroscopy to derive for the first time an atomic model of an l,d-transpeptidase from Bacillus subtilis bound to its natural substrate, the intact B. subtilis peptidoglycan. Importantly, the model obtained from protein chemical shift perturbation data shows that both domains—the catalytic domain as well as the proposed peptidoglycan recognition domain—are important for the interaction and reveals a novel binding motif that involves residues outside of the classical enzymatic pocket. Experiments on mutants and truncated protein constructs independently confirm the binding site and the implication of both domains. Through measurements of dipolar-coupling derived order parameters of bond motion we show that protein binding reduces the flexibility of peptidoglycan. This first report of an atomic model of a protein–peptidoglycan complex paves the way for the design of new antibiotic drugs targeting l,d-transpeptidases. The strategy developed here can be extended to the study of a large variety of enzymes involved in peptidoglycan morphogenesis.}, author = {Schanda, Paul and Triboulet, Sébastien and Laguri, Cédric and Bougault, Catherine M. and Ayala, Isabel and Callon, Morgane and Arthur, Michel and Simorre, Jean-Pierre}, issn = {0002-7863}, journal = {Journal of the American Chemical Society}, number = {51}, pages = {17852--17860}, publisher = {American Chemical Society}, title = {{Atomic model of a cell-wall cross-linking enzyme in complex with an intact bacterial peptidoglycan}}, doi = {10.1021/ja5105987}, volume = {136}, year = {2014}, } @article{8459, abstract = {Nuclear magnetic resonance (NMR) is a powerful tool for observing the motion of biomolecules at the atomic level. One technique, the analysis of relaxation dispersion phenomenon, is highly suited for studying the kinetics and thermodynamics of biological processes. Built on top of the relax computational environment for NMR dynamics is a new dispersion analysis designed to be comprehensive, accurate and easy-to-use. The software supports more models, both numeric and analytic, than current solutions. An automated protocol, available for scripting and driving the graphical user interface (GUI), is designed to simplify the analysis of dispersion data for NMR spectroscopists. Decreases in optimization time are granted by parallelization for running on computer clusters and by skipping an initial grid search by using parameters from one solution as the starting point for another —using analytic model results for the numeric models, taking advantage of model nesting, and using averaged non-clustered results for the clustered analysis.}, author = {Morin, Sébastien and Linnet, Troels E and Lescanne, Mathilde and Schanda, Paul and Thompson, Gary S and Tollinger, Martin and Teilum, Kaare and Gagné, Stéphane and Marion, Dominique and Griesinger, Christian and Blackledge, Martin and d’Auvergne, Edward J}, issn = {1367-4803}, journal = {Bioinformatics}, keywords = {Statistics and Probability, Computational Theory and Mathematics, Biochemistry, Molecular Biology, Computational Mathematics, Computer Science Applications}, number = {15}, pages = {2219--2220}, publisher = {Oxford University Press}, title = {{Relax: The analysis of biomolecular kinetics and thermodynamics using NMR relaxation dispersion data}}, doi = {10.1093/bioinformatics/btu166}, volume = {30}, year = {2014}, } @article{8460, abstract = {The function of proteins depends on their ability to sample a variety of states differing in structure and free energy. Deciphering how the various thermally accessible conformations are connected, and understanding their structures and relative energies is crucial in rationalizing protein function. Many biomolecular reactions take place within microseconds to milliseconds, and this timescale is therefore of central functional importance. Here we show that R1ρ relaxation dispersion experiments in magic‐angle‐spinning solid‐state NMR spectroscopy make it possible to investigate the thermodynamics and kinetics of such exchange process, and gain insight into structural features of short‐lived states.}, author = {Ma, Peixiang and Haller, Jens D. and Zajakala, Jérémy and Macek, Pavel and Sivertsen, Astrid C. and Willbold, Dieter and Boisbouvier, Jérôme and Schanda, Paul}, issn = {1433-7851}, journal = {Angewandte Chemie International Edition}, number = {17}, pages = {4312--4317}, publisher = {Wiley}, title = {{Probing transient conformational states of proteins by solid-state R1ρ relaxation-dispersion NMR spectroscopy}}, doi = {10.1002/anie.201311275}, volume = {53}, year = {2014}, } @article{8500, abstract = {The main model studied in this paper is a lattice of pendula with a nearest‐neighbor coupling. If the coupling is weak, then the system is near‐integrable and KAM tori fill most of the phase space. For all KAM trajectories the energy of each pendulum stays within a narrow band for all time. Still, we show that for an arbitrarily weak coupling of a certain localized type, the neighboring pendula can exchange energy. In fact, the energy can be transferred between the pendula in any prescribed way.}, author = {Kaloshin, Vadim and Levi, Mark and Saprykina, Maria}, issn = {0010-3640}, journal = {Communications on Pure and Applied Mathematics}, keywords = {Applied Mathematics, General Mathematics}, number = {5}, pages = {748--775}, publisher = {Wiley}, title = {{Arnol′d diffusion in a pendulum lattice}}, doi = {10.1002/cpa.21509}, volume = {67}, year = {2014}, } @article{8501, abstract = {In this paper, we study small perturbations of a class of non-convex integrable Hamiltonians with two degrees of freedom, and we prove a result of diffusion for an open and dense set of perturbations, with an optimal time of diffusion which grows linearly with respect to the inverse of the size of the perturbation.}, author = {Bounemoura, Abed and Kaloshin, Vadim}, issn = {1609-3321}, journal = {Moscow Mathematical Journal}, keywords = {General Mathematics}, number = {2}, pages = {181--203}, publisher = {Independent University of Moscow}, title = {{Generic fast diffusion for a class of non-convex Hamiltonians with two degrees of freedom}}, doi = {10.17323/1609-4514-2014-14-2-181-203}, volume = {14}, year = {2014}, } @article{852, abstract = {Rapid divergence of gene copies after duplication is thought to determine the fate of the copies and evolution of novel protein functions. However, data on howlong the gene copies continue to experience an elevated rate of evolution remain scarce. Standard theory of gene duplications based on some level of genetic redundancy of gene copies predicts that the period of accelerated evolutionmust end relatively quickly. Using a maximum-likelihood approach we estimate preduplication, initial postduplication, and recent postduplication rates of evolution that occurred in themammalian lineage.Wefind that both gene copies experience a similar in magnitude acceleration in their rate of evolution. The copy located in the original genomic position typically returns to the preduplication rates of evolution in a short period of time. The burst of faster evolution of the copy that is located in a new genomic position typically lasts longer. Furthermore, the fast-evolving copies on average continue to evolve faster than the preduplication rates far longer than predicted by standard theory of gene duplications.We hypothesize that the prolonged elevated rates of evolution are determined by functional properties that were acquired during, or soon after, the gene duplication event. }, author = {Rosello, Oriol P and Fyodor Kondrashov}, journal = {Genome Biology and Evolution}, number = {8}, pages = {1949 -- 1955}, publisher = {Oxford University Press}, title = {{Long-Term asymmetrical acceleration of protein evolution after gene duplication}}, doi = {10.1093/gbe/evu159}, volume = {6}, year = {2014}, } @article{856, abstract = {The emergence of new genes throughout evolution requires rewiring and extension of regulatory networks. However, the molecular details of how the transcriptional regulation of new gene copies evolves remain largely unexplored. Here we show how duplication of a transcription factor gene allowed the emergence of two independent regulatory circuits. Interestingly, the ancestral transcription factor was promiscuous and could bind different motifs in its target promoters. After duplication, one paralogue evolved increased binding specificity so that it only binds one type of motif, whereas the other copy evolved a decreased activity so that it only activates promoters that contain multiple binding sites. Interestingly, only a few mutations in both the DNA-binding domains and in the promoter binding sites were required to gradually disentangle the two networks. These results reveal how duplication of a promiscuous transcription factor followed by concerted cis and trans mutations allows expansion of a regulatory network.}, author = {Pougach, Ksenia S and Voet, Arnout R and Fyodor Kondrashov and Voordeckers, Karin and Christiaens, Joaquin F and Baying, Bianka and Bénès, Vladimı́r and Sakai, Ryo and Aerts, Jan A and Zhu, Bo and Van Dijck, Patrick and Verstrepen, Kevin J}, journal = {Nature Communications}, publisher = {Nature Publishing Group}, title = {{Duplication of a promiscuous transcription factor drives the emergence of a new regulatory network}}, doi = {10.1038/ncomms5868}, volume = {5}, year = {2014}, } @article{863, abstract = {The origins of neural systems remain unresolved. In contrast to other basal metazoans, ctenophores (comb jellies) have both complex nervous and mesoderm-derived muscular systems. These holoplanktonic predators also have sophisticated ciliated locomotion, behaviour and distinct development. Here we present the draft genome of Pleurobrachia bachei, Pacific sea gooseberry, together with ten other ctenophore transcriptomes, and show that they are remarkably distinct from other animal genomes in their content of neurogenic, immune and developmental genes. Our integrative analyses place Ctenophora as the earliest lineage within Metazoa. This hypothesis is supported by comparative analysis of multiple gene families, including the apparent absence of HOX genes, canonical microRNA machinery, and reduced immune complement in ctenophores. Although two distinct nervous systems are well recognized in ctenophores, many bilaterian neuron-specific genes and genes of 'classical' neurotransmitter pathways either are absent or, if present, are not expressed in neurons. Our metabolomic and physiological data are consistent with the hypothesis that ctenophore neural systems, and possibly muscle specification, evolved independently from those in other animals.}, author = {Moroz, Leonid L and Kocot, Kevin M and Citarella, Mathew R and Dosung, Sohn and Norekian, Tigran P and Povolotskaya, Inna and Grigorenko, Anastasia P and Dailey, Christopher A and Berezikov, Eugene and Buckley, Katherine M and Ptitsyn, Andrey A and Reshetov, Denis A and Mukherjee, Krishanu and Moroz, Tatiana P and Bobkova, Yelena V and Yu, Fahong and Kapitonov, Vladimir V and Jurka, Jerzy W and Bobkov, Yuriy V and Swore, Joshua J and Girardo, David O and Fodor, Alexander and Gusev, Fedor E and Sanford, Rachel S and Bruders, Rebecca and Kittler, Ellen L and Mills, Claudia E and Rast, Jonathan P and Derelle, Romain and Solovyev, Victor and Fyodor Kondrashov and Swalla, Billie J and Sweedler, Jonathan V and Rogaev, Evgeny I and Halanych, Kenneth M and Kohn, Andrea B}, journal = {Nature}, number = {7503}, pages = {109 -- 114}, publisher = {Nature Publishing Group}, title = {{The ctenophore genome and the evolutionary origins of neural systems}}, doi = {10.1038/nature13400}, volume = {510}, year = {2014}, } @article{865, abstract = {Research on existing drugs often discovers novel mechanisms of their action and leads to the expansion of their therapeutic scope and subsequent remarketing. The Wnt signaling pathway is of the immediate therapeutic relevance, as it plays critical roles in cancer development and progression. However, drugs which disrupt this pathway are unavailable despite the high demand. Here we report an attempt to identify antagonists of the Wnt-FZD interaction among the library of the FDA-approved drugs. We performed an in silico screening which brought up several potential antagonists of the ligand-receptor interaction. 14 of these substances were tested using the TopFlash luciferase reporter assay and four of them identified as active and specific inhibitors of the Wnt3a-induced signaling. However, further analysis through GTP-binding and β-catenin stabilization assays showed that the compounds do not target the Wnt-FZD pair, but inhibit the signaling at downstream levels. We further describe the previously unknown inhibitory activity of an anti-leprosy drug clofazimine in the Wnt pathway and provide data demonstrating its efficiency in suppressing growth of Wnt-dependent triple-negative breast cancer cells. These data provide a basis for further investigations of the efficiency of clofazimine in treatment of Wnt-dependent cancers.}, author = {Koval, Alexey V and Vlasov, Peter K and Shichkova, Polina and Khunderyakova, S and Markov, Yury and Panchenko, J and Volodina, A and Fyodor Kondrashov and Katanaev, Vladimir L}, journal = {Biochemical Pharmacology}, number = {4}, pages = {571 -- 578}, publisher = {Elsevier}, title = {{Anti leprosy drug clofazimine inhibits growth of triple-negative breast cancer cells via inhibition of canonical Wnt signaling}}, doi = {10.1016/j.bcp.2013.12.007}, volume = {87}, year = {2014}, } @article{892, abstract = {The study of molecular evolution is important because it reveals how protein functions emerge and evolve. Recently, several types of studies indicated that substitutions in molecular evolution occur in a compensatory manner, whereby the occurrence of a substitution depends on the amino acid residues at other sites. However, a molecular or structural basis behind the compensation often remains obscure. Here, we review studies on the interface of structural biology and molecular evolution that revealed novel aspects of compensatory evolution. In many cases structural studies benefit from evolutionary data while structural data often add a functional dimension to the study of molecular evolution.}, author = {Ivankov, Dmitry N and Finkelstein, Alexei V and Fyodor Kondrashov}, journal = {Current Opinion in Structural Biology}, number = {1}, pages = {104 -- 112}, publisher = {Elsevier}, title = {{A structural perspective of compensatory evolution}}, doi = {10.1016/j.sbi.2014.05.004}, volume = {26}, year = {2014}, }