79,253 research outputs found

    Едвард Козак та Іван Кедрин-Рудницький: до історії взаємин (Edward Kozak and Ivan Kedryn-Rudnytsky: the History of Friendship)

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    У статті систематизовано та проаналізовано публіцистичну та мемуаристичну спадщину Івана Кедрина-Рудницького про життя та творчість Едварда Козака, а також рецепції ЕКА, як митця-карикатуриста, публіцистичної та політичної діяльності І. Кедрина-Рудницького в різних суспільно-культурних реаліях XX ст. (The article systematizes and analyses Ivan Kedryn-Rudnytsky publicistic and memoir heritage devoted to the life and works of Edward Kozak, along with perception of his [Kedryn-Rudnytsky] journalistic and political activities in the XX century. The author indicates that Ivan Kedryn-Rudnytsky and Edward Kozak actively interacted in 1920s-1930s while living in Lviv. In the second half of the XX century Ivan Kedryn and Edward Kozak lived and worked in the USA, where they often met, as a result they often mentioned each other in their articles and works of art. Articles, memoirs, works fiction and art miniatures of Ivan Kedryn as well as caricatures and cartoons of Edward Kozak displayed high intellectual and aesthetic standards for the generation of Ukrainians outside Ukraine in the middle and in the second half of the XX century. Moreover, mutual verbal and visual forms of appraisals affirmed the ingenuity of Edward Kozak and Ivan Kedryn as the best representatives of the Ukrainian creative elite, social, cultural figures and guides for all Ukrainians worldwide outside their homeland

    In Vitro Data Suggest a Role for PMS2 Kozak Sequence Mutations in Lynch Syndrome Risk

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    This study investigates the role of 5′ UTR PMS2 Kozak sequence genetic variation in cancer risk. It accomplishes this through the development of a mid-throughput reporter assay where variants can be tested for protein translation efficiency. The results highlight the importance of continued study of the Kozak sequence related to human disease

    Quantitative global studies reveal differential translational control by start codon context across the fungal kingdom

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    International audienceEukaryotic protein synthesis generally initiates at a start codon defined by an AUG and its surrounding Kozak sequence context, but the quantitative importance of this context in different species is unclear. We tested this concept in two pathogenic Crypto-coccus yeast species by genome-wide mapping of translation and of mRNA 5 and 3 ends. We observed thousands of AUG-initiated upstream open reading frames (uORFs) that are a major contributor to translation repression. uORF use depends on the Kozak sequence context of its start codon, and uORFs with strong contexts promote nonsense-mediated mRNA decay. Transcript leaders in Cryptococcus and other fungi are substantially longer and more AUG-dense than in Saccharomyces. Numerous Crypto-coccus mRNAs encode predicted dual-localized proteins , including many aminoacyl-tRNA synthetases, in which a leaky AUG start codon is followed by a strong Kozak context in-frame AUG, separated by mitochondrial-targeting sequence. Analysis of other fungal species shows that such dual-localization is also predicted to be common in the ascomycete mould, Neurospora crassa. Kozak-controlled regulation is correlated with insertions in translational initiation factors in fidelity-determining regions that contact the initiator tRNA. Thus, start codon context is a signal that quantitatively programs both the expression and the structures of proteins in diverse fungi

    Efficiency of encounter-controlled reaction between diffusing reactants in a finite lattice: topology and boundary effects

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    The role of dimensionality (Euclidean versus fractal), spatial extent, boundary effects and system topology on the efficiency of diffusion-reaction processes involving two simultaneously-diffusing reactants is analyzed. We present numerically-exact values for the mean time to reaction, as gauged by the mean walklength before reactive encounter, obtained via application of the theory of finite Markov processes, and via Monte Carlo simulation. As a general rule, we conclude that for sufficiently large systems, the efficiency of diffusion-reaction processes involving two synchronously diffusing reactants (two-walker case) relative to processes in which one reactant of a pair is anchored at some point in the reaction space (one walker plus trap case) is higher, and is enhanced the lower the dimensionality of the system. This differential efficiency becomes larger with increasing system size and, for periodic systems, its asymptotic value may depend on the parity of the lattice. Imposing confining boundaries on the system enhances the differential efficiency relative to the periodic case, while decreasing the absolute efficiencies of both two-walker and one walker plus trap processes. Analytic arguments are presented to provide a rationale for the results obtained. The insights afforded by the analysis to the design of heterogeneous catalyst systems are also discussed.Comment: 15 pages, 8 figures, uses revtex4, accepted for publication in Physica

    TITER: predicting translation initiation sites by deep learning.

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    MotivationTranslation initiation is a key step in the regulation of gene expression. In addition to the annotated translation initiation sites (TISs), the translation process may also start at multiple alternative TISs (including both AUG and non-AUG codons), which makes it challenging to predict TISs and study the underlying regulatory mechanisms. Meanwhile, the advent of several high-throughput sequencing techniques for profiling initiating ribosomes at single-nucleotide resolution, e.g. GTI-seq and QTI-seq, provides abundant data for systematically studying the general principles of translation initiation and the development of computational method for TIS identification.MethodsWe have developed a deep learning-based framework, named TITER, for accurately predicting TISs on a genome-wide scale based on QTI-seq data. TITER extracts the sequence features of translation initiation from the surrounding sequence contexts of TISs using a hybrid neural network and further integrates the prior preference of TIS codon composition into a unified prediction framework.ResultsExtensive tests demonstrated that TITER can greatly outperform the state-of-the-art prediction methods in identifying TISs. In addition, TITER was able to identify important sequence signatures for individual types of TIS codons, including a Kozak-sequence-like motif for AUG start codon. Furthermore, the TITER prediction score can be related to the strength of translation initiation in various biological scenarios, including the repressive effect of the upstream open reading frames on gene expression and the mutational effects influencing translation initiation efficiency.Availability and implementationTITER is available as an open-source software and can be downloaded from https://github.com/zhangsaithu/titer [email protected] or [email protected] informationSupplementary data are available at Bioinformatics online

    Quantitative nucleotide level analysis of regulation of translation in response to depolarization of cultured neural cells

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    Studies on regulation of gene expression have contributed substantially to understanding mechanisms for the long-term activity-dependent alterations in neural connectivity that are thought to mediate learning and memory. Most of these studies, however, have focused on the regulation of mRNA transcription. Here, we utilized high-throughput sequencing coupled with ribosome footprinting to globally characterize the regulation of translation in primary mixed neuronal-glial cultures in response to sustained depolarization. We identified substantial and complex regulation of translation, with many transcripts demonstrating changes in ribosomal occupancy independent of transcriptional changes. We also examined sequence-based mechanisms that might regulate changes in translation in response to depolarization. We found that these are partially mediated by features in the mRNA sequence—notably upstream open reading frames and secondary structure in the 5′ untranslated region—both of which predict downregulation in response to depolarization. Translationally regulated transcripts are also more likely to be targets of FMRP and include genes implicated in autism in humans. Our findings support the idea that control of mRNA translation plays an important role in response to neural activity across the genome

    Aggregation of dipolar colloidal particles: Geometric effects

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    To understand the importance of confinement and the influence of translational degrees of freedom on aggregation of dipolar colloidal particles, we calculate numerically-exact values for the mean encounter time for two nonspherically symmetric molecules to form a two-molecule cluster, regarded here as a precursor to aggregation. A lattice model is formulated in which the asymmetry of the molecules is accounted for by representing each as a "dimer" in the sense that each molecule is specified to occupy two adjacent lattice sites. The two dimers undergo simultaneous translation, and the mean times for their encounter are determined. Exact numerical results are obtained via application of the theory of finite Markov processes. The results allow one to examine in a detailed way the interplay among such factors as geometrical confinement, system size, translational motion, and specific orientational effects in influencing the aggregation event. The results are compared with previously reported theoretical predictions and experiments on the behavior of dipolar colloidal particles in the presence of an applied magnetic field

    Long-lasting, kin-directed female interactions in a spatially structured wild boar social network

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    We thank W. Jędrzejewski for his support and logistical help in trapping wild boar. We are grateful to R. Kozak, A. Waszkiewicz and many students and volunteers for their help with fieldwork as well as to A. N. Bunevich, T. Borowik and local hunters for providing genetic samples. Genetic analyses were performed in the laboratory of the Department of Science for Nature and Environmental Resources, University of Sassari, Italy, with the help of L. Iacolina and D. Biosa. We are grateful to K. O’Mahony who revised English and to A. Widdig, K. Langergraber and one anonymous reviewer for valuable comments on the earlier version of the manuscript.Peer reviewedPublisher PD
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