257,238 research outputs found

    Translation elongation can control translation initiation on eukaryotic mRNAs

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    Synonymous codons encode the same amino acid, but differ in other biophysical properties. The evolutionary selection of codons whose properties are optimal for a cell generates the phenomenon of codon bias. Although recent studies have shown strong effects of codon usage changes on protein expression levels and cellular physiology, no translational control mechanism is known that links codon usage to protein expression levels. Here, we demonstrate a novel translational control mechanism that responds to the speed of ribosome movement immediately after the start codon. High initiation rates are only possible if start codons are liberated sufficiently fast, thus accounting for the observation that fast codons are overrepresented in highly expressed proteins. In contrast, slow codons lead to slow liberation of the start codon by initiating ribosomes, thereby interfering with efficient translation initiation. Codon usage thus evolved as a means to optimise translation on individual mRNAs, as well as global optimisation of ribosome availability

    Translating inheritance nets to default logic

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    We give a translation of inheritance nets to normal default theories. To avoid discussions about sceptical and credulous reasoning we only regard unambiguous nets but allow explicit exception links restricting the validity of direct links. Contrary to former translations every link will be translated to a "hard" fact of the corresponding default theory while the defaults only repesent the implicit assumptions made when computing the extension of the net. The translation is sound and complete if we restrict the deduction mechanism of default logic appropriately

    Simulation of spontaneous G protein activation reveals a new intermediate driving GDP unbinding

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    Activation of heterotrimeric G proteins is a key step in many signaling cascades. However, a complete mechanism for this process, which requires allosteric communication between binding sites that are ~30 Å apart, remains elusive. We construct an atomically detailed model of G protein activation by combining three powerful computational methods: metadynamics, Markov state models (MSMs), and CARDS analysis of correlated motions. We uncover a mechanism that is consistent with a wide variety of structural and biochemical data. Surprisingly, the rate-limiting step for GDP release correlates with tilting rather than translation of the GPCR-binding helix 5. β-Strands 1 - 3 and helix 1 emerge as hubs in the allosteric network that links conformational changes in the GPCR-binding site to disordering of the distal nucleotide-binding site and consequent GDP release. Our approach and insights provide foundations for understanding disease-implicated G protein mutants, illuminating slow events in allosteric networks, and examining unbinding processes with slow off-rates

    Factorization of Rational Curves in the Study Quadric and Revolute Linkages

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    Given a generic rational curve CC in the group of Euclidean displacements we construct a linkage such that the constrained motion of one of the links is exactly CC. Our construction is based on the factorization of polynomials over dual quaternions. Low degree examples include the Bennett mechanisms and contain new types of overconstrained 6R-chains as sub-mechanisms.Comment: Changed arxiv abstract, corrected some type

    Toggle mechanism for pinching metal tubes

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    A toggle mechanism pinches a metal tube and maintains the tube in a pinched condition, without fracturing. The toggle mechanism includes a plunger translatable along a longitudinal axis, as well as a pair of links pivoted about a common axis extending through an end of the plunger. One of the links also pivots about a fixed axis. A free end of the other link carries a push link which the other link translates at right angles to the plunger longitudinal axis. First and second sides of the tube bear against a first stop block and are engaged by the push link when a compression spring, attached to the plunger, is suddenly released to irreversibly drive the plunger along its longitudinal axis so the pivot point of the two links is driven to an over travel position

    Інтертекстуальність прихованих смислів оповідань селінджера та їх переклад (на матеріалі оповідання Дж. Д. Селінджера «Just before the war with the eskimos»)

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    (uk) У статті розглядаються механізми творення свідомо твореного підтексту оповідання Дж.Д. Селінджера «Just Before the War with the Eskimos». Здійснюється інтерпретація прихованих смислів художнього твору, встановлюються інтертекстуальні зв’язки підтекстів оповідань письменника, аналізуються проблеми, що виникають під час перекладу такого підтексту та пропонуються шляхи їх розв’язання для досягнення максимальної адекватності передачі всіх смислів оповідання.(en) The article deals with the study of the mechanism of the conscious subtext generation in the story by D.J. Salinger «Just Before the War with the Eskimos». The interpretation of hidden senses of the literary text, the identification of the intertextual links of the subtexts of the writer’s works, the analysis of the problems occurring in the course of translation of such a subtext and the ways of their solving to gain the greatest degree of translation adequacy of all the senses of the story are being carried out