34 research outputs found

    Drug-induced eRF1 degradation promotes readthrough and reveals a new branch of ribosome quality control.

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    Suppression of premature termination codons (PTCs) by translational readthrough is a promising strategy to treat a wide variety of severe genetic diseases caused by nonsense mutations. Here, we present two potent readthrough promoters-NVS1.1 and NVS2.1-that restore substantial levels of functional full-length CFTR and IDUA proteins in disease models for cystic fibrosis and Hurler syndrome, respectively. In contrast to other readthrough promoters that affect stop codon decoding, the NVS compounds stimulate PTC suppression by triggering rapid proteasomal degradation of the translation termination factor eRF1. Our results show that this occurs by trapping eRF1 in the terminating ribosome, causing ribosome stalls and subsequent ribosome collisions, and activating a branch of the ribosome-associated quality control network, which involves the translational stress sensor GCN1 and the catalytic activity of the E3 ubiquitin ligases RNF14 and RNF25

    GeoDTN: Geographic routing in disruption tolerant networks, in

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    Abstract-In this paper we present a disruption tolerant routing algorithm based on geographic location information, which improves upon the hop count compared to the current state of the art by up to a factor of three in large scale human networks. Leveraging only the history of geographic movement patterns in the two-hop neighborhood, our algorithm is able to perform well in the absence of knowledge of social interaction between nodes and without detailed future schedule information. Representing previously visited locations as probability distributions encoded in an efficient vector, we formalize a heuristic for efficiently forwarding messages in disruption tolerant networks, implement a framework for comparing our approach with the state of the art, and evaluate key metrics, such as hop count and delivery rate, as well as energy consumption and battery depletion fairness on real world data. We are able to outperform the state of the art in human mobility based networks considerably in terms of energy usage per node, thereby extending data network availability further into areas devoid of otherwise necessary communication infrastructure

    SimBetAge: Utilizing Temporal Changes in Social Networks for Delay/Disconnection Tolerant Networking

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    In this paper, we present SimBetAge, an extension to Sim-Bet taking into account the gradual aging of connections in social networks which thereby increases the performance by an order of magnitude, especially in evolving network structures. For this purpose, we redefine similarity and betweenness to make use of weighted social network graphs