Design and synthesis of Nrf2-derived hydrocarbon stapled peptides for the disruption of protein-DNA-interactions

Misregulation and mutations of the transcription factor Nrf2 are involved in the development of a variety of human diseases. In this study, we employed the technology of stapled peptides to address a protein-DNA-complex and designed a set of Nrf2-based derivatives. Varying the length and position of the hydrocarbon staple, we chose the best peptide for further evaluation in both fixed and living cells. Peptide 4 revealed significant enrichment within the nucleus compared to its linear counterpart 5, indicating potent binding to DNA. Our studies suggest that these molecules offer an interesting strategy to target activated Nrf2 in cancer cells

Design and synthesis of Nrf2-derived hydrocarbon stapled peptides for the disruption of protein-DNA-interactions

Misregulation and mutations of the transcription factor Nrf2 are involved in the development of a variety of human diseases. In this study, we employed the technology of stapled peptides to address a protein-DNA-complex and designed a set of Nrf2-based derivatives. Varying the length and position of the hydrocarbon staple, we chose the best peptide for further evaluation in both fixed and living cells. Peptide 4 revealed significant enrichment within the nucleus compared to its linear counterpart 5, indicating potent binding to DNA. Our studies suggest that these molecules offer an interesting strategy to target activated Nrf2 in cancer cells

An excitable Rho GTPase signaling network generates dynamic subcellular contraction patterns.

Rho GTPase-based signaling networks control cellular dynamics by coordinating protrusions and retractions in space and time. Here, we reveal a signaling network that generates pulses and propagating waves of cell contractions. These dynamic patterns emerge via self-organization from an activator-inhibitor network, in which the small GTPase Rho amplifies its activity by recruiting its activator, the guanine nucleotide exchange factor GEF-H1. Rho also inhibits itself by local recruitment of actomyosin and the associated RhoGAP Myo9b. This network structure enables spontaneous, self-limiting patterns of subcellular contractility that can explore mechanical cues in the extracellular environment. Indeed, actomyosin pulse frequency in cells is altered by matrix elasticity, showing that coupling of contractility pulses to environmental deformations modulates network dynamics. Thus, our study reveals a mechanism that integrates intracellular biochemical and extracellular mechanical signals into subcellular activity patterns to control cellular contractility dynamics

A survey on tree matching and XML retrieval

International audienceWith the increasing number of available XML documents, numerous approaches for retrieval have been proposed in the literature. They usually use the tree representation of documents and queries to process them, whether in an implicit or explicit way. Although retrieving XML documents can be considered as a tree matching problem between the query tree and the document trees, only a few approaches take advantage of the algorithms and methods proposed by the graph theory. In this paper, we aim at studying the theoretical approaches proposed in the literature for tree matching and at seeing how these approaches have been adapted to XML querying and retrieval, from both an exact and an approximate matching perspective. This study will allow us to highlight theoretical aspects of graph theory that have not been yet explored in XML retrieval

Influenza Report

xv, 298 hlm.; ilus.; 22 c

Influenza report

xv+298hlm.;22c

HIV Medicine: A Medical Texbook

HIV Medicine is an online medical textbook that provides comprehensive and timely information on HIV treatment. Chapters include background information on Acute HIV-1 Infection, and a detailed guide to HIV Therapy. There is also current information about side effects, Lipodystrophy Syndrome, and resistance testing. The online textbook includes an impressive, in-depth index of HIV drugs. Editors Christian Hoffmann and Bernd Sebastian Kamps have years of experience in the medical field and provide free and anonymous access of their text to the public. Collaborators include Nyasha Bakare, MD who has worked at the Research Institute for Genetic and Human Therapy (RIGHT) since 2001, and has been working on the clinical development of a therapeutic HIV vaccine. This Web site is easy to navigate and its layout nicely mirrors the organization of a paper textbook. It will be useful as a research tool for college and graduate students as well as for the layperson who desires more in-depth information on HIV and treatments. Join the mailing list to be notified of new chapters and updates

HIV Medicine 2005

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