| 1. |
- Hudson, Thomas J., et al.
(author)
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International network of cancer genome projects
- 2010
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Journal article (peer-reviewed)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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| 2. |
- Fritz, Günter, et al.
(author)
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Natural and amyloid self-assembly of S100 proteins : structural basis of functional diversity
- 2010
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In: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 277:22, s. 4578-4590
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Journal article (peer-reviewed)abstract
- The S100 proteins are 10-12 kDa EF-hand proteins that act as central regulators in a multitude of cellular processes including cell survival, proliferation, differentiation and motility. Consequently, many S100 proteins are implicated and display marked changes in their expression levels in many types of cancer, neurodegenerative disorders, inflammatory and autoimmune diseases. The structure and function of S100 proteins are modulated by metal ions via Ca(2+) binding through EF-hand motifs and binding of Zn(2+) and Cu(2+) at additional sites, usually at the homodimer interfaces. Ca(2+) binding modulates S100 conformational opening and thus promotes and affects the interaction with p53, the receptor for advanced glycation endproducts and Toll-like receptor 4, among many others. Structural plasticity also occurs at the quaternary level, where several S100 proteins self-assemble into multiple oligomeric states, many being functionally relevant. Recently, we have found that the S100A8/A9 proteins are involved in amyloidogenic processes in corpora amylacea of prostate cancer patients, and undergo metal-mediated amyloid oligomerization and fibrillation in vitro. Here we review the unique chemical and structural properties of S100 proteins that underlie the conformational changes resulting in their oligomerization upon metal ion binding and ultimately in functional control. The possibility that S100 proteins have intrinsic amyloid-forming capacity is also addressed, as well as the hypothesis that amyloid self-assemblies may, under particular physiological conditions, affect the S100 functions within the cellular milieu.
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| 3. |
- Meister, Anette, et al.
(author)
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Formation of square lamellae by self-assembly of long-chain bolaphospholipids in water
- 2010
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In: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 6:6, s. 1317-1324
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Journal article (peer-reviewed)abstract
- The self-assembly process of the symmetric single-chain polymethylene-1,omega-bis(phosphocholine) (PC-C34-PC) with a chain length of 34 carbon atoms and two polar phosphocholine headgroups when put into water is exclusively driven by hydrophobic interactions of the long alkyl chains. This process leads to the formation of a dense network of helical nanofibers and the formation of a hydrogel (Meister et al. J. Phys. Chem. B, 2008, 112, 4506). In contrast, the single-chain bolalipids tetra-and hexatriacontane-1,omega-diyl-bis[2-(dimethylammonio)ethylphosphate] (Me2PE-Cn-Me2PE, n = 34, 36) and the partly deuterated analogue Me2PE-C11-(CD2)12-C11-Me2PE (dMe(2)PE-C34-Me2PE) form a different type of stable aggregate. In a first step, the self-assembly of these long-chain bolalipids in water at room temperature leads to the formation of a dense network of nanofibers which eventually form a hydrogel. Within one day, the nanofibers transform into square lamellae that grow up to an edge length of about 100 nm. Nanofibers are linked to one or two (opposite) corners of the squares leading to the appearance of a kite-like structure. After one week, all fibers have been transformed into square lamellae which are apparently stacked and form a gel cake. Within several weeks, a more compact cake is formed by syneresis, i.e. the expulsion of water.
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