Serbische Geschichtspolitik im neuen Jahrtausend : die Gleichzeitigkeit von akademischem Geschichtsrevisionismus und staatlicher Vergangenheitsumdeutung

The geometric relaxation following light absorption of the biliverdin, phycocyanobilin and phytochromobilin tetrapyrrole chromophores of bacterial, cyanobacterial and plant phytochromes has been investigated using density functional theory methods. Considering stereoisomers relevant for both red-absorbing Pr and far-red-absorbing Pfr forms of the photoreceptor, it is found that the initial excited-state evolution is dominated by torsional motion at the C10-C11 bond. This holds true for all three chromophores and irrespective of which configuration the chromophores adopt. This finding suggests that the photochromic cycling of phytochromes between their Pr and Pfr forms, which is known to be governed by Z/E photoisomerizations at the C15-C16 bond, relies on interactions between the chromophore and the protein to prevent photoisomerizations at C10-C11. Further, it is found that the uneven distribution of positive charge between the pyrrole rings is a major factor for the photochemical reactivity of the C10-C11 bond.Original Publication:Angela Strambi and Bo Durbeej, Initial excited-state relaxation of the bilin chromophores of phytochromes: a computational study, 2011, PHOTOCHEMICAL and PHOTOBIOLOGICAL SCIENCES, (10), 4, 569-579.http://dx.doi.org/10.1039/c0pp00307gCopyright: Royal Society of Chemistryhttp://www.rsc.org

Relationship Between The Excited State Relaxation Paths Of Rhodopsin And Isorhodopsin

The pigment Isorhodopsin, an analogue of the visual pigment Rhodopsin, is investigated via quantum-mechanics/molecular-mechanics computations based on an ab initio multiconfigurational quantum chemical, treatment. The limited \u3c5 kcal mol(-1) error found for the spectral parameters allows for a nearly quantitative analysis of the excited-state structure and reactivity of its 9-cis-retinal chromophore. We demonstrate that, similar to Rhodopsin, Isorhodopsin features a shallow photoisomerization path. However, the structure of the reaction coordinate appears to be reversed. In fact, while the coordinate still corresponds to an asynchronous crankshaft motion, the dominant isomerization component involves a counterclockwise, rather than clockwise, twisting of the 9-cis bond. Similarly, the minor component involves a clockwise, rather than counterclockwise, twisting of the 11-trans bond. Ultimately, these results indicate that Rhodopsin and Isorhodopsin relax along a common excited-state potential energy valley starting from opposite ends. The fact that the central and lowest energy region of such valley runs along a segment of the intersection space between the ground and excited states of the protein explains why the pigments decay at distinctive conical intersection structures

Structure Prediction and Validation of the ERK8 Kinase Domain

Extracellular signal-regulated kinase 8 (ERK8) has been already implicated in cell transformation and in the protection of genomic integrity and, therefore, proposed as a novel potential therapeutic target for cancer. In the absence of a crystal structure, we developed a three-dimensional model for its kinase domain. To validate our model we applied a structure- based virtual screening protocol consisting of pharmacophore screening and molecular docking. Experimental characterization of the hit compounds confirmed that a high percentage of the identified scaffolds was able to inhibit ERK8. We also confirmed an ATP competitive mechanism of action for the two best-performing molecules. Ultimately, we identified an ERK8 drug-resistant \u27\u27gatekeeper\u27\u27 mutant that corroborated the predicted molecular binding mode, confirming the reliability of the generated structure. We expect that our model will be a valuable tool for the development of specific ERK8 kinase inhibitors

Extracellular signal-regulated kinase 8 (Erk8) controls estrogen-related receptor alpha cellular localization and inhibits its transcriptional activity.

Erk8 (MAPK15) is a large MAP kinase already implicated in the regulation of the functions of different nuclear receptors and in cellular proliferation and transformation. Here, we identify ERRα as a novel Erk8-interacting protein. As a consequence of such interaction, Erk8 induces Crm1-dependent translocation of ERRα to the cytoplasm and inhibits its transcriptional activity. Also, we identify in Erk8 two LXXLL motifs, typical of agonist-bound nuclear receptor corepressors, as necessary features for this MAP kinase to interact with ERRα and to regulate its cellular localization and transcriptional activity. Ultimately, based on the well-established positive role of ERRα in mammary carcinogenesis, we demonstrate that Erk8 is able to counteract, in immortalized human mammary cells, ERRα activation induced by the EGF receptor pathway, often deregulated in breast cancer. Altogether, these results reveal a novel function for Erk8 as a bona fide ERRα corepressor, involved in the control of its cellular localization by nuclear exclusion, and suggest a key role for this MAP kinase in the biological activities of this nuclear receptor

MAPK15/ERK8 stimulates autophagy by interacting with LC3 and GABARAP proteins

Macroautophagy (hereafter referred to as autophagy) is an evolutionarily conserved catabolic process necessary for normal recycling of cellular constituents and for appropriate response to cellular stress. Although several genes belonging to the core molecular machinery involved in autophagosome formation have been discovered, relatively little is known about the nature of signaling networks controlling autophagy upon intracellular or extracellular stimuli. We discovered ATG8-like proteins (MAP1LC3B, GABARAP and GABARAPL1) as novel interactors of MAPK15/ERK8, a MAP kinase involved in cell proliferation and transformation. Based on the role of these proteins in the autophagic process, we demonstrated that MAPK15 is indeed localized to autophagic compartments and increased, in a kinase-dependent fashion, ATG8- like proteins lipidation, autophagosome formation and SQSTM1 degradation, while decreasing LC3B inhibitory phosphorylation. Interestingly, we also identified a conserved LC3-interacting region (LIR) in MAPK15 responsible for its interaction with ATG8-like proteins, for its localization to autophagic structures and, consequently, for stimulation of the formation of these compartments. Furthermore, we reveal that MAPK15 activity was induced in response to serum and amino-acid starvation and that this stimulus, in turn, required endogenous MAPK15 expression to induce the autophagic process. Altogether, these results suggested a new function for MAPK15 as a regulator of autophagy, acting through interaction with ATG8 family proteins. Also, based on the key role of this process in several human diseases, these results supported the use of this MAP kinase as a potential novel therapeutic target

Estudos Artísticos

Os quinze artigos que aqui se reúnem, nesta edição da Revista Croma, são também as propostas para uma nova política, esclarecida, crítica, e mais exigente. Podem observar-se padrões de intervenção, que partem de algumas dimensões comuns: a interpelação do observador, a criação de novos públicos, a proposta de contribuir para uma mudança alargada, partindo de questões a que não são alheias as problemáticas contemporâneas. As questões de género, a emancipação pós-colonial, a sustentabilidade, as migrações, a massificação, a globalização, o fim das ideologias e a ascensão do populismo, entre outras, constituem os contextos da atualidadeinfo:eu-repo/semantics/publishedVersio

estudos artísticos

A revista Gama, Estudos Artísticos estabeleceu-se como um instrumento para a disseminação do conhecimento em torno da arte e da cultura numa perspetiva que se crê inovadora, e que nos caracteriza: estudar arte e artistas através do olhar formado e privilegiado dos companheiros de profissão. Artistas estudam outros artistas. A revista Gama pertence assim a um projeto de resistência: resistência ao centrismo do artworld, ao esmagamento pelos discursos dominantes, às lógicas de reprodução da legitimação instituída. Há uma característica que prevalece em todos os 28 artigos reunidos na presente edição: a reflexão informada sobre autores e obras de arte, que propõe novas leituras e novas redes de conhecimento. Todas juntas constituem um tecido que descobre sentidos, na sua integração global na nova paisagem cultural.info:eu-repo/semantics/publishedVersio