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11.
Jana Selent Agnieszka A. Kaczor Ramon Guixà-González Pau Carrió Manuel Pastor Cristian Obiol-Pardo 《Journal of molecular modeling》2013,19(4):1507-1514
Survivin, the smallest inhibitor of apoptosis protein (IAP), is a valid target for cancer research. It mediates both the apoptosis pathway and the cell cycle and has been proposed to form a complex with the cyclin-dependent kinase protein CDK4. The resulting complex transports CDK4 from the cytosol to the nucleus, where CDK4 participates in cell division. Survivin has been recognized as a node protein that interacts with several partners; disruption of the formed complexes can lead to new anticancer compounds. We propose a rational model of the survivin/CDK4 complex that fulfills the experimental evidence and that can be used for structure-based design of inhibitors modifying its interface recognition. In particular, the suggested complex involves the alpha helical domain of survivin and resembles the mode of binding of survivin in the survivin/borealin X-ray structure. The proposed model has been obtained by combining protein–protein docking, fractal-based shape complementarity, electrostatics studies and extensive molecular dynamics simulations. Figure
Proposed model of the survivin/CDK4 complex with a close view of the best model refined through molecular dynamics simulations 相似文献
12.
Marian Cristian Stan Richard Klöpsch Aiswarya Bhaskar Jie Li Stefano Passerini Martin Winter 《Liver Transplantation》2013,3(2):231-238
Mechanochemical synthesis of Cu3P in the presence of n‐dodecane results in a material with a secondary particle size distribution of 10 μm, secondary particles which consist of homogeneously agglomerated 20 nm primary particles. The electrochemical performance of Cu3P with lithium is influenced by the reaction depth, in other words by the lower potential cut‐off. During the electrochemical reaction, the displacement of copper by lithium from the Cu3P structure until the formation of Li3P and Cu deteriorates the capacity retention. Improved performance was obtained when the charge potential was limited to 0.50 V (vs. Li/Li+) and the formation of the LixCu3‐xP phase (0 ≤ × ≤ 2). In this case, when the potential is limited to 0.5 V, the capacity is stable for more than 50 cycles. Acceptable electrochemical performances in Li‐ion cells within the voltage range 0.50–2.0 V (vs. Li/Li+) were shown when Cu3P was used as an anode and Li1.2(Ni0.13Mn0.54Co0.13)O2 and LiNi0.5Mn1.5O4 as positive electrode materials. 相似文献
13.
Alejandro Córdova Rocío Hernández-Gil Cristian Alejandro Córdova-Jiménez Diogo José Cardilli Kellen de Sousa Oliveira José Félix Pérez-Gutiérrez 《Reproductive biology》2013,13(2):166-168
The effect of post-thaw incubation (0 vs. 5 h at 15 °C) and straw size (5 vs. 0.5 ml) on motility, acrosomal integrity and in vitro fertilizing (IVF) capacity of cryopreserved boar spermatozoa was studied. In samples assessed immediately after thawing, no differences were found between the two straw sizes. After 5 h post-thaw incubation, all parameters, except polyspermy, decreased and, spermatozoa packaged in 5 ml straws showed better functional and IVF parameters than these in 0.5 ml straws. 相似文献
14.
Cristian de Sales Dambros Valéria Natália Vasconcelos da Silva Renato Azevedo José Wellington de Morais 《Journal for Nature Conservation》2013,21(5):279-285
Roads and road-building are among the most important environmental impacts on forests near urban areas, but their effects on ecosystem processes and species distributions remain poorly known. Termites are the primary decomposer organisms in tropical forests and their spatial distribution is strongly affected by vegetation and soil structure. We studied the impacts of road construction on termite community structure in an Amazonian forest fragment near Manaus, Brazil. One leading question was whether the fragment under study was large enough to maintain the termite species pool present in nearby continuous forests. We also asked how soil moisture and canopy openness varied with proximity to roads, and whether these changes were associated with changes in termite species richness and composition in the fragment. While the forest fragment had a termite composition very similar to that of continuous forests, roads caused important changes in soil moisture and canopy openness, especially when close to forest edges. At distances of up to 81 m from roads, changes in soil moisture were significantly related to changes in termite species composition, but there was no correlation between canopy openness and species richness or composition. These results suggest that fragmentation caused by roads impacts termites in a different and less damaging manner than fragmentation caused by other kinds of degradation, and that even fragments bisected by roads can support very diverse communities and even undescribed taxa of termites. We conclude that a buffer zone should be established for conservation purposes in the reserves surrounded by roads. 相似文献
15.
16.
Silvio a Beccara Tatjana ?krbi? Roberto Covino Cristian Micheletti Pietro Faccioli 《PLoS computational biology》2013,9(3)
We report on atomistic simulation of the folding of a natively-knotted protein, MJ0366, based on a realistic force field. To the best of our knowledge this is the first reported effort where a realistic force field is used to investigate the folding pathways of a protein with complex native topology. By using the dominant-reaction pathway scheme we collected about 30 successful folding trajectories for the 82-amino acid long trefoil-knotted protein. Despite the dissimilarity of their initial unfolded configuration, these trajectories reach the natively-knotted state through a remarkably similar succession of steps. In particular it is found that knotting occurs essentially through a threading mechanism, involving the passage of the C-terminal through an open region created by the formation of the native -sheet at an earlier stage. The dominance of the knotting by threading mechanism is not observed in MJ0366 folding simulations using simplified, native-centric models. This points to a previously underappreciated role of concerted amino acid interactions, including non-native ones, in aiding the appropriate order of contact formation to achieve knotting. 相似文献
17.
Gianpiero Di Leva Claudia Piovan Pierluigi Gasparini Apollinaire Ngankeu Cristian Taccioli Daniel Briskin Douglas G. Cheung Brad Bolon Laura Anderlucci Hansjuerg Alder Gerard Nuovo Meng Li Marilena V. Iorio Marco Galasso Santhanam Ramasamy Guido Marcucci Danilo Perrotti Kimerly A. Powell Anna Bratasz Michela Garofalo Kenneth P. Nephew Carlo M. Croce 《PLoS genetics》2013,9(3)
18.
Simon A. Schmidt Shana S. Jacob Seong Beom Ahn Thusitha Rupasinghe Jens O. Krömer Alamgir Khan Cristian Varela 《Metabolomics : Official journal of the Metabolomic Society》2013,9(1):173-188
Experimental samples are valuable and can represent a significant investment in time and resources. It is highly desirable at times to obtain as much information as possible from a single sample. This is especially relevant for systems biology approaches in which several ‘omics platforms are studied simultaneously. Unfortunately, each platform has a particular extraction methodology which increases sample number and sample volume requirements when multiple ‘omics are analyzed. We evaluated the integration of a yeast extraction method; specifically we explored whether fractions from a single metabolite extraction could be apportioned to multiple downstream ‘omics analytical platforms. In addition, we examined how variations to a chloroform/methanol yeast metabolite extraction regime influence metabolite recoveries. We show that protein suitable for proteomic analysis can be recovered from a metabolite extraction and that recovery of lipids, while reproducible, are not wholly quantitative. Higher quenching solution temperatures (?30 °C) can be used without significant leakage of intracellular metabolites when lower fermentation temperatures (20 °C) are employed. However, extended residence time in quenching solution, in combination with vigorous washing of quenched cell pellets, leads to extensive leakage of intracellular metabolites. Finally, there is minimal difference in metabolite amounts obtained when metabolite extractions are performed at 4 °C compared to extractions at ?20 °C. The evaluated extraction method delivers material suitable for metabolomic and proteomic analyses from the same sample preparation. 相似文献
19.
Josquin Nys Cristian R. Smulski Aubry Tardivel Laure Willen Christine Kowalczyk Olivier Donzé Bertrand Huard Henry Hess Pascal Schneider 《PloS one》2013,8(4)
Myeloid cells express the TNF family ligands BAFF/BLyS and APRIL, which exert their effects on B cells at different stages of differentiation via the receptors BAFFR, TACI (Transmembrane Activator and CAML-Interactor) and/or BCMA (B Cell Maturation Antigen). BAFF and APRIL are proteins expressed at the cell membrane, with both extracellular and intracellular domains. Therefore, receptor/ligand engagement may also result in signals in ligand-expressing cells via so-called “reverse signalling”. In order to understand how TACI-Fc (atacicept) technically may mediate immune stimulation instead of suppression, we investigated its potential to activate reverse signalling through BAFF and APRIL. BAFFR-Fc and TACI-Fc, but not Fn14-Fc, reproducibly stimulated the ERK and other signalling pathways in bone marrow-derived mouse macrophages. However, these effects were independent of BAFF or APRIL since the same activation profile was observed with BAFF- or APRIL-deficient cells. Instead, cell activation correlated with the presence of high molecular mass forms of BAFFR-Fc and TACI-Fc and was strongly impaired in macrophages deficient for Fc receptor gamma chain. Moreover, a TACI-Fc defective for Fc receptor binding elicited no detectable signal. Although these results do not formally rule out the existence of BAFF or APRIL reverse signalling (via pathways not tested in this study), they provide no evidence in support of reverse signalling and point to the importance of using appropriate specificity controls when working with Fc receptor-expressing myeloid cells. 相似文献
20.
Cristian Koepfli Lincoln Timinao Tiago Antao Alyssa E. Barry Peter Siba Ivo Mueller Ingrid Felger 《PloS one》2013,8(6)