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51.
Xiaoke Ma Long Gao Georgios Karamanlidis Peng Gao Chi Fung Lee Lorena Garcia-Menendez Rong Tian Kai Tan 《PLoS computational biology》2015,11(6)
Development of heart diseases is driven by dynamic changes in both the activity and connectivity of gene pathways. Understanding these dynamic events is critical for understanding pathogenic mechanisms and development of effective treatment. Currently, there is a lack of computational methods that enable analysis of multiple gene networks, each of which exhibits differential activity compared to the network of the baseline/healthy condition. We describe the iMDM algorithm to identify both unique and shared gene modules across multiple differential co-expression networks, termed M-DMs (multiple differential modules). We applied iMDM to a time-course RNA-Seq dataset generated using a murine heart failure model generated on two genotypes. We showed that iMDM achieves higher accuracy in inferring gene modules compared to using single or multiple co-expression networks. We found that condition-specific M-DMs exhibit differential activities, mediate different biological processes, and are enriched for genes with known cardiovascular phenotypes. By analyzing M-DMs that are present in multiple conditions, we revealed dynamic changes in pathway activity and connectivity across heart failure conditions. We further showed that module dynamics were correlated with the dynamics of disease phenotypes during the development of heart failure. Thus, pathway dynamics is a powerful measure for understanding pathogenesis. iMDM provides a principled way to dissect the dynamics of gene pathways and its relationship to the dynamics of disease phenotype. With the exponential growth of omics data, our method can aid in generating systems-level insights into disease progression. 相似文献
52.
Sangkyun Lee Amalia Papanikolaou Georgios A. Keliris Stelios M. Smirnakis 《Journal of visualized experiments : JoVE》2015,(96)
Visual cortex is retinotopically organized so that neighboring populations of cells map to neighboring parts of the visual field. Functional magnetic resonance imaging allows us to estimate voxel-based population receptive fields (pRF), i.e., the part of the visual field that activates the cells within each voxel. Prior, direct, pRF estimation methods1 suffer from certain limitations: 1) the pRF model is chosen a-priori and may not fully capture the actual pRF shape, and 2) pRF centers are prone to mislocalization near the border of the stimulus space. Here a new topographical pRF estimation method2 is proposed that largely circumvents these limitations. A linear model is used to predict the Blood Oxygen Level-Dependent (BOLD) signal by convolving the linear response of the pRF to the visual stimulus with the canonical hemodynamic response function. PRF topography is represented as a weight vector whose components represent the strength of the aggregate response of voxel neurons to stimuli presented at different visual field locations. The resulting linear equations can be solved for the pRF weight vector using ridge regression3, yielding the pRF topography. A pRF model that is matched to the estimated topography can then be chosen post-hoc, thereby improving the estimates of pRF parameters such as pRF-center location, pRF orientation, size, etc. Having the pRF topography available also allows the visual verification of pRF parameter estimates allowing the extraction of various pRF properties without having to make a-priori assumptions about the pRF structure. This approach promises to be particularly useful for investigating the pRF organization of patients with disorders of the visual system. 相似文献
53.
Michel Guipponi Federico A. Santoni Vincent Setola Corinne Gehrig Maud Rotharmel Macarena Cuenca Olivier Guillin Dimitris Dikeos Georgios Georgantopoulos George Papadimitriou Logos Curtis Alexandre Méary Franck Schürhoff Stéphane Jamain Dimitri Avramopoulos Marion Leboyer Dan Rujescu Ann Pulver Dominique Campion David P. Siderovski Stylianos E. Antonarakis 《PloS one》2015,10(10)
54.
Georgios Hadjigeorgiou Efthimios Dardiotis Georgios Tsivgoulis Triantafyllos Doskas Damianos Petrou Nikolaos Makris Nikolaos Vlaikidis Thomas Thomaidis Athanasios Kyritsis Nikolaos Fakas Xoulietta Treska Clementine Karageorgiou Stefania Sotirli Christos Giannoulis Dimitra Papadimitriou Ioannis Mylonas Evaggelos Kouremenos George S. Vlachos Dimitrios Georgiopoulos Despoina Mademtzoglou Michalis Vikelis Elias Zintzaras 《PloS one》2015,10(10)
55.
Georgios Tzelepis Akira Hosomi Tanim Jabid Hossain Hiroto Hirayama Mukesh Dubey Dan Funck Jensen Tadashi Suzuki Magnus Karlsson 《Biochemical and biophysical research communications》2014
N-Glycosylation is an important post-translational modification of proteins, which mainly occurs in the endoplasmic reticulum (ER). Glycoproteins that are unable to fold properly are exported to the cytosol for degradation by a cellular system called ER-associated degradation (ERAD). Once misfolded glycoproteins are exported to the cytosol, they are subjected to deglycosylation by peptide:N-glycanase (PNGase) to facilitate the efficient degradation of misfolded proteins by the proteasome. Interestingly, the ortholog of PNGase in some filamentous fungi was found to be an inactive deglycosylating enzyme. On the other hand, it has been shown that in filamentous fungi genomes, usually two different fungi-specific endo-β-N-acetylglucosamidases (ENGases) can be found; one is predicted to be localized in the cytosol and the other to have a signal sequence, while the functional importance of these enzymes remains to be clarified. In this study the ENGases of the filamentous fungus Trichoderma atroviride was characterized. By heterologous expression of the ENGases Eng18A and Eng18B in Saccharomyces cerevisiae, it was found that both ENGases are active deglycosylating enzymes. Interestingly, only Eng18B was able to enhance the efficient degradation of the RTL protein, a PNGase-dependent ERAD substrate, implying the involvement of this enzyme in the ERAD process. These results indicate that T. atroviride Eng18B may deglycosylate misfolded glycoproteins, substituting the function of the cytoplasmic PNGase in the ERAD process. 相似文献
56.
Thomas M. Koutsos Georgios C. Dimopoulos Andreas P. Mamolos 《Ecological Engineering》2010,36(8):1017-1027
The main purpose of this study was the development of an impact evaluation model to effectively assess and map possible ecological impacts due to a dam construction on habitats and species from the nearest Natura 2000 sites. A new approach has been developed in order to assess and map possible impacts on habitats due to a dam construction at both construction and operation phase. This methodology includes procedures in order to assess impacts and by calculating evaluation scores. Using Geographical Information Systems (GIS) evaluation scores were assigned to grouped habitat regions at construction and operation dam phase. The construction may affect the presence of the species Lutra at the site near the river but will have no effect at the area where the dam basin and the Natura 2000 site intersect. The other species are not expected to be affected from the dam construction. During the operation phase, the presence of water will influence species like Bombina in a very positive way. The dam operation itself will not have negative effects on the rest of habitats but due to the presence of water, factors like a possible increase on traffic and population may affect negatively the habitats especially near the village areas. The proposed methodology offers an alternative point of view on impact assessment and it is expected to serve as become a valuable tool for decision makers to evaluate potential impacts to threatened species and habitats due to a technical project at construction and operation phase. 相似文献
57.
58.
von Blume J Knippschild U Dequiedt F Giamas G Beck A Auer A Van Lint J Adler G Seufferlein T 《The EMBO journal》2007,26(22):4619-4633
Protein kinase D2 (PKD2), a member of the PKD family of serine/threonine kinases, is localized in various subcellular compartments including the nucleus where the kinase accumulates upon activation of G-protein-coupled receptors. We define three critical post-translational modifications required for nuclear accumulation of PKD2 in response to activation of the CCK2 receptor (CCK2R): phosphorylation at Ser706 and Ser710 within the activation loop by PKC eta leading to catalytic activity and phosphorylation at Ser244 within the zinc-finger domain, which is crucial for blocking nuclear export of active PKD2 by preventing its interaction with the Crm-1 export machinery. We identify CK1delta and epsilon as upstream activated kinases by CCK2R that phosphorylate PKD2 at Ser244. Moreover, nuclear accumulation of active PKD2 is a prerequisite for efficient phosphorylation of its nuclear substrate, HDAC7. Only nuclear, active PKD2 mediates CCK2R-induced HDAC7 phosphorylation and Nur77 expression. Thus, we define a novel, compartment-specific signal transduction pathway downstream of CCK2R that phosphorylates PKD2 at three specific sites, results in nuclear accumulation of the active kinase and culminates in efficient phosphorylation of nuclear PKD2 substrates in human gastric cancer cells. 相似文献
59.
Giamas G Hirner H Shoshiashvili L Grothey A Gessert S Kühl M Henne-Bruns D Vorgias CE Knippschild U 《The Biochemical journal》2007,406(3):389-398
The involvement of CK1 (casein kinase 1) delta in the regulation of multiple cellular processes implies a tight regulation of its activity on many different levels. At the protein level, reversible phosphorylation plays an important role in modulating the activity of CK1delta. In the present study, we show that PKA (cAMP-dependent protein kinase), Akt (protein kinase B), CLK2 (CDC-like kinase 2) and PKC (protein kinase C) alpha all phosphorylate CK1delta. PKA was identified as the major cellular CK1deltaCK (CK1delta C-terminal-targeted protein kinase) for the phosphorylation of CK1delta in vitro and in vivo. This was implied by the following evidence: PKA was detectable in the CK1deltaCK peak fraction of fractionated MiaPaCa-2 cell extracts, PKA shared nearly identical kinetic properties with those of CK1deltaCK, and both PKA and CK1deltaCK phosphorylated CK1delta at Ser370 in vitro. Furthermore, phosphorylation of CK1delta by PKA decreased substrate phosphorylation of CK1delta in vitro. Mutation of Ser370 to alanine increased the phosphorylation affinity of CK1delta for beta-casein and the GST (gluthatione S-transferase)-p53 1-64 fusion protein in vitro and enhanced the formation of an ectopic dorsal axis during Xenopus laevis development. Anchoring of PKA and CK1delta to centrosomes was mediated by AKAP (A-kinase-anchoring protein) 450. Interestingly, pre-incubation of MiaPaCa-2 cells with the synthetic peptide St-Ht31, which prevents binding between AKAP450 and the regulatory subunit RII of PKA, resulted in a 6-fold increase in the activity of CK1delta. In summary, we conclude that PKA phosphorylates CK1delta, predominantly at Ser370 in vitro and in vivo, and that site-specific phosphorylation of CK1delta by PKA plays an important role in modulating CK1delta-dependent processes. 相似文献
60.