KEGG spider: interpretation of genomics data in the context of the global gene metabolic network

KEGG spider is a web-based tool for interpretation of experimentally derived gene lists in order to gain understanding of metabolism variations at a genomic level. KEGG spider implements a 'pathway-free' framework that overcomes a major bottleneck of enrichment analyses: it provides global models uniting genes from different metabolic pathways. Analyzing a number of experimentally derived gene lists, we demonstrate that KEGG spider provides deeper insights into metabolism variations in comparison to existing methods

KEGG spider: interpretation of genomics data in the context of the global gene metabolic network

KEGG spider is a web-based tool for interpretation of experimentally derived gene lists in order to gain understanding of metabolism variations at a genomic level. KEGG spider implements a 'pathway-free' framework that overcomes a major bottleneck of enrichment analyses: it provides global models uniting genes from different metabolic pathways. Analyzing a number of experimentally derived gene lists, we demonstrate that KEGG spider provides deeper insights into metabolism variations in comparison to existing methods

Probabilistic-Entropic Concept of Sustainable Development of the Example of Territories

Nowadays the problem of sustainable development became one of the topical issues. However, many authors point to conceptual complexity, which is that the concept “sustainable development” includes two terms “development” and “sustainability.” At the same time, each of these terms is treated not unambiguously. It leads to the emergence of different interpretations of sustainable development in relation to specific systems. A new concept of sustainable development of systems is proposed. According to this concept, the sustainable development of a complex multidimensional system will be understood as the dynamics consisting in the presence of a trend of balanced change in the entropies of randomness and self-organization while maintaining an acceptable risk level in multidimensional systems. The proposed concept is approved on practical examples. Dynamics of vector entropy and multidimensional risk of Yekaterinburg and Sverdlovsk regions in 1992–2017 is given

Inverse and forward kinematics and workspace analysis of a novel 5-DOF (3T2R) parallel–serial (hybrid) manipulator:

The proposed study provides a solution of the inverse and forward kinematic problems and workspace analysis for a five-degree-of-freedom parallel–serial manipulator, in which the parallel kinematic chain is made in the form of a tripod and the serial kinematic chain is made in the form of two carriages displaced in perpendicular directions. The proposed manipulator allows to realize five independent movements—three translations and two rotations motion pattern (3T2R). Analytical relationships between the coordinates of the end-effector and five controlled movements provided by manipulator's drives (generalized coordinates) were determined. The approach of reachable workspace calculation was defined with respect to available design constraints of the manipulator based on the obtained algorithms of the inverse and forward kinematics. Case studies are considered based on the obtained algorithms of inverse and forward kinematics. For the inverse kinematic problem, the solution is obtained in accordance with the given laws of position and orientation change of the end-effector, corresponding to the motion along a spiral-helical trajectory. For the forward kinematic problem, various assemblies of the manipulator are obtained at the same given values of the generalized coordinates. An example of reachable workspace designing finalizes the proposed study. Dimensions and extreme values of the end-effector orientation angles are calculated

p63 transcriptionally regulates the expression of matrix metallopeptidase 13

p63 is a transcriptional factor belonging to p53 family of genes. Beside the role in cancer, partially shared with p53 and the other member p73, p63 also plays exclusive roles in development and homeostasis of ectodermal/epidermal-related organs. Here we show that p63 transcriptionally controls the expression of the matrix metallopeptidase 13 (MMP13). p63 binds a p53-like responsive element in the human promoter of MMP13, thus promoting the activation of its transcription. The catalytic activity of MMP13 is required in high invasion capacity of metastatic cancer cells, however, although p63 and MMP13 expression correlates in cancer patients, their co-expression does not predict cancer patient survival. Our results demonstrate that p63 directly controls MMP13 expression

Bioinformatics analysis of the serine and glycine pathway in cancer cells

Serine and glycine are amino acids that provide the essential precursors for the synthesis of proteins, nucleic acids and lipids. Employing 3 subsequent enzymes, phosphoglycerate dehydrogenase (PHGDH), phosphoserine phosphatase (PSPH), phosphoserine aminotransferase 1 (PSAT1), 3-phosphoglycerate from glycolysis can be converted in serine, which in turn can by converted in glycine by serine methyl transferase (SHMT). Besides proving precursors for macromolecules, serine/glycine biosynthesis is also required for the maintenance of cellular redox state. Therefore, this metabolic pathway has a pivotal role in proliferating cells, including cancer cells. In the last few years an emerging literature provides genetic and functional evidences that hyperactivation of serine/glycine biosynthetic pathway drives tumorigenesis. Here, we extend these observations performing a bioinformatics analysis using public cancer datasets. Our analysis highlighted the relevance of PHGDH and SHMT2 expression as prognostic factor for breast cancer, revealing a substantial ability of these enzymes to predict patient survival outcome. However analyzing patient datasets of lung cancer our analysis reveled that some other enzymes of the pathways, rather than PHGDH, might be associated to prognosis. Although these observations require further investigations they might suggest a selective requirement of some enzymes in specific cancer types, recommending more cautions in the development of novel translational opportunities and biomarker identification of human cancers

GeneSet2miRNA: finding the signature of cooperative miRNA activities in the gene lists

GeneSet2miRNA is the first web-based tool which is able to identify whether or not a gene list has a signature of miRNA-regulatory activity. As input, GeneSet2miRNA accepts a list of genes. As output, a list of miRNA-regulatory models is provided. A miRNA-regulatory model is a group of miRNAs (single, pair, triplet or quadruplet) that is predicted to regulate a significant subset of genes from the submitted list. GeneSet2miRNA provides a user friendly dialog-driven web page submission available for several model organisms. GeneSet2miRNA is freely available at http://mips.helmholtz-muenchen.de/proj/gene2mir/

Metabolic effect of TAp63? enhanced glycolysis and pentose phosphate pathway, resulting in increased antioxidant defense

TAp63? is a member of the p53 family, which plays a central role in epithelial cancers. Recently, a role has emerged for p53 family members in cancer metabolic modulation.In order to assess whether TAp63? plays a role in cancer metabolism, we exploited p53-null osteosarcoma Tet-On Saos-2 cells, in which the expression of TAp63? was dependent on doxycycline supplementation to the medium. Metabolomics labeling experiments were performed by incubating the cells in 13C-glucose or 13C15N-glutamine-labeled culture media, as to monitor metabolic fluxes upon induced expression of TAp63?.Induced expression of TAp63? resulted in cell cycle arrest at the G1 phase. From a metabolic standpoint, expression of Tap63? promoted glycolysis and the pentose phosphate pathway, which was uncoupled from nucleotide biosynthesis, albeit prevented oxidative stress in the form of oxidized glutathione. Double 13C-glucose and 13C15N-glutamine metabolic labeling confirmed that induced expression of TAp63? corresponded to a decreased flux of pyruvate to the Krebs cycle and decreased utilization of glutamine for catabolic purposes in the TCA cycle. Results were not conclusive in relation to anabolic utilization of labeled glutamine, since it is unclear to what extent the observed minor TAp63?-dependent increases of glutamine-derived labeling in palmitate could be tied to increased rates of reductive carboxylation and de novo synthesis of fatty acids. Finally, bioinformatics elaborations highlighted a link between patient survival rates and the co-expression of p63 and rate limiting enzymes of the pentose phosphate pathway, G6PD and PGD