Attractor Metabolic Networks

Background The experimental observations and numerical studies with dissipative metabolic networks have shown that cellular enzymatic activity self-organizes spontaneously leading to the emergence of a Systemic Metabolic Structure in the cell, characterized by a set of different enzymatic reactions always locked into active states (metabolic core) while the rest of the catalytic processes are only intermittently active. This global metabolic structure was verified for Escherichia coli, Helicobacter pylori and Saccharomyces cerevisiae, and it seems to be a common key feature to all cellular organisms. In concordance with these observations, the cell can be considered a complex metabolic network which mainly integrates a large ensemble of self-organized multienzymatic complexes interconnected by substrate fluxes and regulatory signals, where multiple autonomous oscillatory and quasi-stationary catalytic patterns simultaneously emerge. The network adjusts the internal metabolic activities to the external change by means of flux plasticity and structural plasticityMethodology/Principal Findings In order to research the systemic mechanisms involved in the regulation of the cellular enzymatic activity we have studied different catalytic activities of a dissipative metabolic network under different external stimuli. The emergent biochemical data have been analysed using statistical mechanic tools, studying some macroscopic properties such as the global information and the energy of the system. We have also obtained an equivalent Hopfield network using a Boltzmann machine. Our main result shows that the dissipative metabolic network can behave as an attractor metabolic network.Conclusions/Significance We have found that the systemic enzymatic activities are governed by attractors with capacity to store functional metabolic patterns which can be correctly recovered from specific input stimuli. The network attractors regulate the catalytic patterns, modify the efficiency in the connection between the multienzymatic complexes, and stably retain these modifications. Here for the first time, we have introduced the general concept of attractor metabolic network, in which this dynamic behavior is observed.Funding provided by Junta de Andalucia Proyecto de Excelencia P09FQM-4682 and the University-Society grant US11/13 of the UPV/EHU. DAP acknowledges support from project TIN2011-27696-C02-01, Spanish Ministry of Economy and Competitiveness. JMC is supported by Ikerbasque, The Basque Foundation for Science

Metalothionein - imunohistochemický biomarker rakoviny: Meta-analýza

Metallothionein (MT) has been extensively investigated as a molecular marker of various types of cancer. In spite of the fact that numerous reviews have been published in this field, no meta-analytical approach has been performed. Therefore, results of to-date immunohistochemistry-based studies were summarized using meta-analysis in this review. Web of science, PubMed, Embase and CENTRAL databases were searched (up to April 30, 2013) and the eligibility of individual studies and heterogeneity among the studies was assessed. Random and fixed effects model meta-analysis was employed depending on the heterogeneity, and publication bias was evaluated using funnel plots and Eggers tests. A total of 77 studies were included with 8,015 tissue samples (4,631 cases and 3,384 controls). A significantly positive association between MT staining and tumors (vs. healthy tissues) was observed in head and neck (odds ratio, OR 9.95; 95% CI 5.82– 17.03) and ovarian tumors (OR 7.83; 1.09–56.29), and a negative association was ascertained in liver tumors (OR 0.10; 0.03–0.30). No significant associations were identified in breast, colorectal, prostate, thyroid, stomach, bladder, kidney, gallbladder, and uterine cancers and in melanoma. . However, a high degree of inconsistence was observed in several tumor types, including colorectal, kidney and prostate cancer. Despite the ambiguity in some tumor types, conclusive results are provided in the tumors of head and neck, ovary and liver and in relation to the tumor grade and patient survival.Metalothionein (MT) byl rozsáhle zkoumán jako molekulární marker různých typů rakoviny. Navzdory tomu, že v této oblasti byly zveřejněny četné hodnocení , byl proveden meta-analytický postup. Proto výsledky na aktuální studie imunohistochemické bázi byly shrnuty pomocí meta-analýzy v této recenzi. Web of Science, PubMed, Embase a centrálních databází byly vyhledávány (až do 30.dubna 2013) a způsobilosti jednotlivých studií a heterogenity mezi studiích byla hodnocena. Náhodné a fixní efekty modelu meta-analýza byla použita v závislosti na různorodosti, a publikace zaujatost byla hodnocena pomocí trychtýř pozemky a testy Eggers.Celkem 77 studií bylo zahrnuto s 8015 vzorky tkání (4631 případů a 3384 kontrol).Významně pozitivní asociace mezi MT barvení a nádorů (vs. zdravých tkání) byl pozorován v oblasti hlavy a krku (poměr šancí, OR 9,95; 95% CI 5.82- 17,03) a ovariální nádory (OR 7,83, 1,09 - 56,29), a negativní asociace byla zjištěna v jaterních nádorů (OR 0,10; 0,03 - 0,30). Žádné významné asociace byly identifikovány v prsu, tlustého střeva, prostaty, štítné žlázy, žaludku, močového měchýře, ledvin, žlučníku, a rakoviny dělohy a melanomu. , Nicméně, vysoký stupeň nesouladu byl pozorován u několika typů nádorů, včetně tlustého střeva, ledvin a prostaty. Navzdory nejednoznačnosti některých typů nádorů, průkazné výsledky jsou uvedeny v nádorů hlavy a krku, vaječníků a jater a ve vztahu ke stupni nádoru a přežití pacienta