Modeling cancer: integration of "omics" information in dynamic systems

The last 10 years have seen the rise of many technologies that produce an unprecedented amount of genome-scale data from many organisms. Although the research community has been successful in exploring these data, many challenges still persist. One of them is the effective integration of such data sets directly into approaches based on mathematical modeling of biological systems. Applications in cancer are a good example. The bridge between information and modeling in cancer can be achieved by two major types of complementary strategies. First, there is a bottom-up approach, in which data generates information about structure and relationship between components of a given system. In addition, there is a top-down approach, where cybernetic and systems-theoretical knowledge are used to create models that describe mechanisms and dynamics of the system. These approaches can also be linked to yield multi-scale models combining detailed mechanism and wide biological scope. Here we give an overall picture of this field and discuss possible strategies to approach the major challenges ahead.     

Testing the utility of Nothofagus pumilio for dating a snow avalanche in Tierra del Fuego, Argentina

In the subalpine forest zone, snow avalanches are potentially stand-devastating disturbances. Historical data regarding past avalanches in Argentina are scarce, but sufficiently old trees can show signs of past avalanche episodes that can be accurately dated using dendrochronological methods. Tree-ring analysis has not yet been used for dating avalanches in Tierra del Fuego, even though these disturbances are important to the dynamics of these southern forests. In this study, we evaluated the quality of Nothofagus pumilio for dating the avalanche that took place in the Martial Valley in 1976. Tree-ring data, complemented with vegetation analysis, was used to study the avalanche path. The dendrochronological study consisted of the analysis of wood samples taken from living trees located on the boundary between the undisturbed forest and the avalanche path. The vegetation analysis compared the forest structure within the avalanche path with the unaffected nearby forest. Wood scars and the abrupt increase in tree growth confirmed the occurrence of an avalanche event in 1976 in the Martial Valley of Tierra del Fuego, Argentina. The vegetation structure within the avalanche path was considerably different than that of the undisturbed forest. We found an important relationship between sapling abundance within the avalanche path and their distance from the undisturbed forest and their altitudinal position. The dendrochronological dating obtained in this research confirmed that the techniques and methodology used for N. pumilio in this study can be successfully applied for dating other avalanches that lack historical information.     

The socioecological complexity of ecological restoration in Mexico

Almost half of Mexican territory has been classified as environmentally degraded. The main response for the last 60 years has been reforestation to combat soil erosion and loss of forest cover, mostly carried out on private lands where negotiations with local stakeholders were critical. Despite four legal instruments referring to ecological restoration, no specific instrument that defines basic concepts, criteria and standards, required actions, or regulations to implement and evaluate ecological restoration exists. The Ministry of the Environment and Natural Resources is now solely in charge of restoration and only recently have external scientists been invited to be part of the process. Following important national and international events in Latin America and the Caribbean region, the First Mexican Symposium on Ecological Restoration was held in November, 2014. This historic event was the first action undertaken in Mexico to meet Objective 3 of the Global Strategy of Plant Conservation, coordinated in Mexico by the National Council for the Use and Knowledge of Biodiversity. Although mangrove ecosystems are the most endangered ecosystem type in Mexico, they were not well represented at the symposium. In contrast, several other ecosystem types, such as tropical dry forest and islands, have received increased attention. Overall, while the Symposium and above‐cited policy initiatives are important steps, Mexico needs to increase its institutional capacities and social organization of the rural sector with regard to ecological restoration. Better integration of social and natural scientists and increased participation of Mexico internationally is also needed.     

Nuclear factor erythroid 2-related factor-2 activity controls 4-hydroxynonenal metabolism and activity in prostate cancer cells

4-Hydroxynonenal (HNE) is an end product of lipoperoxidation with antiproliferative and proapoptotic properties in various tumors. Here we report a greater sensitivity to HNE in PC3 and LNCaP cells compared to DU145 cells. In contrast to PC3 and LNCaP cells, HNE-treated DU145 cells showed a smaller reduction in growth and did not undergo apoptosis. In DU145 cells, HNE did not induce ROS production and DNA damage and generated a lower amount of HNE-protein adducts. DU145 cells had a greater GSH and GST A4 content and GSH/GST-mediated HNE detoxification. Nuclear factor erythroid 2-related factor-2 (Nrf2) is a regulator of the antioxidant response. Nrf2 protein content and nuclear accumulation were higher in DU145 cells compared to PC3 and LNCaP cells, whereas the expression of KEAP1, the main negative regulator of Nrf2 activity, was lower. Inhibition of Nrf2 expression with specific siRNA resulted in a reduction in GST A4 expression and GS-HNE formation, indicating that Nrf2 controls HNE metabolism. In addition, Nrf2 knockdown sensitized DU145 cells to HNE-mediated antiproliferative and proapoptotic activity. In conclusion, we demonstrated that increased Nrf2 activity resulted in a reduction in HNE sensitivity in prostate cancer cells, suggesting a potential mechanism of resistance to pro-oxidant therapy.     

Affinity adsorption of lysozyme on a macroligand prepared with Cibacron Blue 3GA attached to yeast cells

The objective of this study was the development of affinity adsorbent particles with the appropriate characteristics to be applied in protein purification using the affinity ultrafiltration method. To prepare affinity macroligands Cibacron Blue 3GA, as a ligand molecule, was immobilized by covalent bonding onto yeast cell walls, the support material or matrix. The maximum attachment of the ligand to the matrix was 212 μmol/g (ligand dry weight/yeast dry weight). Lysozyme was selected as the protein model for the adsorption studies. Its adsorption onto the matrix without ligand and matrix with attached ligand were investigated batch-wise. The adsorption equilibrium isotherms appeared to follow a typical Langmuir isotherm. The maximum adsorption capacity (q(m)) of the Cell-Cibacron macroligand for lysozyme was 110 mg/ml of wet macroligand. The adsorbent was also employed for the separation of lysozyme from hen egg white. High purity lysozyme was obtained.     

Structure and conformational stability of the enzyme I of Streptomyces coelicolor explored by FTIR and circular dichroism

The bacterial phosphoenolpyruvate (PEP): sugar phosphotransferase system (PTS), formed by a cascade of several proteins, couples the translocation and phosphorylation of specific sugars across cell membranes. The structure and thermal stability of the first protein (enzyme I, EI) of the PTS in Streptomyces coelicolor is studied by using far-UV circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR) at pH 7.0. The deconvolution of FTIR spectra indicates that the protein is mainly composed by a 35% of alpha-helical structure and 30% of beta-sheet. The thermal denaturation curves, as followed by both techniques, show only a midpoint at 330 K. This thermal denaturation behaviour is different to that observed in other members of the EI family.     

Characterization and <Emphasis Type="Italic">in vitro</Emphasis> expression patterns of extracellular degradative enzymes from non-pathogenic binucleate <Emphasis Type="Italic">Rhizoctonia</Emphasis> AG-G

Many filamentous fungi produce an array of extracellular enzymes that acting in cell walls release elicitors of the plant defense response These enzymes may therefore be important in biocontrol applications. The aim of this study was to characterize extracellular degradative enzymes produced by a non-pathogenic binucleate isolate of Rhizoctonia AG-G. The fungus was grown in liquid culture supplemented with pectin, polygalacturonic acid or glucose as a carbon sources and filtrates of the culture media were analyzed for the detection of pectinolytic and glucan hydrolytic enzymes. Using only pectin as a carbon source, secretion of polygalacturonases and methylesterases was found. When the liquid medium was supplemented with polygalacturonic acid, only polygalacturonase activity was detected. However, when glucose was used as carbon source -1,3 and -1,6 glucanases activities were detected, using laminarin and pustulan as substrates, but none of the pectinolytic activities were found. These enzymes were partially purified and characterized. The -(1,3)(1,6) glucanase and polygalacturonase enzymes showed to be active against cell wall polysaccharides from potato sprouts. These enzymes may have an important role in fungus-plant cell wall interaction. This is the first study about the production of extracellular enzymes by non-pathogenic binucleate Rhizoctonia AG-G.