Activation of the E-cadherin/catenin complex in human MCF-7 breast cancer cells by all-trans-retinoic acid.

All-trans-retinoic acid (RA), like insulin-like growth factor I (IGF-I) and tamoxifen, inhibit invasion of human MCF-7/6 mammary cancer cells in vitro. For tamoxifen and for IGF-I, activation of the invasion-suppressor function of the E-cadherin/catenin complex was shown to be the most probable mechanism of the anti-invasive action. We did a series of experiments to determine whether the anti-invasive effect of RA also implicated the invasion-suppressor E-cadherin/catenin complex. Human MCF-7/6 mammary and HCT-8/R1 colon cancer cells, both with a dysfunctional E-cadherin/catenin complex, were treated with RA and the function of the complex was evaluated through Ca(2+)-dependent fast aggregation. Fast aggregation of both MCF-7/6 and HCT-8/R1 cells was induced by 1 microM RA. This effect was abolished by antibodies against E-cadherin. RA-induced fast aggregation was not sensitive to cycloheximide, tyrosine kinase inhibitors or antibodies against IGF-I or against the IGF-I receptor. RA did not stimulate IGF-I receptor phosphorylation or alter the E-cadherin/catenin complex, as evidenced by immunoprecipitation. RA up-regulates the function of the invasion-suppressor complex E-cadherin/catenin. Its action mechanism is different from that of IGF-I. RA may act as an anti-invasive agent with unique mechanisms of action

Diermeel in diervoeders? : een methodische discussie met stakeholders

In dit rapport wordt verslag gedaan van een workshop die ten doel had een beter inzicht te krijgen in de belangen van de Nederlandse samenleving met betrekking tot de vraag of het beleid ten aanzien van dierlijke eiwitten in diervoeders versoepeld kan worden. Daarbij is gebruik maakt van een nieuwe, brede afwegingsmethodiek (TRAK) waarmee het mogelijk is verschillende beleidsscenario's' aan de hand van verschillende waarden te beoordelen en te scoren

Insulin-like growth factor I activates the invasion suppressor function of E-cadherin in MCF-7 human mammary carcinoma cells in vitro.

The calcium-dependent cell-cell adhesion molecule E-cadherin has been shown to counteract invasion of epithelial neoplastic cells. Using three monoclonal antibodies, we have demonstrated the presence of E-cadherin at the surface of human MCF-7/6 mammary carcinoma cells by indirect immunofluorescence coupled to flow cytometry and by immunocytochemistry. Nevertheless, MCF-7/6 cells failed to aggregate in a medium containing 1.25 mM CaCl2, and they were invasive after confrontation with embryonic chick heart fragments in organ culture. Treatment of MCF-7/6 cells with 0.5 microgram ml-1 insulin-like growth factor I (IGF-I) led to homotypic aggregation within 5 to 10 min and inhibited invasion in vitro during at least 8 days. The effect of IGF-I on cellular aggregation was insensitive to cycloheximide. However, monoclonal antibodies that interfered with the function of either the IGF-I receptor (alpha IR3) or E-cadherin (HECD-1, MB2) blocked the effect of IGF-I on aggregation. The effects of IGF-I on aggregation and on invasion could be mimicked by 1 microgram ml-1 insulin, but not by 0.5 microgram ml-1 IGF-II. The insulin effects were presumably not mediated by the IGF-I receptor, since they could not be blocked by an antibody against this receptor (alpha IR3). Our results indicate that IGF-I activates the invasion suppressor role of E-cadherin in MCF-7/6 cells

Thermo-mechanical behavior of a granodiorite from the Liquiñe fractured geothermal system (39°S) in the Southern Volcanic Zone of the Andes

Fractures and faults in granitic rocks play an important role in geothermal systems because they permit the circulation of hot fluids. However, the thermo-hydro-mechanical behavior of granitic rocks has predominantly been studied at temperatures exceeding 300 °C but many geothermal systems experience temperatures much lower than this. The aim of this study was to evaluate how the depth, temperature, and amount and rate of mechanical loading associated conditions, that are realistic in low temperature geothermal system, influence the physical properties of geothermal reservoir hosting rock. We carried out both room temperature and low temperature thermo-mechanical tests on a granodiorite sample from the Liquiñe area, Chile, and performed post-experimental X-ray microtomography analysis to numerically estimate the permeability of the generated fractures. The results showed that both rock strength and rock stiffness decreased with increments of temperature treatment related to the development of thermal crack damage at temperatures > 150 °C and through the development of sub-critical cracking at constant temperatures between 50–75 °C. Slowest deformed samples also exhibited lower strengths, attributed to the development of sub-critical cracking. The cyclic triaxial loading test indicated that significant mechanical fracture damage was only initiated above 80% of the peak stress regardless of the number of repeated loading cycles at lower stresses. Low-temperature treatment appears to be a conditioning factor, but not the dominant factor in controlling the physical properties of reservoir hosting rocks. Our findings indicate that thermal crack damage is likely important for developing microfracture related permeability at depths between around 2–6 km where the temperature is sufficiently high to induce thermal cracking. At shallower depths, such was previously estimated the reservoir of Liquiñe, thermal crack damage is only generated adjacent to fractures that remain open and circulate the hot fluids but sub-critical cracking over time reduces the strength of rocks in lower temperature regimes. These processes combined to produce a geothermal reservoir in Liquiñe which likely first required the presence of a highly fractured fault zone

Antioxidant, antiinflammatory and antiinvasive activities of biopolyphenolics

n/

The effect of cigarette smoke exposure on the development of inflammation in lungs, gut and joints of TNFΔARE mice

The inflammatory cytokine TNF-alpha is a central mediator in many immune-mediated diseases, such as Crohn's disease (CD), spondyloarthritis (SpA) and chronic obstructive pulmonary disease (COPD). Epidemiologic studies have shown that cigarette smoking (CS) is a prominent common risk factor in these TNF-dependent diseases. We exposed TNF Delta ARE mice; in which a systemic TNF-alpha overexpression leads to the development of inflammation; to 2 or 4 weeks of air or CS. We investigated the effect of deregulated TNF expression on CS-induced pulmonary inflammation and the effect of CS exposure on the initiation and progression of gut and joint inflammation. Upon 2 weeks of CS exposure, inflammation in lungs of TNF Delta ARE mice was significantly aggravated. However, upon 4 weeks of CS-exposure, this aggravation was no longer observed. TNF Delta ARE mice have no increases in CD4+ and CD8+ T cells and a diminished neutrophil response in the lungs after 4 weeks of CS exposure. In the gut and joints of TNF Delta ARE mice, 2 or 4 weeks of CS exposure did not modulate the development of inflammation. In conclusion, CS exposure does not modulate gut and joint inflammation in TNF Delta ARE mice. The lung responses towards CS in TNF Delta ARE mice however depend on the duration of CS exposure

Challenges, trends and approaches of future reliability engineering in high precision manufacturing processes

The progress within the development of manufacturing processes leads to complex failure modes and reliability problems within the product life cycle. This fact is valid in the case of mass production of consumer goods, e.g. automobiles, as well as small batch series of industrial goods, e.g. machine tools. Especially micro product platforms with a high amount of derivate and variants are challenging regarding to the planning of high precision manufacturing processes to ensure product reliability. This paper discusses challenges, trends and approaches of future reliability engineering in planning and realisation of high precision manufacturing processes. It considers e.g. mathematical models for uncertainty quantification, additive manufacturing, hydro micro forming, 3D printing and multivariate process validation models. The paper contains contributions of universities, institutes and original equipment manufacturers of industrial nations: Germany, United Kingdom, Japan, Turkey, Poland and U.S.A

Integrating Spatial Educational Experiences (Isee) – Mapping a New Approach to Teaching and Learning Soil Science

The purpose of the Integrating Spatial Educational Experiences project is to develop the ability of our students to use digital maps: (1) to learn how and why soils and landscapes vary spatially at scales ranging from fields, to counties, states, and globally and (2) to learn how the spatial distribution of soils and landscapes impacts the distributions of land use, and environmental and ecosystem services across various scales. Our immediate audience is undergraduate students in soil, crop, natural resource, and environmental science curricula in colleges and universities, but the products created by this project will have broader uses for outreach to other clientele. Products to support teaching and learning include: (1) a revised and expanded Integrating Spatial Educational Experiences (Isee) web site, (2) maps of soil properties for Indiana, West Virginia, Ohio, Kentucky, Illinois, Wisconsin, and Texas, (3) a community of practice dedicated to Integrating Spatial Educational Experiences in soil science education on STEMEdhub.org, and (4) lessons, worksheets, exercises, and experiences shared with the Isee community of practice