Inflammatory responses in epithelia: endotoxin-induced IL-6 secretion and iNOS/NO production are differentially regulated in mouse mammary epithelial cells

<p>Abstract</p> <p>Background</p> <p>IL-6 is a pro-inflammatory cytokine that signals via binding to a soluble or membrane bound receptor, while nitric oxide (NO), an oxidative stress molecule, diffuses through the cell membrane without a receptor. Both mediators signal through different mechanisms, yet they are dependent on NFκB. We proposed that both mediators are co-induced and co-regulated in inflamed mammary epithelial cells.</p> <p>Methods</p> <p>SCp2 mammary epithelial cells were treated with bacterial endotoxin (ET) for different time periods and analyzed for induction of IL-6 secretion and NO production by ELISA and Griess reaction, respectively. The expression of <it>IL-6 </it>and <it>induced NO synthase (iNOS) </it>was assayed by real time PCR and/or western immunoblots, and the activation of NFκB was assayed by immunobinding assay. To investigate the role of mammary cell microenvironment (cell-substratum or interaction of mammary epithelial cell types; critical to mammary development, function, and disease) in modulation of the inflammatory response, SCp2 cells were cultured with or without extracellular matrix (EHS) or in coculture with their myoepithelial counterpart (SCg6), and assayed for ET-induced IL-6 and NO.</p> <p>Results</p> <p>Endotoxin induced NFκB activation at 1 h after ET application. IL-6 secretion and NO production were induced, but with unexpected delay in expression of mRNA for <it>iNOS </it>compared to <it>IL-6</it>. NFκB/p65 activation was transient but NFκB/p50 activation persisted longer. Selective inhibition of NFκB activation by Wedelolactone reduced ET-induced expression of IL-6 mRNA and protein but not iNOS mRNA or NO production, suggesting differences in IL-6 and iNOS regulation via NFκB. SCp2 cells in coculture with SCg6 but not in presence of EHS dramatically induced IL-6 secretion even in the absence of ET. ET-induced NO production was blunted in SCp2/SCg6 cocultures compared to that in SCp2 alone.</p> <p>Conclusions</p> <p>The differential regulation of IL-6 and iNOS together with the differential activation of different NFκB dimers suggest that IL-6 and iNOS are regulated by different NFκB dimers, and differentially regulated by the microenvironment of epithelial cells. The understanding of innate immune responses and inflammation in epithelia and linkage thereof is crucial for understanding the link between chronic inflammation and cancer in epithelial tissues such as the mammary gland.</p

Measuring energy footprint of software features

Abstract—With the proliferation of Software systems and the rise of paradigms such the Internet of Things, Cyber- Physical Systems and Smart Cities to name a few, the energy consumed by software applications is emerging as a major concern. Hence, it has become vital that software engineers have a better understanding of the energy consumed by the code they write. At software level, work so far has focused on measuring the energy consumption at function and application level. In this paper, we propose a novel approach to measure energy consumption at a feature level, cross-cutting multiple functions, classes and systems. We argue the importance of such measurement and the new insight it provides to non-traditional stakeholders such as service providers. We then demonstrate, using an experiment, how the measurement can be done with a combination of tools, namely our program slicing tool (PORBS) and energy measurement tool (Jolinar)

Effect of Substrate Temperature and Target-Substrate Distance on Growth of TiO2 Thin Films by Using DC- Reactive Sputtering Technique

Titanium oxide (TiO2) thin films have been deposited by a DC sputtering technique onto microscope glass slides. The effect of substrate temperature (Ts) and target-substrate distance (Dts) on some optical and electrical properties have been studied each individually. The structure of TiO2 thin films has been improved and became more crystalline when Ts has been increased (from 150 ºC to 250 ºC). The conductivity (ϭ), deposition rate (DR) and average values of grain size (G.S) have been increased with increasing Ts while the values of band gap (Eg) and weight percentage of the anatase phase (WA) have been decreased. The thickness of TiO2 film has been increased from 920 nm to 960 nm with increase Ts while it has been decreased from 960 nm to 680 nm with increase Dts (from 25mm to 35mm). As Dts has been increased, the conductivity ϭ, thickness (d) and average values of grain size have been decreased. The decreasing of conductivity at Dts=35 maybe attributes to increase the weight percentage of the rutile phase (WR). The XRD results show that the TiO2 structure phase has been varied. The results show that the optical and electrical properties of TiO2 film affected by changes the condition parameters especially Ts and Dts as well as the density and energy of the impinging atoms. The surface morphology and component of TiO2 thin films, resistance, optical transmittance and structure of film were characterized by SEM (EDX), I-V meter, UV-VIS spectrophotometer and XRD respectively

Connexins: a myriad of functions extending beyond assembly of gap junction channels

Connexins constitute a large family of trans-membrane proteins that allow intercellular communication and the transfer of ions and small signaling molecules between cells. Recent studies have revealed complex translational and post-translational mechanisms that regulate connexin synthesis, maturation, membrane transport and degradation that in turn modulate gap junction intercellular communication. With the growing myriad of connexin interacting proteins, including cytoskeletal elements, junctional proteins, and enzymes, gap junctions are now perceived, not only as channels between neighboring cells, but as signaling complexes that regulate cell function and transformation. Connexins have also been shown to form functional hemichannels and have roles altogether independent of channel functions, where they exert their effects on proliferation and other aspects of life and death of the cell through mostly-undefined mechanisms. This review provides an updated overview of current knowledge of connexins and their interacting proteins, and it describes connexin modulation in disease and tumorigenesis

Energy saving and energy efficiency of the Belarusian economy: analysis of concepts and evaluation criteria, proposed approaches to improving the energy efficiency of the housing stock

The article analyzes the concepts and indicators for assessing energy saving and energy efficiency, which revealed a clear terminological relationship between the studied concepts and the absence of evaluation criteria that characterize important components of energy efficiency by type of economic activity and economic spheres. The most important components of energy efficiency were identified and calculations confirming the importance of the national policy to improve the energy efficiency of the housing stock as the sector with the highest energy saving potential were made. It was confirmed that in order to achieve high indicators of real economic growth, both consistent and constructive measures are needed to create energy facilities of a new formation, as well as to improve existing capacities and facilities, for example, in the form of major repairs of the housing stock

Characteristics and survival of patients with advanced cancer and p53 mutations.

P53 mutations are associated with invasive tumors in mouse models. We assessed the p53mutations and survival in patients with advanced cancer treated in the Phase I Program. Of 691 tested patients, 273 (39.5%) had p53 mutations. Patients with p53 mutations were older (p&lt;.0001) and had higher numbers of liver metastases (p=.005). P53 mutations were associated with higher numbers of other aberrations; PTEN (p=.0005) and HER2 (p=.003)aberrations were more common in the p53 mutation group. No survival difference was observed between patients with p53 mutations and those with wild-type p53. In patients with wild-type p53 and other aberrations, patients treated with matched-therapy against the additional aberrations had longer survival compared to those treated with non-matched-therapy or those who received no therapy (median survival, 26.0 vs. 11.8 vs. 9.8 months, respectively; p= .0007). Results were confirmed in a multivariate analysis (p= .0002). In the p53 mutation group with additional aberrations, those who received matched-therapy against the additional aberrations had survival similar to those treated with non-matched-therapy or those who received no therapy (p=.15). In conclusion, our results demonstrated resistance to matched-targeted therapy to the other aberrations in patients with p53 mutations and emphasize the need to overcome this resistance