Polynuclear aromatic hydrocarbon carcinogens as antiestrogens in MCF-7 human breast cancer cells: role of the Ah receptor

Treatment of MCF-7 cells with 1.0 μM 3-methylcholanthrene (MC) caused a decrease in cell proliferation and [3H]thymidine uptake whereas no effects were observed at a lower (0.1 μM) concentration. Co-treatment of the cells with 1 nM 17β-estradiol plus 0.1 or 1.0 μ MC resulted in a significant inhibition of 17β-estradiol-induced growth and [3H]thymidine uptake. MC also inhibited the 17β-estradiol-induced secretion of the 52 kDa protein (procathepsin D) in MCF-7 cells and caused a concentration-dependent decrease in the nuclear estrogen receptor (ER) as determined by either velocity sedimentation analysis or immunoquantitation with human ER antibodies. The effects of several different polynuclear aromatic hydrocarbon (PAH) congeners on the nuclear ER in MCF-7 cells were also determined. Only those congeners which bound to the aryl hydrocarbon (Ah) receptor, namely benzo[a]pyrene, benz[a]anthracene, 7,12-dimethylbenz[a]anthracene and MC, caused a decrease in nuclear ER levels. In contrast, benzo[ghi]perylene, a congener which did not bind to the Ah receptor did not affect nuclear ER levels in MCF-7 cells. Moreover, with some congeners the decrease in nuclear ER levels could be observed without any significant induction of ethoxyresorufin O-deethylase activity, a P4501A1-dependent monooxygenase. These data suggest that the Ah receptor liganded with MC and related PAHs induced a broad spectrum of antiestrogenic responses in MCF-7 cells and complements the results of previous studies which report the antiestrogenic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and other halogenated aromatics which are also Ah receptor agonists

Factors underlying membrane potential-dependent and -independent fluorescence responses of potentiometric dyes in stressed cells: diS-C3(3) in yeast

AbstractThe redistribution fluorescent dye diS-C3(3) responds to yeast plasma membrane depolarisation or hyperpolarisation by Δψ-dependent outflow from or uptake into the cells, reflected in changes in the fluorescence maximum λmax and fluorescence intensity. Upon membrane permeabilisation the dye redistributes between the cell and the medium in a purely concentration-dependent manner, which gives rise to Δψ-independent fluorescence responses that may mimic Δψ-dependent blue or red shift in λmax. These λmax shifts after cell permeabilisation depend on probe and ion concentrations inside and outside the cells at the moment of permeabilisation and reflect (a) permeabilisation-induced Δψ collapse, (b) changing probe binding capacity of cell constituents (inverse to the ambient ionic strength) and (c) hampering of probe equilibration by the poorly permeable cell wall. At low external ion concentrations, cell permeabilisation causes ion outflow and probe influx (hyperpolarisation-like red shift in λmax) caused by an increase in the probe-binding capacity of the cell interior and, in the case of heat shock, protein denaturation unmasking additional probe-binding sites. At high external ion levels minimising net ion efflux and at high intracellular probe concentrations at the moment of permeabilisation, the Δψ collapse causes a blue λmax shift mimicking an apparent depolarisation

How Do Price Minimizing Behaviors Impact Smoking Cessation? Findings from the International Tobacco Control (ITC) Four Country Survey

This paper examines how price minimizing behaviors impact efforts to stop smoking. Data on 4,988 participants from the International Tobacco Control Policy Evaluation (ITC) Four-Country Survey who were smokers at baseline (wave 5) and interviewed at a 1 year follow-up were used. We examined whether price minimizing behaviors at baseline predicted: (1) cessation, (2) quit attempts, and (3) successful quit attempts at one year follow up using multivariate logistic regression modeling. A subset analysis included 3,387 participants who were current smokers at waves 5 and 6 and were followed through wave 7 to explore effects of changing purchase patterns on cessation. Statistical tests for interaction were performed to examine the joint effect of SES and price/tax avoidance behaviors on cessation outcomes. Smokers who engaged in any price/tax avoidance behaviors were 28% less likely to report cessation. Persons using low/untaxed sources were less likely to quit at follow up, those purchasing cartons were less likely to make quit attempts and quit, and those using discount cigarettes were less likely to succeed, conditional on making attempts. Respondents who utilized multiple behaviors simultaneously were less likely to make quit attempts and to succeed. SES did not modify the effects of price minimizing behaviors on cessation outcomes. The data from this paper indicate that the availability of lower priced cigarette alternatives may attenuate public health efforts aimed at to reduce reducing smoking prevalence through price and tax increases among all SES groups

Socio-Economic Variation in Price Minimizing Behaviors: Findings from the International Tobacco Control (ITC) Four Country Survey

This paper examines how socio-economic status (SES) modifies how smokers adjust to changes in the price of tobacco products through utilization of multiple price minimizing techniques. Data come from the International Tobacco Control Policy Evaluation (ITC) Four Country Survey, nationally representative samples of adult smokers and includes respondents from Canada, the United States, the United Kingdom and Australia. Cross-sectional analyses were completed among 8,243 respondents (7,038 current smokers) from the survey wave conducted between October 2006 and February 2007. Analyses examined predictors of purchasing from low/untaxed sources, using discount cigarettes or roll-your-own (RYO) tobacco, purchasing cigarettes in cartons, and engaging in high levels of price and tax avoidance at last purchase. All analyses tested for interactions with SES and were weighted to account for changing and under-represented demographics. Relatively high levels of price and tax avoidance behaviors were present; 8% reported buying from low or untaxed source; 36% used discount or generic brands, 13.5% used RYO tobacco, 29% reported purchasing cartons, and 63% reported using at least one of these high price avoidance behaviors. Respondents categorized as having low SES were approximately 26% less likely to report using low or untaxed sources and 43% less likely to purchase tobacco by the carton. However, respondents with low SES were 85% more likely to report using discount brands/RYO compared to participants with higher SES. Overall, lower SES smokers were 25% more likely to engage in at least one or more tax avoidance behaviors compared to their higher SES counterparts. Price and tax avoidance behaviors are relatively common among smokers of all SES strata, but strategies differed with higher SES groups more likely to report traveling to a low-tax location to avoid paying higher prices, purchase duty free tobacco, and purchase by cartons instead of packs all of which were less commonly reported by low SES smokers. Because of the strategies lower SES respondents are more likely to use, reducing price differentials between discount and premium brands may have a greater impact on them, potentially increasing the likelihood of quitting

Carotid artery blowout producing massive hematemesis in the emergency department

AbstractCarotid blowout syndrome (CBS) is a rare and fatal complication which arises from patients who have been treated for head and neck cancer. The incidence of CBS is rare and not commonly seen by emergency physicians. We review a case of a 68-year-old woman with a history of laryngectomy and chemo-radiation therapy presenting with massive oral bleeding and hypotension. Her course and treatments are highlighted, literature referring to CBS are described and we reintroduce the approach of managing such a patient in the emergency department

Collective and fractal properties of pion jets in the four-velocity space at intermediate energies

Experimental results are presented for study of collective and fractal properties of soft pion jets in the space of relative four-dimensional velocities. Significant decreasing is obtained for mean square of second particle distances from jet axis for pion-proton interactions at initial energies $\sim 3$ GeV in comparison with hadron-nuclear collisions at close energies. The decreasing results in power dependence of distance variable on collision energy for range $\sim 2 - 4$ GeV. The observation allows us to estimate the low boundary of manifestation of color degree of freedom in pion jet production. Cluster dimension values were deduced for pion jets in various reactions. Fractional values of this dimension indicate on the manifestation of fractal-like properties by pion jets. Changing of mean kinetic energy of jet particles and fractal dimension with initial energy increasing is consistent with suggestion for presence of color degrees of freedom in pion jet production at intermediate energies.Comment: The conference "Physics of fundamental interactions". ITEP, Moscow, Russia. November 23 - 27, 200

The quorum-sensing molecules farnesol/homoserine lactone and dodecanol operate via distinct modes of action in Candida albicans

Living as a commensal, Candida albicans must adapt and respond to environmental cues generated by the mammalian host and by microbes comprising the natural flora. These signals have opposing effects on C. albicans, with host cues promoting the yeast-to-hyphal transition and bacteria-derived quorum-sensing molecules inhibiting hyphal development. Hyphal development is regulated through modulation of the cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway, and it has been postulated that quorum-sensing molecules can affect filamentation by inhibiting the cAMP pathway. Here, we show that both farnesol and 3-oxo-C12-homoserine lactone, a quorum-sensing molecule secreted by Pseudomonas aeruginosa, block hyphal development by affecting cAMP signaling; they both directly inhibited the activity of the Candida adenylyl cyclase, Cyr1p. In contrast, the 12-carbon alcohol dodecanol appeared to modulate hyphal development and the cAMP signaling pathway without directly affecting the activity of Cyr1p. Instead, we show that dodecanol exerted its effects through a mechanism involving the C. albicans hyphal repressor, Sfl1p. Deletion of SFL1 did not affect the response to farnesol but did interfere with the response to dodecanol. Therefore, quorum sensing in C. albicans is mediated via multiple mechanisms of action. Interestingly, our experiments raise the possibility that the Burkholderia cenocepacia diffusible signal factor, BDSF, also mediates its effects via Sfl1p, suggesting that dodecanol's mode of action, but not farnesol or 3-oxo-C12-homoserine lactone, may be used by other quorum-sensing molecules

Kleene Algebras and Semimodules for Energy Problems

With the purpose of unifying a number of approaches to energy problems found in the literature, we introduce generalized energy automata. These are finite automata whose edges are labeled with energy functions that define how energy levels evolve during transitions. Uncovering a close connection between energy problems and reachability and B\"uchi acceptance for semiring-weighted automata, we show that these generalized energy problems are decidable. We also provide complexity results for important special cases

Fermionic response from fractionalization in an insulating two-dimensional magnet

Conventionally ordered magnets possess bosonic elementary excitations, called magnons. By contrast, no magnetic insulators in more than one dimension are known whose excitations are not bosons but fermions. Theoretically, some quantum spin liquids (QSLs) -- new topological phases which can occur when quantum fluctuations preclude an ordered state -- are known to exhibit Majorana fermions as quasiparticles arising from fractionalization of spins. Alas, despite much searching, their experimental observation remains elusive. Here, we show that fermionic excitations are remarkably directly evident in experimental Raman scattering data across a broad energy and temperature range in the two-dimensional material $\alpha$-RuCl$_3$. This shows the importance of magnetic materials as hosts of Majorana fermions. In turn, this first systematic evaluation of the dynamics of a QSL at finite temperature emphasizes the role of excited states for detecting such exotic properties associated with otherwise hard-to-identify topological QSLs.Comment: 5 pages, 3 figure