ZNF577 Methylation Levels in Leukocytes From Women With Breast Cancer Is Modulated by Adiposity, Menopausal State, and the Mediterranean Diet

The methylation levels of ZNF577 in breast tumors has been previously identified as a possible epigenetic mark of breast cancer associated with obesity. The aim of the current study was to investigate differences in methylation levels of ZNF577 depending on obesity, menopausal state and dietary pattern in blood leukocytes, a non-invasive sample. The methylation levels of ZNF577 of two CpG sites (CpGs) located in promoter and island previously identified as differentially methylated according to adiposity and menopausal state by 450 k array (cg10635122, cg03562414) were evaluated by pyrosequencing in DNA from the blood leukocytes of breast cancer patients [n = 90; n = 64 (71.1%) overweight/obesity and n = 26 (28.9%) normal-weight] and paired tumor tissue biopsies (n = 8 breast cancer patients with obesity; n = 3/5 premenopausal/postmenopausal women). Differences in methylation levels were evaluated at each CpGs individually and at the mean of the two evaluated CpGs. Adherence to the Mediterranean diet was evaluated using the MEDAS-validated questionnaire, and the consumption of food groups of interest was also evaluated using the recommended intakes of the Sociedad Espanola de Nutricion Comunitaria. The methylation levels of ZNF577 were correlated between paired leukocytes and breast tumor biopsies (r = 0.62; p = 0.001). Moreover, higher methylation was found in leukocytes from patients with obesity (p = 0.002) and postmenopausal patients (p = 0.022) than patients with normal-weight or premenopausal, respectively. After adjusting for the body mass index and age, higher levels of ZNF577 methylation were also found in women with greater adherence to the Mediterranean diet (p = 0.017) or specific foods. Relevantly, the methylation levels of ZNF577 showed a good ability for fish consumption detection [area under the ROC curve (AUC) = 0.72; p = 0.016]. In conclusion, the association between methylation of ZNF577 and adiposity, menopausal state, and adherence to the Mediterranean diet can be detected in the blood leukocytes. The results guarantee the need of performing further studies in longer longitudinal cohorts in order to elucidate the role of ZNF577 methylation in the association between breast cancer, adiposity and dietary patterns

CTCs expression profiling for advanced breast cancer monitoring

The study of circulating tumor cells (CTCs) has a huge clinical interest in advance and metastatic breast cancer patients. However, many approaches are biased by the use of epithelial markers, which underestimate non-epithelial CTCs phenotypes. CTCs enumeration provides valuable prognostic information; however, molecular characterization could be the best option to monitor patients throughout the disease since it may provide more relevant clinical information to the physicians. In this work, we aimed at enumerating and performing a molecular characterization of CTCs from a cohort of 20 patients with metastatic breast cancer (MBC), monitoring the disease at different time points of the therapy, and at progression when it occurred. To this end, we used a CTC negative enrichment protocol that allowed us to recover a higher variety of CTCs phenotypes. With this strategy, we were able to obtain gene expression data from CTCs from all the patients. In addition, we found that high expression levels of PALB2 and MYC were associated with a worse outcome. Interestingly, we identified that CTCs with an EpCAM(high)VIM(low)ALDH1A1(high) signature showed both shorter overall survival (OS) and progression-free survival (PFS), suggesting that CTCs with epithelial-stem features had the most aggressive phenotype

On the Mechanism of the Copper-Catalyzed Enantioselective 1,4-Addition of Grignard Reagents to α,β-Unsaturated Carbonyl Compounds

The mechanism of the enantioselective 1,4-addition of Grignard reagents to α,β-unsaturated carbonyl compounds promoted by copper complexes of chiral ferrocenyl diphosphines is explored through kinetic, spectroscopic, and electrochemical analysis. On the basis of these studies, a structure of the active catalyst is proposed. The roles of the solvent, copper halide, and the Grignard reagent have been examined. Kinetic studies support a reductive elimination as the rate-limiting step in which the chiral catalyst, the substrate, and the Grignard reagent are involved. The thermodynamic activation parameters were determined from the temperature dependence of the reaction rate. The putative active species and the catalytic cycle of the reaction are discussed.

Chiral bosonization for non-commutative fields

A model of chiral bosons on a non-commutative field space is constructed and new generalized bosonization (fermionization) rules for these fields are given. The conformal structure of the theory is characterized by a level of the Kac-Moody algebra equal to $(1+ \theta^2)$ where $\theta$ is the non-commutativity parameter and chiral bosons living in a non-commutative fields space are described by a rational conformal field theory with the central charge of the Virasoro algebra equal to 1. The non-commutative chiral bosons are shown to correspond to a free fermion moving with a speed equal to $c^{\prime} = c \sqrt{1+\theta^2}$ where $c$ is the speed of light. Lorentz invariance remains intact if $c$ is rescaled by $c \to c^{\prime}$. The dispersion relation for bosons and fermions, in this case, is given by $\omega = c^{\prime} | k|$.Comment: 16 pages, JHEP style, version published in JHE

Wage inequality, segregation by skill and the price of capital in an assignment model

Some pieces of empirical evidence suggest that in the U.S., over the last few decades, (i) wage inequality between-plants has risen much more than wage inequality within-plants and (ii) there has been an increase in the segregation of workers by skill into separate plants. This paper presents a frictionless assignment model in which these two features can be explained simultaneously as the result of the decline in the relative price of capital. Additional implications of the model regarding the skill premium and the dispersion in labor productivity across plants are also consistent with the empirical evidence. [resumen de autor

The labor market effects of technology shocks

We analyze the effects of neutral and investment-specific technology shocks on hours worked and unemployment. We characterize the response of unemployment in terms of job separation and job finding rates. We find that job separation rates mainly account for the impact response of unemployment while job finding rates for movements along its adjustment path. Neutral shocks increase unemployment and explain a substantial portion of unemployment and output volatilityinvestment-specific shocks expand employment and hours worked and mostly contribute to hours worked volatility. We show that this evidence is consistent with the view that neutral technological progress prompts Schumpeterian creative destruction, while investment specific technological progress has standard neoclassical feature