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Wireless phones (both mobile and cordless) emit not only radiofrequency (RF) electromagnetic fields (EMF) but also extremely low frequency (ELF) magnetic fields, both of which should be considered in epidemiological studies of the possible adverse health effects of use of such devices. This paper describes a unique algorithm, developed for the multinational case-control MOBI-Kids study, that estimates the cumulative specific energy (CSE) and the cumulative induced current density (CICD) in the brain from RF and ELF fields, respectively, for each subject in the study (aged 10–24 years old). Factors such as age, tumour location, self-reported phone models and usage patterns (laterality, call frequency/duration and hands-free use) were considered, as was the prevalence of different communication systems over time.Median CSE and CICD were substantially higher in GSM than 3G systems and varied considerably with location in the brain. Agreement between RF CSE and mobile phone use variables was moderate to null, depending on the communication system. Agreement between mobile phone use variables and ELF CICD was higher overall but also strongly dependent on communication system. Despite ELF dose distribution across the brain being more diffuse than that of RF, high correlation was observed between RF and ELF dose.The algorithm was used to systematically estimate the localised RF and ELF doses in the brain from wireless phones, which were found to be strongly dependent on location and communication system. Analysis of cartographies showed high correlation across phone models and across ages, however diagonal agreement between these cartographies suggest these factors do affect dose distribution to some level. Overall, duration and number of calls may not be adequate proxies of dose, particularly as communication systems available for voice calls tend to become more complex with time.

Regulation of histone acetylation dictates patterns of gene expression and hence cell identity. Due to their clinical relevance in cancer biology, understanding how human embryonic stem cells (hESCs) regulate their genomic patterns of histone acetylation is critical, but it remains largely to be investigated. Here, we provide evidence that acetylation of histone H3 lysine-18 (H3K18ac) and lysine-27 (H3K27ac) is only partially established by p300 in stem cells, while it represents the main histone acetyltransferase (HAT) for these marks in somatic cells. Our analysis reveals that whereas p300 marginally associated with H3K18ac and H3K27ac in hESCs, it largely overlapped with these histone marks upon differentiation. Interestingly, we show that H3K18ac is found at “stemness” genes enriched in RNA polymerase III transcription factor C (TFIIIC) in hESCs, whilst lacking p300. Moreover, TFIIIC was also found in the vicinity of genes involved in neuronal biology, although devoid of H3K18ac. Our data suggest a more complex pattern of HATs responsible for histone acetylations in hESCs than previously considered, suggesting a putative role for H3K18ac and TFIIIC in regulating “stemness” genes as well as genes associated with neuronal differentiation of hESCs. The results break ground for possible new paradigms for genome acetylation in hESCs that could lead to new avenues for therapeutic intervention in cancer and developmental diseases.

Ambos héroes, don Quijote y Sancho Panza, tienen la capacidad de narrarse a sí mismos, don Quijote en la Primera parte y Sancho en la Segunda, en Barataria, y bajo la potestad del duque. Como dice Grilli sobre el primer Quijote, «a grandes rasgos podemos describir las tres competencias de don Quijote “escribiente, orador y representante”», (2007, p. 40). Y yo afirmo lo mismo de Sancho, en el segundo Quijote. Detrás de la estructura de la Segunda parte, asoma su verdadero protagonista, Sancho, quien narra también su historia como buen escudero que ha conseguido su sueño, una experiencia, a la vez fantástica y terrible, la de ser gobernador de una ínsula, como le había prometido su amo. Y la escenifica y la representa en su gobierno según un recto principio basado en la virtud y en la sabiduría práctica. Y además de todo esto, resulta ser “un predicador” de la moral de Trento y del espíritu de la Contrarreforma, dejando al descubierto la inmoralidad y la corrupción de Barataria en el gobierno del señor duque. Sancho escribe también su propia novela porque don Quijote le cede la ilusión de la narratividad y protagonismo a Sancho, cuando él, como caballero y protagonista, ha perdido ya todos sus anhelos y perspectivas.

Transcription factors (TFs) bind DNA in a sequence-specific manner and are generally cell type-specific factors and/or developmental master regulators. In contrast, general TFs (GTFs) are part of very large protein complexes and serve for RNA polymerases’ recruitment to promoter sequences, generally in a cell type-independent manner. Whereas, several TFs have been proven to serve as anchors for the 3D genome organization, the role of GTFs in genome architecture have not been carefully explored. Here, we used ChIP-seq and Hi-C data to depict the role of TFIIIC, one of the RNA polymerase III GTFs, in 3D genome organization. We find that TFIIIC genome occupancy mainly occurs at specific regions, which largely correspond to Alu elements; other characteristic classes of repetitive elements (REs) such as MIR, FLAM-C and ALR/alpha are also found depending on the cell’s developmental origin. The analysis also shows that TFIIIC-enriched regions are involved in cell type-specific DNA looping, which does not depend on colocalization with the master architectural protein CTCF. This work extends previous knowledge on the role of TFIIIC as a bona fide genome organizer whose action participates in cell type-dependent 3D genome looping via binding to REs.

Radiotherapy (XRT) delivered with the antibody cetuximab is a standard treatment option for squamous cell carcinomas of head and neck (SCCNH). Cetuximab acts by blocking epidermal growth factor receptor (EGFR) signaling to inhibit cancer progression. However, a significant percentage of patients will not respond to XRT and cetuximab. Statins reduce the synthesis of cholesterol and isoprenoid derivates that may be required for efficient EGFR signaling. We assessed whether the statin simvastatin could improve this combined therapy. In vitro, simvastatin enhanced the effects of XRT alone and in combination with cetuximab in wound healing, cell proliferation, and clonogenic assays in FaDu cells. These results were reflected in xenoimplanted tumors growing into subcutaneous tissue of athymic mice where concomitant treatment with simvastatin decreased tumor growth. Consistently, lower levels of phosphorylated extracellular signal–regulated kinases 1 and 2, phosphatidylinositol 3-kinase/AKT–protein kinase B, and signal transducer and activator of transcription 3 oncoproteins and higher levels of caspase-3 and apoptosis in cell cultures and xenografts were observed. The EGFR-overexpressing A431 cell line was used to reproduce these antitumor effects of simvastatin. Our findings suggest that simvastatin may improve the efficiency of concomitant XRT and cetuximab. Further investigation in the treatment of SCCNH is warranted.

Con la traducción al catalán de Il Corbaccio por el mercader Narcís Franch (1498) se inicia una doble corriente peninsular de misoginia y feminismo. Sus argumentos pasaron a formar parte del pensamiento misógino defendido por el Arciprestre de Talavera, Bernat Metge, Jaume Roig, Francesc Eiximenis y Pere Torrelles. Sin embargo, esta tendencia de vituperio e invectiva contra las mujeres tuvo también sus detractores, lo que originó la llamada «querella de las mujeres» en defensa de sus valores. Hombres y mujeres como Christine de Pizan, Teresa de Cartagena, Isabel, Enrique de Villena y Rodríguez del Padrón atacaron la reprobación sistemática del sexo femenino, basándose en el De claris mulieribus de Boccaccio Partiendo de los argumentos pro y anti femeninos de La Fiammetta y Il Corbaccio se revisan textos y argumentos misóginos de la tradición, con el fin de elaborar una teoría sobre la «querelle de las mujeres» en la tradición catalana y castellana. The Catalan translation of II Corbaccio made by the merchant Narcís Franch (1948) initiates a double stream of though in the Spanish peninsula about misogyny and feminism. His arguments became part of the misogyny though defended by Arciprestre de Talavera, Bernat Metge, Jaume Roig, Francesc Eiximenis and Pere Torrelles. Nevertheless, this trend of though about disgrace and invective against women also had its detractors, which originated the socalled «querelle des femmes» in defense of their values. Men and women like Christine de Pizan, Teresa de Cartagena, Isabel, Enrique de Villena and Rodríguez del Padrón attacked the systematic condemnation of women, inspired by the Claris mulieribus of Boccaccio. Based on the arguments pro and against female of La Fiammetta and Il Corbaccio, this article will reviews other texts and misogynous arguments of the tradition, with the purpose of concluding my theory about the «querelle des femmes» in Catalonia and Castile.

Breast cancer prognosis and response to endocrine therapy strongly depends on the expression of the estrogen and progesterone receptors (ER and PR, respectively). Although much is known about ERα gene (ESR1) regulation after hormonal stimulation, how it is regulated in hormone-free condition is not fully understood. We used ER-/PR-positive breast cancer cells to investigate the role of PR in ESR1 regulation in the absence of hormones. We show that PR binds to the low-methylated ESR1 promoter and maintains both gene expression and DNA methylation of the ESR1 locus in hormone-deprived breast cancer cells. Depletion of PR reduces ESR1 expression, with a concomitant increase in gene promoter methylation. The high amount of methylation in the ESR1 promoter of PR-depleted cells persists after the stable re-expression of PR and inhibits PR binding to this genomic region. As a consequence, the rescue of PR expression in PR-depleted cells is insufficient to restore ESR1 expression. Consistently, DNA methylation impedes PR binding to consensus progesterone responsive elements. These findings contribute to understanding the complex crosstalk between PR and ER and suggest that the analysis of ESR1 promoter methylation in breast cancer cells can help to design more appropriate targeted therapies for breast cancer patients.

El trabajo constituye un estudio microhistórico sobre las difíciles circunstancias logísticas y políticas que acompañaron el proceso de constitución de una empresa de papel en Navarra en los inicios de la década de 1950. Su originalidad y su valor residen en que constituye una aportación personal basada en la consulta de archivos históricos familiares, por lo que no debe esperarse una contextualización histórica al uso.

Maria de Cazalla was condemned publicly by the Inquisition in the procceding of the 21th on April, 1529: She was condemned of "iluminist" and "lutheran", alter the Iluminist's Edict (Toledo, 23th on September, 1525). The influence of the book Doctrina cristiana, by Juan de Valdés, and the Erasmu's doctrine was imputed to her. She was accused of heretic practicing of inside devotion that shut out disciplines, fasting, verbal oartion, worship at images and gaze on the cross. She was also accused of dening the free-will and to be a preacher woman.

Abstract Background Radiation-induced DNA double-strand break (DSB) repair can be tested by using pulsed-field gel electrophoresis (PFGE) in agarose-encapsulated cells. However, previous studies have reported that this assay is impaired by the spontaneous DNA breakage in this medium. We investigated the mechanisms of this fragmentation with the principal aim of eliminating it in order to improve the estimation of radiation-induced DNA repair. Methods Samples from cancer cell cultures or xenografted tumours were encapsulated in agarose plugs. The cell plugs were then irradiated, incubated to allow them to repair, and evaluated by PFGE, caspase-3, and histone H2AX activation (γH2AX). In addition, apoptosis inhibition was evaluated through chemical caspase inhibitors. Results We confirmed that spontaneous DNA fragmentation was associated with the process of encapsulation, regardless of whether cells were irradiated or not. This DNA fragmentation was also correlated to apoptosis activation in a fraction of the cells encapsulated in agarose, while non-apoptotic cell fraction could rejoin DNA fragments as was measured by γH2AX decrease and PFGE data. We were able to eliminate interference of apoptosis by applying specific caspase inhibitors, and improve the estimation of DNA repair, and apoptosis itself. Conclusions The estimation of radiation-induced DNA repair by PFGE may be improved by the use of apoptosis inhibitors. The ability to simultaneously determine DNA repair and apoptosis, which are involved in cell fate, provides new insights for using the PFGE methodology as functional assay.

Potential differential and non-differential recall error in mobile phone use (MPU) in the multinational MOBI-Kids case-control study were evaluated. We compared self-reported MPU with network operator billing record data up to 3 months, 1 year, and 2 years before the interview date from 702 subjects aged between 10 and 24 years in eight countries. Spearman rank correlations, Kappa coefficients and geometric mean ratios (GMRs) were used. No material differences in MPU recall estimates between cases and controls were observed. The Spearman rank correlation coefficients between self-reported and recorded MPU in the most recent 3 months were 0.57 and 0.59 for call number and for call duration, respectively. The number of calls was on average underestimated by the participants (GMR = 0.69), while the duration of calls was overestimated (GMR = 1.59). Country, years since start of using a mobile phone, age at time of interview, and sex did not appear to influence recall accuracy for either call number or call duration. A trend in recall error was seen with level of self-reported MPU, with underestimation of use at lower levels and overestimation of use at higher levels for both number and duration of calls. Although both systematic and random errors in self-reported MPU among participants were observed, there was no evidence of differential recall error between cases and controls. Nonetheless, these sources of exposure measurement error warrant consideration in interpretation of the MOBI-Kids case-control study results on the association between children's use of mobile phones and potential brain cancer risk., (© 2024 The Author(s). Bioelectromagnetics published by Wiley Periodicals LLC on behalf of Bioelectromagnetics Society.)

Wireless phones (both mobile and cordless) emit not only radiofrequency (RF) electromagnetic fields (EMF) but also extremely low frequency (ELF) magnetic fields, both of which should be considered in epidemiological studies of the possible adverse health effects of use of such devices. This paper describes a unique algorithm, developed for the multinational case-control MOBI-Kids study, that estimates the cumulative specific energy (CSE) and the cumulative induced current density (CICD) in the brain from RF and ELF fields, respectively, for each subject in the study (aged 10-24 years old). Factors such as age, tumour location, self-reported phone models and usage patterns (laterality, call frequency/duration and hands-free use) were considered, as was the prevalence of different communication systems over time. Median CSE and CICD were substantially higher in GSM than 3G systems and varied considerably with location in the brain. Agreement between RF CSE and mobile phone use variables was moderate to null, depending on the communication system. Agreement between mobile phone use variables and ELF CICD was higher overall but also strongly dependent on communication system. Despite ELF dose distribution across the brain being more diffuse than that of RF, high correlation was observed between RF and ELF dose. The algorithm was used to systematically estimate the localised RF and ELF doses in the brain from wireless phones, which were found to be strongly dependent on location and communication system. Analysis of cartographies showed high correlation across phone models and across ages, however diagonal agreement between these cartographies suggest these factors do affect dose distribution to some level. Overall, duration and number of calls may not be adequate proxies of dose, particularly as communication systems available for voice calls tend to become more complex with time., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

Characterizing exposure to radiofrequency (RF) fields from wireless telecommunications technologies during childhood and adolescence is a research priority in investigating the health effects of RF. The Mobi-Expo study aimed to describe characteristics and determinants of cellular phone use in 534 young people (10-24years) in 12 countries. The study used a specifically designed software application installed on smartphones to collect data on the use of wireless telecommunications devices within this age group. The role of gender, age, maternal education, calendar period, and country was evaluated through multivariate models mutually adjusting for all variables. Call number and duration were higher among females compared to males (geometric mean (GM) ratio 1.17 and 1.42, respectively), among 20-24year olds compared to 10-14year olds (GM ratio 2.09 and 4.40, respectively), and among lowest compared to highest social classes (GM ratio 1.52 and 1.58, respectively). The number of SMS was higher in females (GM ratio 1.46) and the middle age group (15-19year olds: GM ratio 2.21 compared to 10-14year olds) and decreased over time. Data use was highest in the oldest age group, whereas Wi-Fi use was highest in the middle age group. Both data and Wi-Fi use increased over time. Large differences in the number and duration of calls, SMS, and data/Wi-Fi use were seen by country, with country and age accounting for up to 50% of the variance. Hands-free and laterality of use did not show significant differences by sex, age, education, study period, or country. Although limited by a convenience sample, these results provide valuable insights to the design, analysis, and interpretation of future epidemiological studies concerning the health effects of exposure resulting from cellular phone use in young people. In addition, the information provided by this research may be used to design strategies to minimize RF exposure., (Copyright © 2017 Elsevier Ltd. All rights reserved.)