Suchergebnisse

The population of Portoviejo and Guayaquil responded massively to the social crisis that broke out in Ecuador in mid-1959. Resorting to Martial Law, the administration of the Christian-Socialist Camilo Ponce opted for repression with the order to "shoot to kill", which resulted in hundreds dead. Since then, all levels of political power have attempted to dissipate the social memory of these events by silencing them. On the other hand, academia has addressed these events only in passing. Through the study of press articles of the period, as well as of official documents, the paper attempts to unravel the political and cultural web that has encouraged the inhibition of memory. It shows that the government repression, with its tragic toll, was legitimized on the basis of a political myth regarding a new "Bogotazo" and of a discourse that threatened the very existence of Guayaquil, both of which were widely disseminated by the media. Besides contributing to the historiography on Ecuador, the article seeks to foster the activation of a politics of memory. ; La crisis social que se manifestó en Ecuador a mediados de 1959 tuvo una respuesta masiva por parte de la población de Portoviejo y Guayaquil. Al amparo de la Ley Marcial, el gobierno del socialcristiano Camilo Ponce dispuso de la represión, con la consigna "tirar a matar", dejando como resultado centenares de fallecidos. Desde todas las instancias del poder político se ha intentado disipar la memoria social sobre esos hechos mediante su silenciamiento. La academia, por su lado, ha abordado estos hechos de manera fugaz. Este trabajo pretende descifrar la trama política y cultural que ha propiciado la inhibición de la memoria, mediante el examen de artículos de la prensa de la época y documentos oficiales. Se muestra así que la decisión gubernamental de la represión, con su saldo trágico, fue eficazmente legitimada a partir de un mito político sobre un nuevo "bogotazo", y de un discurso de amenaza a la existencia misma de Guayaquil, que fueron presentados por muchos medios de comunicación. Además del aporte a la historiografía sobre Ecuador, el escrito se propone contribuir con la activación de una política de memoria.

Yong-hong Pan, Lin Jiao, Cai-yu Lin, Cong-hua Lu, Li Li, Heng-yi Chen, Yu-bo Wang, Yong He Department of Respiratory Disease, Daping Hospital, Third Military Medical University, Chongqing 400042, China Aim: Although EGFR tyrosine kinase inhibitors (TKIs) have shown dramatic effects against sensitizing EGFR mutations in non-small cell lung cancer (NSCLC), ~20%–30% of NSCLC patients with EGFR-sensitive mutation exhibit intrinsic resistance to EGFR-TKIs. The purpose of the current study was to investigate the enhanced antitumor effect of metformin (Met), a biguanide drug, in combination with gefitinib (Gef) in primary resistant human lung cancer cells and the associated molecular mechanism.Experimental design: H1975 cell line was treated with Met and/or Gef to examine the inhibition of cell growth and potential mechanism of action by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Ki67 incorporation assay, flow cytometry analysis, small interfering RNA technology, Western blot analysis and xenograft implantation.Results: Insulin-like growth factor-1 receptor (IGF-1R) signaling pathway was markedly activated in EGFR-TKI primary resistant H1975 cells as compared to EGFR-TKI acquired resistance cells (PC-9GR, H1650-M3) and EGFR-TKI sensitivity cells (PC-9, HCC827). Inhibition of IGF-1R activity by AG-1024 (a small molecule of IGF-1R inhibitor), as well as downregulation of IGF-1R by siRNA, significantly enhanced the ability of Gef to suppress proliferation and induce apoptosis in H1975 cells via the inhibition of AKT activation and subsequent upregulation of Bcl-2-interacting mediator of cell death (BIM). Interestingly, the observation showed that Met combined with Gef treatment had similar tumor growth suppression effects in comparison with the addition of AG-1024 to therapy with Gef. A clear synergistic antiproliferative interaction between Met and Gef was observed with a combination index (CI) value of 0.65. Notably, IGF-1R silencing mediated by RNA interference (RNAi) attenuated anticancer effects of Met without obviously resensitizing H1975 cells to Gef. Finally, Met-based combinatorial therapy effectively blocked tumor growth in the xenograft with TKI primary resistant lung cancer cells.Conclusion: Our findings demonstrated that Met combined with Gef would be a promising strategy to overcome EGFR-TKI primary resistance via suppressing IGF-1R signaling pathway in NSCLC. Keywords: metformin, gefitinib, IGF-1R, primary resistance, lung cancer

У статті розглянуто сутність, основні складові економічної безпеки держави та її найважливіші структурні елементи. Висвітлено роль інституціонального інвестиційного середовища в межах здійснення економічної взаємодії між суб'єктами процесів інвестування. Зазначені ключові проблеми інституціонального інвестиційного середовища, яке тісно пов'язане із становленням економічної безпеки. Виявлено негативний вплив на інвестиційне інституціональне середовище за рахунок високого рівня адміністративних бар'єрів та у яких випадках вони себе проявляють. Розглянуті шляхи вдосконалення механізмів захисту прав власності. Наведено негативні наслідки наявності адміністративних бар'єрів для інвесторів та запропоновано комплекс заходів, санкціоновані державою, щодо їх усунення. Зазначено низку умов, щодо активізації участі держави в інвестиційних процесах в Україні. Надано пропозиції щодо формування інституційного регулювання інвестиційної діяльності в аграрний сектор економіки України. ; The article considers the essence, the main components of the economic security of the state and its most important structural elements. The role of the institutional investment environment within the framework of realization of economic interaction between the subjects of investment processes is highlighted. The asymmetry of the market information of the state and how it manifests itself is considered. The key problems of the institutionally Investment environment are identified, which is closely linked with the formation of economic security. The link between investments in the agrarian sector and components of economic security of the country is determined. The negative influence on the investment institutional environment due to the high level of administrative barriers and in which cases they manifest themselves. The ways of improvement of mechanisms of protection of property rights are considered. The negative consequences of the existence of administrative barriers for investors are presented and a set of measures authorized by the state for eliminating them is proposed. There are a number of conditions regarding the activation of state participation in investment processes in Ukraine. Proposals are made on the formation of institutional regulation of Investment activities in the agricultural sector of Ukraine. The function of providing public goods, which is realized by the state, is considered, and causes differences in the government's adoption of economic decisions, investment projects in comparison with other participants in investment processes. The expediency of differentiating the interests of the state and interests of other subjects of investment processes is considered.

Background: Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with a complex genetic inheritance. Genome-wide association studies (GWAS) have significantly increased the number of significant loci associated with SLE risk. To date, however, established loci account for less than 30% of the disease heritability and additional risk variants have yet to be identified. Here we performed a GWAS followed by a meta-analysis to identify new genome-wide significant loci for SLE. Methods: We genotyped a cohort of 907 patients with SLE (cases) and 1524 healthy controls from Spain and performed imputation using the 1000 Genomes reference data. We tested for association using logistic regression with correction for the principal components of variation. Meta-analysis of the association results was subsequently performed on 7,110,321 variants using genetic data from a large cohort of 4036 patients with SLE and 6959 controls of Northern European ancestry. Genetic association was also tested at the pathway level after removing the effect of known risk loci using PASCAL software. Results: We identified five new loci associated with SLE at the genome-wide level of significance (p < 5 × 10? 8): GRB2, SMYD3, ST8SIA4, LAT2 and ARHGAP27. Pathway analysis revealed several biological processes significantly associated with SLE risk: B cell receptor signaling (p = 5.28 × 10? 6), CTLA4 co-stimulation during T cell activation (p = 3.06 × 10? 5), interleukin-4 signaling (p = 3.97 × 10? 5) and cell surface interactions at the vascular wall (p = 4.63 × 10? 5). Conclusions: Our results identify five novel loci for SLE susceptibility, and biologic pathways associated via multiple low-effect-size loci. ; This study was funded by the Spanish Ministry of Economy and Competitiveness (grant numbers: PSE-010000-2006-6 and IPT-010000-2010-36). This work has been also sponsored by the grant SEV-2011-00067 of Severo Ochoa Program, awarded by the Spanish Government. This work was supported by an EFSD/Lilly research fellowship. Josep M. Mercader was supported by Sara Borrell Fellowship from the Instituto Carlos III. Sílvia Bonàs was awarded an FI-DGR Fellowship from FI-DGR 2013 from Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR, Generalitat de Catalunya). The study sponsors had no role in the design of the study, collection, analysis or interpretation of the data.

Long INterspersed Element class 1 (LINE-1) elements are a type of abundant retrotransposons active in mammalian genomes. An average human genome contains ~100 retrotransposition-competent LINE-1s, whose activity is influenced by the combined action of cellular repressors and activators. TREX1, SAMHD1 and ADAR1 are known LINE-1 repressors and when mutated cause the autoinflammatory disorder Aicardi-Goutières syndrome (AGS). Mutations in RNase H2 are the most common cause of AGS, and its activity was proposed to similarly control LINE-1 retrotransposition. It has therefore been suggested that increased LINE-1 activity may be the cause of aberrant innate immune activation in AGS. Here, we establish that, contrary to expectations, RNase H2 is required for efficient LINE-1 retrotransposition. As RNase H1 overexpression partially rescues the defect in RNase H2 null cells, we propose a model in which RNase H2 degrades the LINE-1 RNA after reverse transcription, allowing retrotransposition to be completed. This also explains how LINE-1 elements can retrotranspose efficiently without their own RNase H activity. Our findings appear to be at odds with LINE-1-derived nucleic acids driving autoinflammation in AGS. ; M.B.-G. is funded by a "Formacion Profesorado Universitario" (FPU) PhD fellowship from the Government of Spain (MINECO, Ref FPU15/03294), and this paper is part of her thesis project ("Epigenetic control of the mobility of a human retrotransposon"). R.V.-A. is funded by a PFIS Fellowship from the Government of Spain (ISCiii, FI16/00413). O.M. is funded by an EMBO Long-Term Fellowship (ALTF 7-2015), the European Commission FP7 (Marie Curie Actions, LTFCOFUND2013, GA-2013-609409) and the Swiss National Science Foundation (P2ZHP3_158709). S.R.H. is funded by the Government of Spain (MINECO, RYC-2016-21395 and SAF2015-71589-P). A.P.J's laboratory is supported by the UK Medical Research Council (MRC University Unit grant U127527202). J.L.G.P's laboratory is supported by CICEFEDER- P12-CTS-2256, Plan Nacional de I+D+I 2008-2011 and 2013-2016 (FISFEDER- PI14/02152), PCIN-2014-115-ERA-NET NEURON II, the European Research Council (ERC-Consolidator ERC-STG-2012-233764), by an International Early Career Scientist grant from the Howard Hughes Medical Institute (IECS-55007420), by The Wellcome Trust-University of Edinburgh Institutional Strategic Support Fund (ISFF2) and by a private donation from Ms Francisca Serrano (Trading y Bolsa para Torpes, Granada, Spain).

This is the final version of the article. Available from Mary Ann Liebert via the DOI in this record. ; City-regions as sites of sustainability transitions have remained under-explored so far. With our comparative analysis of five diverse European city-regions, we offer new insights on contemporary sustainability transitions at the urban level. In a similar vein, the pre-development and the take-off phase of sustainability transitions have been studied in depth while the acceleration phase remains a research gap. We address this research gap by exploring how transitions can move beyond the seeding of alternative experiments and the activation of civil society initiatives. This raises the question of what commonalities and differences can be found between urban sustainability transitions. In our explorative study, we employ a newly developed framework of the acceleration mechanisms of sustainability transitions. We offer new insights on the multi-phase model of sustainability transitions. Our findings illustrate that there are no clear demarcations between the phases of transitions. From the perspective of city-regions, we rather found dynamics of acceleration, deceleration, and stagnation to unfold in parallel. We observed several transitions—transitions towards both sustainability and un-sustainability—to co-evolve. This suggests that the politics of persistence—the inertia and path dependencies of un-sustainability—should be considered in the study of urban sustainability transitions. ; The article is based on research carried out as part of the ARTS project (Accelerating and Rescaling Transitions to Sustainability) funded under the European Framework Programme for Research and Innovation under the grant agreement 603654. Although the authors take full responsibility for the paper, it is based on valuable contributions and comments from the whole ARTS consortia, including Andreas Blum, Kristin Reiß, Gordon MacKerron, Rachael Durrant, Erika Meynaerts, Magnus Tuvendal, My Svensdotter, Maria Schewenius, Nikolina Oreskovic, Giorgia Silvestri, Matthew Bach, Felix Spira, Derk Loorbach and Steffen Maschmeyer. We would also like to thank all of our respondents for giving up their valuable time to engage in interviews and workshops to make this research possible. We thank the anonymous reviewers for comments and constructive critique on an earlier version of this paper. The content of the paper does not necessarily reflect the opinion of the European Commission.

Attention maintenance is highly demanding and typically leads to vigilance decrement along time on task. Therefore, performance in tasks involving vigilance maintenance for long periods, such as driving, tends to deteriorate over time. Cognitive performance has been demonstrated to fluctuate over 24 h of the day (known as circadian oscillations), thus showing peaks and troughs depending on the time of day (leading to optimal and suboptimal times of day, respectively). Consequently, vigilance decrements are more pronounced along time on task when it is performed at suboptimal times of day. According to research, light exposure (especially blue-enriched white) enhances alertness. Thus, it has been proposed to prevent the vigilance decrement under such adverse circumstances. We aimed to explore the effects of blue-enriched white light (vs. dim light) on the performance of a simulated driving task at a suboptimal time of day. A group of evening-types was tested at 8 am, as this chronotype had previously shown their largest vigilance decrement at that time. In the dim light condition, vigilance decrements were expected on both subjective (as increments in the Karolinska Sleepiness Scale scores) and behavioral measures [as slower reaction times (RTs) in the auditory Psychomotor Vigilance Task, slower RTs to unexpected events during driving, and deteriorated driving accuracy along time on task]. Physiological activation was expected to decrease (as indexed by an increase of the distal-proximal temperature gradient, DPG). Under blue-enriched white light, all these trends should be attenuated. Results from the control dim light condition replicated the vigilance decrement in all measures. Most important, the blue-enriched white light attenuated this decrement, leading to both lower DPG and faster RTs. However, it impaired accuracy of driving performance, and did not have any effect on subjective sleepiness. We conclude that exposure to blue-enriched light provides an effective countermeasure to enhance vigilance performance at suboptimal times of day, according to measures such as RTs. However, it should be considered that alerting effects of light could impair accuracy in precision tasks as keeping a proper car position. The current findings provide ergonomic implications for safety and fatigue related management systems. ; This work was supported by the Spanish and Andalusian Governments to ÁC (MINECO: PSI2014-58041-P, and Proyectos de Excelencia JJAA: SEJ-3054) and to JM (MINECO: SAF2013- 49132-C2-1-R).

The electroencephalogram (EEG) constitutes a relevant tool to study neural dynamics and to develop brain-machine interfaces (BMI) for rehabilitation of patients with paralysis due to stroke. However, the EEG is easily contaminated by artifacts of physiological origin, which can pollute the measured cortical activity and bias the interpretations of such data. This is especially relevant when recording EEG of stroke patients while they try to move their paretic limbs, since they generate more artifacts due to compensatory activity. In this paper, we study how physiological artifacts (i.e., eye movements, motion artifacts, muscle artifacts and compensatory movements with the other limb) can affect EEG activity of stroke patients. Data from 31 severely paralyzed stroke patients performing/attempting grasping movements with their healthy/paralyzed hand were analyzed offline. We estimated the cortical activation as the event-related desynchronization (ERD) of sensorimotor rhythms and used it to detect the movements with a pseudo-online simulated BMI. Automated state-of-the-art methods (linear regression to remove ocular contaminations and statistical thresholding to reject the other types of artifacts) were used to minimize the influence of artifacts. The effect of artifact reduction was quantified in terms of ERD and BMI performance. The results reveal a significant contamination affecting the EEG, being involuntary muscle activity the main source of artifacts. Artifact reduction helped extracting the oscillatory signatures of motor tasks, isolating relevant information from noise and revealing a more prominent ERD activity. Lower BMI performances were obtained when artifacts were eliminated from the training datasets. This suggests that artifacts produce an optimistic bias that improves theoretical accuracy but may result in a poor link between task-related oscillatory activity and BMI peripheral feedback. With a clinically relevant dataset of stroke patients, we evidence the need of appropriate methodologies to remove artifacts from EEG datasets to obtain accurate estimations of the motor brain activity. ; This study was funded by the fortüne-Program of the University of Tübingen (2422-0-1 and 2452-0-0), the Bundesministerium für Bildung und Forschung BMBF MOTORBIC (FKZ 13GW0053) and AMORSA (FKZ 16SV7754), the Deutsche Forschungsgemeinschaft (DFG), the Basque Government Science Program (EXOTEK: KK 2016/00083). The work of A. Insausti-Delgado was supported by the Basque Government's scholarship for predoctoral students.

18 páginas, 8 figuras, 1 tabla ; PII, a homotrimeric very ancient and highly widespread (bacteria, archaea, plants) key sensor-transducer protein, conveys signals of abundance or poorness of carbon, energy and usable nitrogen, converting these signals into changes in the activities of channels, enzymes, or of gene expression. PII sensing is mediated by the PII allosteric effectors ATP, ADP (and, in some organisms, AMP), 2-oxoglutarate (2OG; it reflects carbon abundance and nitrogen scarcity) and, in many plants, L-glutamine. Cyanobacteria have been crucial for clarification of the structural bases of PII function and regulation. They are the subject of this review because the information gathered on them provides an overall structure-based view of a PII regulatory network. Studies on these organisms yielded a first structure of a PII complex with an enzyme, (N-acetyl-Lglutamate kinase, NAGK), deciphering how PII can cause enzyme activation, and how it promotes nitrogen stockpiling as arginine in cyanobacteria and plants. They have also revealed the first clear-cut mechanism by which PII can control gene expression. A small adaptor protein, PipX, is sequestered by PII when nitrogen is abundant and is released when is scarce, swapping partner by binding to the 2OG-activated transcriptional regulator NtcA, co-activating it. The structures of PII-NAGK, PII-PipX, PipX alone, of NtcA in inactive and 2OG-activated forms and as NtcA-2OG-PipX complex, explain structurally PII regulatory functions and reveal the changing shapes and interactions of the T-loops of PII depending on the partner and on the allosteric effectors bound to PII. Cyanobacterial studies have also revealed that in the PII-PipX complex PipX binds an additional transcriptional factor, PlmA, thus possibly expanding PipX roles beyond NtcA-dependency. Further exploration of these roles has revealed a functional interaction of PipX with PipY, a pyridoxal-phosphate (PLP) protein involved in PLP homeostasis whose mutations in the human ortholog cause epilepsy. Knowledge of cellular levels of the different components of this PII-PipX regulatory network and of KD values for some of the complexes provides the basic background for gross modeling of the system at high and low nitrogen abundance. The cyanobacterial network can guide searches for analogous components in other organisms, particularly of PipX functional analogs. ; Supported by grants BFU2014-58229-P and BFU2017-84264-P from the Spanish Government. ; Peer reviewed

The article analyzes the idea of tolerance of students in the national educational thought of the second half of the XX-XXI centuries and sets periods of its development. Overall 3 periods are allocated: The first period (50-80s of the twentieth century) – development of the idea of tolerance within the international education of the Soviet period. International education was one of the main directions of the ideological work of the pupils and one of the important parts of Soviet pedagogy, while its components were very controversial. The second period (90s of the twentieth century) – the development of tolerance in the process of humanization and democratization of the educational process. Scientists of the 90s considered that the core qualities of the individual were spirituality, national identity, citizenship, creativity. At this time, the formation of a new paradigm of education begins, which vectors can be considered universal values (spirituality) and national values (national identity, citizenship). It is among these universal values and national the prominent place belongs to tolerance. The third period (beginning of the XXI century – Present day) – activation of the implementation of ideas of tolerance in the training and education of youth, the restructuring of the educational policy of Ukraine in view of European integration processes. Pedagogical research of the XXI century suggest that one of the areas where most needed of forming attitudes and norms of tolerant behavior is the education system that fosters education responsive and responsible citizens open to accept other cultures, able to appreciate the freedom, respect for human dignity and individuality. Appeals to the modern scientific papers show that by examining the process of tolerance, researchers focus on its particular species (international, ethnic, etc.) or in a certain age category of students. ; У статті подано результати аналізу розвитку ідеї толерантностіучнівської молоді у вітчизняній педагогічній думці ІІ половини ХХ –початку ХХІ ст. та встановлено періоди її розвитку. Обґрунтовановиділення 3 періодів: І період (50-80-ті роки ХХ ст.) – розвиток ідеї толерантності в рамках інтернаціонального виховання радянського періоду;ІІ період (90-ті роки ХХ ст.) – розвиток толерантності в процесі гуманізаціїй демократизації освітньо-виховного процесу; ІІІ період (початок ХХІ ст. –донині) – активізація впровадження ідей толерантності в процес навчання тавиховання учнівської молоді, перебудова освітньої політики України зурахуванням євроінтеграційних процесів.

Рассматривается одна из современных форм организационных преобразований в системе высшего профессионального образования — сетевое взаимодействие вузов. Авторами подчеркивается важность сетевого взаимодействия в сфере высшего образования и подготовки научных кадров как формы региональной интеграции. Проанализирована практика сетевого взаимодействия Алтайского государственного университета. Приведены примеры эффективных форм сотрудничества вузов в современном мире. Сетевое взаимодействие университетов в современной высококонкурентной среде позволяет консолидировать возможности развития университетов различных стран, многократно увеличивать тем самым ресурсы интеллекта, кадров, инфраструктуры — сформировать масштабный базис для нового рывка в области знаний и технологий. На примерах создания международных организаций и участия в них, проведения международных форумов отмечены наиболее эффективные формы и виды образовательного сотрудничества. Результаты совместной деятельности, которые получены благодаря сотрудничеству азиатских университетов в рамках Ассоциации азиатских университетов, позволяют уверенно вписаться в процессы активизации политико-экономических интеграционных процессов в регионе, которую мы наблюдаем в последние годы, в том числе в рамках международных объединений (СНГ, ЕАЭС, ШОС, БРИКС). DOI 10.14258/izvasu(2016)4-35 ; The article considers one of the modern forms of organizational transformations in the system of higher professional education, which is a network cooperation of higher educational institutions. The authors emphasize the importance of network cooperation in the sphere of higher education and training of scientific specialists as a form of regional integration. The authors have analyzed Altai State University's experience of network cooperation and provided the examples of effective forms of higher educational institutions' cooperation in the modern world. Universities network cooperation under modern highly competitive conditions allows consolidating development opportunities for universities of different countries, thus repeatedly increasing intellectual resources, personnel resources, resources of infrastructure, thereby to form a large-scale basis for a new breakthrough in the field of knowledge and technology. On the example of creation and participation in international organizations, hosting of international forums there were distinguished the most effective forms and types of educational cooperation. The results of joint activities which were obtained with the help of cooperation of the universities in the framework of the Association make it possible to fit into political and economic integrational activation processes, which we have been obser ving during the recent years within the framework of international associations (CIS, EAEC, SCO, BRICS). DOI 10.14258/izvasu(2016)4-35

El escenario de la participación política en Colombia es uno de los ámbitos en que más se evidencia la discriminación de las mujeres, diversos estudios desde distintas ramas de la psicología han mostrado que las atribuciones que se realizan sobre el desempeño de una persona están marcadas por los estereotipos y no obedecen totalmente a la realidad. La relación entre baja participación política y estereotipos puede ser explicada por el efecto de amenaza de estereotipo, en el cual el miedo a caer en los estereotipos y reafirmarlos puede opacar la motivación de las mujeres a ocupar cargos de liderazgo social en el ámbito público. Se realizó un estudio experimental- exploratorio sobre dicho efecto con 284 estudiantes de grado noveno y décimo matriculados en tres colegios públicos de la ciudad de Bogotá. Los resultados muestran que la activación de estereotipos de género relacionados con el liderazgo femenino aumenta la medida de estereotipos en el grupo experimental, siendo más alta para las mujeres, lo que en consecuencia disminuye la motivación al liderazgo para ellas. Se discuten los hallazgos a la luz de las implicaciones que tiene para las mujeres vivir en una sociedad en que los estereotipos de género están naturalizados y se aprenden muy temprano en el curso del desarrollo. ; Abstract. The scenario of political participation in Colombia is one of the areas where discrimination against women is more evident, several studies from different fields of psychology have shown that the attributions made over performance of a person, are marked by the stereotypes and do not completely obey reality. Stereotype threat can explain the relationship between low political participation and stereotypes, in which case, the fear of falling into stereotypes and reaffirming them may hinder the motivation of women to hold positions of social leadership in the public domain. We carried out an experimental-exploratory study on this effect with 284 students of 9 and 10 grades enrolled in three public schools in Bogotá. The results show that the activation of gender stereotypes related to female leadership increases the stereotype measured in the experimental group, being higher for women, which consequently decreases leadership motivation for them. The findings and the implications for women living in a society with naturalized gender stereotypes that they learn very early during development are further discussed. ; Maestría

[Background] : The organisation of vertebrate genomes into topologically associating domains (TADs) is believed to facilitate the regulation of the genes located within them. A remaining question is whether TAD organisation is achieved through the interactions of the regulatory elements within them or if these interactions are favoured by the pre-existence of TADs. If the latter is true, the fusion of two independent TADs should result in the rewiring of the transcriptional landscape and the generation of ectopic contacts. ; [Results]: We show that interactions within the PAX3 and FOXO1 domains are restricted to their respective TADs in normal conditions, while in a patient-derived alveolar rhabdomyosarcoma cell line, harbouring the diagnostic t(2;13)(q35;q14) translocation that brings together the PAX3 and FOXO1 genes, the PAX3 promoter interacts ectopically with FOXO1 sequences. Using a combination of 4C-seq datasets, we have modelled the three-dimensional organisation of the fused landscape in alveolar rhabdomyosarcoma. ; [Conclusions]: The chromosomal translocation that leads to alveolar rhabdomyosarcoma development generates a novel TAD that is likely to favour ectopic PAX3:FOXO1 oncogene activation in non-PAX3 territories. Rhabdomyosarcomas may therefore arise from cells which do not normally express PAX3. The borders of this novel TAD correspond to the original 5'- and 3'- borders of the PAX3 and FOXO1 TADs, respectively, suggesting that TAD organisation precedes the formation of regulatory long-range interactions. Our results demonstrate that, upon translocation, novel regulatory landscapes are formed allowing new intra-TAD interactions between the original loci involved. ; This work was supported by The Institute of Cancer Research and Cancer Research UK (Grant C1178/A4520). JJC was funded by grants from Spanish Ministerio de Ciencia e Innovación (BFU2011-22928) and the European Commission (PCIG10-GA-2011-303904). JLGS was funded by grants from Spanish Ministerio de Economía y Competitividad (BFU2013-41322-P) and the Andalusian Government (BIO-396). DPD and IIA were funded by grants from the Spanish Ministerio de Economia y Competitividad () and from the Junta de Andalucia (C2A). BV-B held a studentship from The Institute of Cancer Research. ; We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI). ; Peer reviewed

Polo-like kinase 1 (PLK1), an essential regulator of cell division, is currently undergoing clinical evaluation as a target for cancer therapy. We report an unexpected function of Plk1 in sustaining cardiovascular homeostasis. Plk1 haploinsufficiency in mice did not induce obvious cell proliferation defects but did result in arterial structural alterations, which frequently led to aortic rupture and death. Specific ablation of Plk1 in vascular smooth muscle cells (VSMCs) led to reduced arterial elasticity, hypotension, and an impaired arterial response to angiotensin II in vivo. Mechanistically, we found that Plk1 regulated angiotensin II-dependent activation of RhoA and actomyosin dynamics in VSMCs in a mitosis-independent manner. This regulation depended on Plk1 kinase activity, and the administration of small-molecule Plk1 inhibitors to angiotensin II-treated mice led to reduced arterial fitness and an elevated risk of aneurysm and aortic rupture. We thus conclude that a partial reduction of Plk1 activity that does not block cell division can nevertheless impair aortic homeostasis. Our findings have potentially important implications for current approaches aimed at PLK1 inhibition for cancer therapy. ; This work-was supported by the Marie Curie activities of the European Commission (Oncotrain program; fellowship to P.W), the Spanish Ministry of Economy and Competitiveness (MINECO; fellowship to A.G.-L.), the CENIT AMIT Project "Advanced Molecular Imaging Technologies" (TEC2008-06715-C02-1, RD07/0014/2009 to F.M.), the Red de investigacion Cardiovascular (RIC), cofunded by FEDER (grant RD12/004240022 to J.M.R.; grant RD12/0042/0056 to L.J.J.-B), Fundacio La Marato TV3 (grant 20151331 to J.M.R.), the Castilla-Leon Autonomous Government (BIO/SA01/15, CS049U16 to X.R.B.), the Solorzano and Ramon Areces Foundations (to X.R.B.), MINECO (grants RD12/0036/0002 and SAF2015-64556-R to X.R.B.; SAF2015-63633-R to J.M.R.; and SAF2015-69920-R to M.M.), Consolider-Ingenio 2010 Programme (grant SAF2014-57791-REDC to M.M.), Red Tematica CellSYS (grant BFU2014-52125-REDT to M.M.), Comunidad de Madrid (OncoCycle Programme; grant S2010/BMD-2470 to M.M.), Worldwide Cancer Research (grants 14-1248 to X.R.B., and 15-0278 to M.M.) and the MitoSys project (European Union Seventh Framework Programme; grant HEALTH-F5-2010-241548 to M.M.). CNIC is supported by MINECO and the Pro-CNIC Foundation. CNIO and CNIC are Severo Ochoa Centers of Excellence (MINECO awards SEV-2015-0510 and SEV-2015-0505, respectively). ; Sí

The authors acknowledge the CPU time allocation at Academic Computer Centre CYFRONET AGH in Cracow. This work was supported in part by PL-Grid Infrastructure and the European Regional Development Fund under the Infrastructure and Environment Programme [grant number UDA-POIS.13.01-023/09-00]. The research was partially carried out with the equipment purchased thanks to the financial support of the European Regional Development Fund in the framework of the Polish Innovation Economy Operational Program (contract no. POIG.02.01.00-12-023/08). L. Vasylechko acknowledges partial support of the Ukrainian Ministry of Education and Sciences under the Projects ?RZE?, ?KMON?, and ICDD Grant-in-Aid program. The authors acknowledge Marek Kubik and Tomasz Prociak (from the Stanmark company, Cracow, Poland) for making available DMA measurements. The authors thank A. Fitch and Yu. Prots for kindly assistance with high-resolution synchrotron powder diffraction measurements at ID22 of ESRF during the beamtime allocated to the Experiment MA-2320 and Prof. Stanislaw Baran (Institute of Physics, Jagiellonian University, Cracow, Poland) for a fruitful discussion. ; Ceramic samples, produced by conventional sintering method in ambient air, 6H-SrMnO3 (6H-SMO), 15R-BaMnO3 (15R-BMO), 4H-Ba0.5Sr0.5MnO3 (4H-BSMO) were studied. In the XRD measurements for SMO the new anomalies of the lattice parameters at 600–800 K range and the increasing of thermal expansion coefficients with a clear maximum in a vicinity at 670 K were detected. The Ne´el phase transition for BSMO was observed at TN = 250 K in magnetic measurements and its trace was detected in dielectric, FTIR, DSC, and DMA experiments. The enthalpy and entropy changes of the phase transition for BSMO at TN were determined as 17.5 J/mol and 70 mJ/K mol, respectively. The activation energy values and relaxation times characteristic for relaxation processes were determined from the Arrhenius law. Results of ab initio simulations showed that the contribution of the exchange correlation energy to the total energy is about 30%. ; International Centre for Diffraction Data MA-2320 ICDD; European Regional Development Fund UDA-POIS.13.01-023/09-00,POIG.02.01.00-12-023/08; Institute of Solid State Physics, University of Latvia as the Center of Excellence has received funding from the European Union's Horizon 2020 Framework Programme H2020-WIDESPREAD-01-2016-2017-TeamingPhase2 under grant agreement No. 739508, project CAMART²