Representation of defense organizations in the Marvel Cinematic Universe (2008-2019)

Homeland security and defense are common themes in superhero films. The Marvel Cinematic Universe (MCU) is formed by more than twenty films made over the course of a decade (2008-2019), during the government of three different Presidents of the United States. In this paper we analyze the diminishing representation of real defense forces in the MCU films. How the interference of the superhero is used as a narrative excuse to suggest a lack of or deficiencies in the law concerning freedom and defense is also studied, as well as how the films make a metaphorical discourse about the historical reality after September 11th

Novel and natural knockout lung cancer cell lines for the LKB1/STK11 tumor suppressor gene

Germline mutations of the LKB1 gene are responsible for Peutz-Jeghers syndrome (PJS), an autosomal dominant inherited disorder bestowing an increased risk of cancer. We have recently demonstrated that LKB1 inactivating mutations are not confined to PJS, but also appear in lung adenocarcinomas of sporadic origin, including primary tumors and lung cancer cell lines. To accurately determine the frequency of inactivating LKB1 gene mutations in lung tumors we have sequenced the complete coding region of LKB1 in 21 additional lung cancer cell lines. Here we describe the mutational status of LKB1 gene in 30 lung cancer cell lines from different histopathological types, including 11 lung adenocarcinomas (LADs) and 11 small cell lung cancers (SCLCs). LKB1 gene alterations were present in six (54%) of the LAD cell lines tested but in none of the other histological types. Similar to our previous observations in primary tumors, all point mutations were of the nonsense or frameshift type, leading to an abnormal, truncated protein. Moreover, 2 cell lines (A427 and H2126) harbored large gene deletions that spanned several exons. Hence, we have identified additional lung cancer cell lines carrying inactivating mutations of the LKB1 tumor suppressor gene, further attesting to the significance of this gene in the development of LADs and providing new natural LKB1 knockouts for studies of the biological function of the LKB1 protein

Genome-wide CRISPR interference screen identifies long non-coding RNA loci required for differentiation and pluripotency

Although many long non-coding RNAs (lncRNAs) exhibit lineage-specific expression, the vast majority remain functionally uncharacterized in the context of development. Here, we report the first described human embryonic stem cell (hESC) lines to repress (CRISPRi) or activate (CRISPRa) transcription during differentiation into all three germ layers, facilitating the modulation of lncRNA expression during early development. We performed an unbiased, genome-wide CRISPRi screen targeting thousands of lncRNA loci expressed during endoderm differentiation. While dozens of lncRNA loci were required for proper differentiation, most differentially expressed lncRNAs were not, supporting the necessity for functional screening instead of relying solely on gene expression analyses. In parallel, we developed a clustering approach to infer mechanisms of action of lncRNA hits based on a variety of genomic features. We subsequently identified and validated FOXD3-AS1 as a functional lncRNA essential for pluripotency and differentiation. Taken together, the cell lines and methodology described herein can be adapted to discover and characterize novel regulators of differentiation into any lineage

Metabolites of the gut microbiota involved in the autism spectrum disorder

En los últimos años, ha habido un aumento de los estudios que buscan comprender la relación existente entre el microbiota intestinal (MI) con el trastorno del espectro autista (TEA), que debe producirse a través del eje microbiota-intestino-cerebro. A pesar de que los distintos autores señalan que los cambios encontrados en distintos filos, familias y géneros bacterianos están implicados en el TEA, no hay consenso científico a día de hoy. Algunos autores apuntan a la posible relación existente entre dichas poblaciones bacterianas con ciertos productos de excreción o metabolitos como el ácido propiónico ya que aparecen con frecuencia en niños con TEA. Aunque en los últimos años la MI comienza a acumular evidencia científica, en términos de neurociencia, el estudio de la metabolómica asociada a la misma y los mecanismos mediante los cuales estos metabolitos pueden influir en la aparición y desarrollo del TEA aún permanece en sus primeros estadios.In recent years, there has been an increase in studies that seek to understand the relationship between gut microbiota (GM) with the behavior of people with autism spectrum disorders (ASD), which must occur through the microbiota-gut-brain axis. Although the different authors point out that the changes found in different phyla, families and bacterial genera are involved in ASD, there is no scientific consensus to date. Some authors point to the possible relationship between these bacterial populations with certain products of excretion or metabolites such as propionic acid since they frequently appear in children with ASD. Although in recent years the GM has begun to accumulate scientific evidence, in terms of neuroscience, the study of the metabolomics associated with it and the mechanisms by which these metabolites can influence the appearance and development of ASD remains in its first stages

Parallel evolutionary biclustering of short-term electric energy consumption

Presentación realizada en el marco del Proyecto PINV18-661: Análisis de la eficiencia energética en edificios no residenciales mediante técnicas metaheurísticas y de inteligencia artificial.CONACYT - Consejo Nacional de Ciencias y TecnologíaPROCIENCI

Oxaliplatin in combination with liver-specific expression of interleukin 12 reduces the immunosuppressive microenvironment of tumours and eradicates metastatic colorectal cancer in mice

BACKGROUND AND AIMS: New options are needed for the management and prevention of colorectal cancer liver metastases. Interleukin 12 (IL-12) is an immunostimulatory cytokine with proven antitumour effect in animal models. Despite evidence indicating its biological effect in humans, neither the recombinant protein nor gene therapy vectors expressing IL-12 have shown a relevant benefit in patients with cancer. OBJECTIVE: To develop a new approach to overcome the difficulties in obtaining a suitable expression pattern and the immunosuppressive milieu in the tumours which contribute to this poor performance. METHODS: A high-capacity ('gutless') adenoviral vector carrying a liver-specific, mifepristone (Mif)-inducible system for the expression of IL-12 (HC-Ad/RUmIL-12) was used in combination with chemotherapy. Tumours were established in the liver of C57BL/6 mice by inoculation of MC38 colon cancer cells. RESULTS: Intrahepatic injection of HC-Ad/RUmIL-12 and tailored induction regimens allowed the maintenance of safe and efficient levels of IL-12 in vivo. An individualised, stepwise increase in the dose of Mif (125-4000 μg/kg) was needed to compensate for the progressive but transient downregulation of the inducible system. Repeated cycles of Mif induction (every 24 h for 10 days) were needed for optimal tumour eradication. However, complete protection against tumour rechallenge was seen in < 25% of the animals. The administration of oxaliplatin (5 mg/kg intraperitoneally) 3 days before starting the induction regimen achieved efficient elimination of liver metastases with a single cycle of IL-12 induction, and improved protection against tumour rechallenge. This was associated with a shift in the tumour microenvironment towards a more pro-immunogenic phenotype, with an increase in the CD8+/T regulatory cell ratio and a reduction in myeloid-derived suppressor cells. These effects were not seen with 5-fluorouracil, irinotecan or gemcitabine

EZH2 endorses cell plasticity to non-small cell lung cancer cells facilitating mesenchymal to epithelial transition and tumour colonization

CGL was funded by the Consejería de Salud y Familias, Junta de Andalucía (RH-0139-2020) and SG-P is funded by Instituto de Salud Carlos III (CP19/00029, PI15/00336, PI19/01533). JAM is supported by RTI2018.101309B-C22 funded by MCIN/AEI/10.13039/501100011033/FEDER “Una manera de hacer Europa” and by the Chair “Doctors Galera-Requena in cancer stem cell research”. PCS is funded by Ministerio de Ciencia e Innovación (grant PID2020-119032RB-I00) and FEDER/Junta de Andalucía-Consejería de Transformación Económica, Industria, Conocimiento y Universidades (grants P20_00335 and B‐CTS‐40‐UGR20). The Landeira lab is supported by the Spanish ministry of science and innovation (PID2019-108108-100, EUR2021-122005), the Andalusian regional government (PC-0246-2017, PIER-0211-2019, PY20_00681) and the University of Granada (A-BIO-6-UGR20) grants.Reversible transition between the epithelial and mesenchymal states are key aspects of carcinoma cell dissemination and the metastatic disease, and thus, characterizing the molecular basis of the epithelial to mesenchymal transition (EMT) is crucial to find druggable targets and more effective therapeutic approaches in cancer. Emerging studies suggest that epigenetic regulators might endorse cancer cells with the cell plasticity required to conduct dynamic changes in cell state during EMT. However, epigenetic mechanisms involved remain mostly unknown. Polycomb Repressive Complexes (PRCs) proteins are well-established epigenetic regulators of development and stem cell differentiation, but their role in different cancer systems is inconsistent and sometimes paradoxical. In this study, we have analysed the role of the PRC2 protein EZH2 in lung carcinoma cells. We found that besides its described role in CDKN2A-dependent cell proliferation, EZH2 upholds the epithelial state of cancer cells by repressing the transcription of hundreds of mesenchymal genes. Chemical inhibition or genetic removal of EZH2 promotes the residence of cancer cells in the mesenchymal state during reversible epithelial–mesenchymal transition. In fitting, analysis of human patient samples and tumour xenograft models indicate that EZH2 is required to efficiently repress mesenchymal genes and facilitate tumour colonization in vivo. Overall, this study discloses a novel role of PRC2 as a master regulator of EMT in carcinoma cells. This finding has important implications for the design of therapies based on EZH2 inhibitors in human cancer patients.Junta de Andalucía (RH-0139-2020)Instituto de Salud Carlos III (CP19/00029, PI15/00336, PI19/01533)MCIN/AEI/10.13039/501100011033/FEDER “Una manera de hacer Europa” RTI2018.101309B-C22Chair “Doctors Galera-Requena in cancer stem cell research”Ministerio de Ciencia e Innovación (grant PID2020-119032RB-I00)FEDER/Junta de Andalucía-Consejería de Transformación Económica, Industria, Conocimiento y Universidades (grants P20_00335 and B‐CTS‐40‐UGR20)Spanish ministry of science and innovation (PID2019-108108-100, EUR2021-122005)Andalusian regional government (PC-0246-2017, PIER-0211-2019, PY20_00681)University of Granada (A-BIO-6-UGR20

REPORT ON THE 2020 ICCAT WORKSHOP ON SMALL TUNAS BIOLOGY STUDIES FOR GROWTH AND REPRODUCTION.

SUMMARY This report describes the 2020 ICCAT workshop on small tunas biology studies for growth and reproduction, hosted by the Instituto Español de Oceanografía, Málaga, Spain. The major objectives of the workshop were: 1) starting the creation of ageing and reproduction reference sets and, 2) providing more training for the ongoing sample collection and processing to the teams involved in these studies. As approved by the SCRS in 2017, the Small Tuna Species Group intersessional meeting decided to prioritize the collection of biological samples aiming at growth, maturity and stock structure studies on three species: little tunny (Euthynnus alletteratus), Atlantic Bonito (Sarda sarda) and wahoo (Acanthocybium solandri), based on their economic importance and the lack of knowledge on their biology. This work will contribute to the next major advance in the assessment of these three species. RÉSUMÉ Le présent rapport décrit l'atelier de l’ICCAT tenu en 2020 sur les études de la biologie des thonidés mineurs pour la croissance et la reproduction, organisé par l'Instituto Español de Oceanografía, à Malaga, en Espagne. Les principaux objectifs de l'atelier étaient les suivants : 1) commencer à créer des ensembles de référence sur la détermination de l’âge et la reproduction et 2) fournir une formation plus poussée sur la collecte et le traitement des échantillons aux équipes participant à ces études. Tel qu’approuvé par le SCRS en 2017, lors de la réunion intersessions du Groupe d'espèces sur les thonidés mineurs, il a été décidé de donner la priorité à la collecte d'échantillons biologiques visant à étudier la croissance, la maturité et la structure des stocks de trois espèces : la thonine commune (Euthynnus alletteratus), la bonite à dos rayé (Sarda) et le thazard-bâtard (Acanthocybium solandri), sur la base de leur importance économique et des connaissances lacunaires sur leur biologie. Ces travaux contribueront à la prochaine grande avancée dans l'évaluation de ces trois espèces. RESUMEN Este informe describe el taller de ICCAT de 2020 sobre estudios de biología de pequeños túnidos para crecimiento y reproducción, acogido por el Instituto Español de Oceanografía en Málaga, España. Los principales objetivos del taller eran: 1) empezar la creación de conjuntos de referencia de determinación de la edad y reproducción y 2) facilitar más formación a los equipos involucrados en estos estudios para la recopilación de muestras y procesamiento en curso. Como aprobó el SCRS en 2017, en la Reunión intersesiones del Grupo de especies de pequeños túnidos se decidió priorizar la recopilación de muestras biológicas con miras a estudios de crecimiento, madurez y estructura del stock de tres especies: bacoreta (Euthynnus alletteratus), bonito (Sarda sarda) y peto (Acanthocybium solandri), basándose en su importancia económica y la falta de conocimientos sobre su biología. Este trabajo contribuirá a avanzar en la próxima evaluación de estas tres especies.Versión del edito