MAX mutant small-cell lung cancers exhibit impaired activities of MGA-dependent noncanonical polycomb repressive complex

The MYC axis is disrupted in cancer, predominantly through activation of the MYC family oncogenes but also through inactivation of the MYC partner MAX or of the MAX partner MGA. MGA and MAX are also members of the polycomb repressive complex, ncPRC1.6. Here, we use genetically modified MAX-deficient small-cell lung cancer (SCLC) cells and carry out genome-wide and proteomics analyses to study the tumor suppressor function of MAX. We find that MAX mutant SCLCs have ASCL1 or NEUROD1 or combined ASCL1/NEUROD1 characteristics and lack MYC transcriptional activity. MAX restitution triggers prodifferentiation expression profiles that shift when MAX and oncogenic MYC are coexpressed. Although ncPRC1.6 can be formed, the lack of MAX restricts global MGA occupancy, selectively driving its recruitment toward E2F6-binding motifs. Conversely, MAX restitution enhances MGA occupancy to repress genes involved in different functions, including stem cell and DNA repair/replication. Collectively, these findings reveal that MAX mutant SCLCs have either ASCL1 or NEUROD1 or combined characteristics and are MYC independent and exhibit deficient ncPRC1.6-mediated gene repression.We thank Isabel Bartolessis for technical assistance, the confocal facility (Carmen Casals) and the RNA-sequencing genomic facility (Anna Esteve) for important services. Funding: This work was supported by Spanish grant SAF2017-82186-RAEI/FEDER (UE) (to MSC) from the MINECO and a grant from the Fundación Científica Asociación Española Contra el Cancer- GCB14142170MONT (to MSC). M Torres-Diz was supported by the FPI-fellowship: BES- 2012-054579, P Llabata by the FPI-fellowship: BES-2015-072204 and by the European Association for Cancer Research Travel fellowship and L Tomas-Daza by the FPI-fellowship (number PRE2019-088005). BMJ is funded by Spanish Ministry of Science, Innovation, and Universities (MICINN) project number RTI2018-094788-A-I00 and by La Caixa Banking Foundation Junior Leader project (LCF/BQ/PI19/11690001). The proteomics analyses were performed in the IJC Proteomics Unit. The IJC Proteomics Unit is part of the Spanish Platform of Molecular and Bioinformatics Resources (ProteoRed), Instituto de Salud Carlos III (PT13/0001). Competing Interests: All authors declare no competing financial interests.Peer Reviewed"Article signat per 12 autors/es: Paula Llabata, Manuel Torres-Diz, Antonio Gomez, Laureano Tomas-Daza, Octavio A. Romero, Joaquim Grego-Bessa, Pere Llinas-Arias, Alfonso Valencia, Manel Esteller, Biola M. Javierre, Xiaoyang Zhang, and Montse Sanchez-Cespedes"Postprint (author's final draft

Histología uretral y vaginal en algunas hembras de mamíferos

El análisis de las características histológicas de la uretra y la vagina en hembras de mamíferos es útil para entender la fisiología y la patología de procesos como la continencia urinaria, la cópula y el parto. En este contexto, las especies más estudiadas en cuanto a la organización tisular de la uretra y vagina son la rata y la coneja. Es necesario estudiar con más detalle la organización tisular de la vagina y uretra en diferentes especies con fines de comparación. Tal información permitiría entender la diversidad funcional y conductual asociada a estos órganos. El presente documento reúne, compara y discute la información existente sobre las características histológicas de la uretra y la vagina en algunas hembras de mamíferos destacando aquellas de la coneja, modelo utilizado por nuestro grupo de investigación para estudiar la fisiología reproductiva y urinaria femenina

Accuracy, Reliability, and Comprehensiveness of ChatGPT-Generated Medical Responses for Patients With Nonalcoholic Fatty Liver Disease

: Nonalcoholic fatty liver disease (NAFLD) is an increasing global health problem and is expected to become the leading indication for liver transplantation.1 There are no approved NAFLD-specific pharmacotherapies, and lifestyle modification is the primary recommended therapy.2 Innovative approaches to facilitate the implementation and long-term maintenance of lifestyle changes are needed to address the challenging and complex nature of the management of NAFLD, which recently was renamed as metabolic dysfunction-associated steatotic liver disease, to overcome the limitations and stigma of the previous name.3,4 Artificial intelligence (AI)-powered chatbots have been shown to provide effective personalized support and education to patients, with the potential to complement health care resources. The OpenAI Foundation's AI chatbot, Chat Generative Pretrained Transformer (ChatGPT), has attracted worldwide attention for its remarkable performance in question-answer tasks.5-7 This study evaluated the accuracy, completeness, and comprehensiveness of chatGPT's responses to NAFLD-related questions, with the aim of assessing its performance in addressing patients' queries about the disease and lifestyle behaviors

Research on Roma communities in Spain in the European context: a documentary analysis

El Pueblo Gitano ha estado presente en la historia de Europa y de España, siendo habitual las referencias a él como colectivo vulnerable. Sin embargo, apenas se tiene conocimiento de su situación social desde un enfoque global o multidimensional, es decir, teniendo en cuenta su riesgo social en diferentes ámbitos, como empleo, formación, ingresos, vivienda, salud, relaciones socio-familiares o participación. Mediante el análisis documental o bibliográfico, este trabajo pretende avanzar en esta línea, realizando una revisión sistemática de la situación de la investigación sobre este colectivo en el contexto europeo, al tiempo que se profundiza en la información que aportan los estudios en España sobre su situación social multidimensional. Los resultados obtenidos desvelan que mientras en Europa el interés científico se centra en su integración, destacando los estudios sobre participación ciudadana, en España priman los estudios que abordan dimensiones relacionadas con sus procesos de inclusión/exclusión, especialmente el de la educación.Roma people have been present for centuries in the history of Europe and Spain; being usual references to them as a vulnerable community. Nevertheless, there is barely any knowledge about their social situation from a holistic or multidimensional approach. It means, taking into account their social risk at different areas such as: employment, training, income, housing, health, social and family relations or participation. This article aims to improve the knowledge of Roma community through the documentary or bibliographic analysis in two different ways. On the one hand, a research systematic review is implemented in the European framework. And on the other hand, research is conducted through multidimensional approach to different studies deepening the understanding of social situation of Roma in Spain. The outcomes reveal that in Europe scientific interest is focused on their social integration; studies on participation are highlighted. However, in Spain several researches show that prevailing dimensions are related to their Social Inclusion / Exclusion processes; mainly about Education

Optimised low-thrust mission to the Atira asteroids

Atira asteroids are recently-discovered celestial bodies characterised by orbits lying completely inside the heliocentric orbit of the Earth. The study of these objects is difficult due to the limitations of ground-based observations: objects can only be detected when the Sun is not in the field of view of the telescope. However, many asteroids are expected to exist in the inner region of the Solar System, many of which could pose a significant threat to our planet. In this paper, a small, low-cost, mission to visit the known Atira asteroids and to discover new Near Earth Asteroids (NEA) is proposed. The mission is realised using electric propulsion. The trajectory is optimised to maximise the number of visited asteroids of the Atira group using the minimum propellant consumption. During the tour of the Atira asteroids an opportunistic NEA discovery campaign is proposed to increase our knowledge of the asteroid population. The mission ends with a transfer to an orbit with perihelion equal to Venus's orbit radius. This orbit represents a vantage point to monitor and detect asteroids in the inner part of the Solar System and provide early warning in the case of a potential impact

Empowering CO2 Eco-Refrigeration with Colossal Breathing-Caloric-Like Effects in MOF-508b

publishedVersio

Cambios en la condición cosmética de la sonrisa de una paciente por medio de alargamiento coronario

ResumenExisten situaciones periodontales importantes a evaluar durante el tratamiento: la sonrisa de encía, discrepancia del borde marginal y las carencias de papilas. En algunas de estas situaciones, la alteración de la posición de los dientes, corrige el problema estético; mientras que en otros pacientes la cirugía gingival es el plan de tratamiento óptimo para mejorar la apariencia estética del diente. El alargamiento de corona es un procedimiento quirúrgico, incluido dentro de la cirugía periodontal a colgajo, consistente en eliminar encía y hueso para crear una corona clínica más larga y desplazar en sentido apical el margen gingival. El objetivo de esta cirugía es solucionar el problema de las llamadas coronas clínicas cortas, sin alterar el espacio biológico de inserción. (Duazary 2009-II 134-140)Abstract There are important periodontal situations to evaluate during treatment: the smile of gum, discrepancy of the marginal edge and papillae deficiencies. In some of these situations, alteration of the position of the teeth, corrects the aesthetic problem, while in other patients gingival surgery is the best treatment plan to improve the aesthetic appearance of a patient. The crown lengthening is a surgical procedure, including within the periodontal flap surgery, consisting of removing gum and bone to create a crown longer clinical crown and move apically the gingival margin. The goal of this surgery is to solve the problem of so-called short clinical crowns without altering the biological space of insertion.Key words: Crown Lengthening; Gingivectomy; Altered passive eruption

Galanin N-Terminal fragment (1-15) enhances the antidepressant effects of the 5-HT1A receptor agonist 8-OH-DPAT in the Forced Swimming Test.

Galanin and Galanin (1-15) [GAL(1-15)] are implicated in anxiety- and depression related behaviors. Moreover, Galanin modulates 5-HT1A receptor (5-HT1AR) function at autorreceptor and postsynaptic level in the brain. In this study, we have analysed the ability of GAL(1-15) to modulate the effects of the 8-OH-DPAT agonist in the Forced Swimming Test (FST). Groups of rats were assessed in the FST. In the first set of experiments, to evaluate the interactions of 8-OH-DPAT and GAL(1-15), rats received subcutaneously (s.c) the effective doses of 8-OH-DPAT (0.25mg/Kg) 60min before the test and intracerebroventricularly (icv) GAL(1-15)1nmol 15min before the tests alone or in combination. In the second set of experiments, groups of rats received s.c. 8-OH-DPAT (0.125mg/Kg), icv GAL(1-15) 1nmol and icv the GALR2 antagonist M871 3 nmol alone or in combination. The locomotor activity was analysed in the open field test. GAL(1-15) 1nmol enhanced the antidepressant-like effects mediated by the effective dose of the 8-OH-DPAT. GAL(1-15) significantly decreased the immobility (p<0.05) and climbing (p<0.05) and increased the swimming (p<0.01) behaviour induced by an effective dose of 8-OH-DPAT (0.25mg/Kg) in FST. Moreover, after coadministration of GAL(1-15) and threshold dose of 8-OH-DPAT (0.125mg/Kg) a significant decreased appeared in immobility (p<0.01) and climbing (p<0.01) and increased the swimming behavior (p<0.001) vs 8-OH-DPAT group. Moreover, M871 blocked completely this interaction. These results indicate that GAL(1-15) enhances the antidepressant effects induced by 8-OH-DPAT in the FST. These findings may give the basis for the development of novel therapeutic drugs. This study was supported by Junta de Andalucía CVI6476.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. This study was supported by Junta de Andalucía CVI6476

Biometric differences between several populations of Cordulegaster boltonii (Odonata: Cordulegastridae) in Ibero-Maghrebian area

Biometric data of the exuviae of female larvae of the dragonfly Cordulegaster boltonii collected in Portugal, Spain and Morocco were analysed to determine whether the size of three exuvial structures measured differed depending on the geographic localities of the populations. Based on the results recorded for the 16 populations studied, head width was negatively correlated with latitude and the greatest length of the gonapophysis was recorded for the Iberian populations at the centre of this peninsula. Multivariate cluster analysis revealed a clear separation of the Moroccan population. A second cluster separated the southernmost population (Sierra Nevada) from the remaining Iberian populations. Four population groups were distinguished: those located in watercourses in the north and central area of the Iberian Peninsula, those in Iberian watercourses in the East and Middle South, the Sierra Nevada and North Morocco. Some of these results coincide with the results of genetic studies of other authors

La investigación sobre comunidades gitanas en España en el contexto europeo: un análisis documental

El Pueblo Gitano ha estado presente en la historia de Europa y de España, siendo habitual las referencias a él como colectivo vulnerable. Sin embargo, apenas se tiene conocimiento de su situación social desde un enfoque global o multidimensional, es decir, teniendo en cuenta su riesgo social en diferentes ámbitos, como empleo, formación, ingresos, vivienda, salud, relaciones socio-familiares o participación. Mediante el análisis documental o bibliográfico, este trabajo pretende avanzar en esta línea, realizando una revisión sistemática de la situación de la investigación sobre este colectivo en el contexto europeo, al tiempo que se profundiza en la información que aportan los estudios en España sobre su situación social multidimensional. Los resultados obtenidos desvelan que mientras en Europa el interés científico se centra en su integración, destacando los estudios sobre participación ciudadana, en España priman los estudios que abordan dimensiones relacionadas con sus procesos de inclusión/exclusión, especialmente el de la educación