Detection of gamma rays of likely jet origin in Cygnus X-1

Aims: Probe the high-energy ($>$60 MeV) emission from the black hole X-ray binary system, Cygnus X-1, and investigate its origin. Methods: We analysed 7.5 yr of data by Fermi/LAT with the latest PASS8 software version. Results: We report the detection of a signal at $\sim$8 $\sigma$ statistical significance spatially coincident with Cygnus X-1 and a luminosity above 60 MeV of 5.5$\times$10$^{33}$ erg s$^{-1}$. The signal is correlated with the hard X-ray flux: the source is observed at high energies only during the hard X-ray spectral state, when the source is known to display persistent, relativistic radio emitting jets. The energy spectrum, extending up to $\sim$20 GeV without any sign of spectral break, is well fitted by a power-law function with a photon index of 2.3$\pm$0.2. There is a hint of orbital flux variability, with high-energy emission mostly coming around the superior conjunction. Conclusions: We detected GeV emission from Cygnus X-1 and probed that the emission is most likely associated with the relativistic jets. The evidence of flux orbital variability points to the anisotropic inverse Compton on stellar photons as the mechanism at work, thus constraining the emission region to a distance $10^{11}-10^{13}$ cm from the black hole.Comment: accepted A\&A (9 pages and 7 figures

MAGIC VHE Gamma-Ray Observations Of Binary Systems

There are several types of Galactic sources that can potentially accelerate charged particles up to GeV and TeV energies. We present here the results of our observations of the source class of gamma-ray binaries and the subclass of binary systems known as novae with the MAGIC telescopes. Up to now novae were only detected in the GeV range. This emission can be interpreted in terms of an inverse Compton process of electrons accelerated in a shock. In this case it is expected that protons in the same conditions can be accelerated to much higher energies. Consequently they may produce a second component in the gamma-ray spectrum at TeV energies. The focus here lies on the four sources: nova V339 Del, SS433, LS I +61 303 and V404 Cygni. The binary system LS I +61 303 was observed in a long-term monitoring campaign for 8 years. We show the newest results on our search for superorbital variability, also in context with contemporaneous optical observations. Furthermore, we present the observations of the only super-critical accretion system known in our galaxy: SS433. Finally, the results of the follow-up observations of the microquasar V404 Cygni during a series of outbursts in the X-ray band and the ones of the nova V339 Del will be discussed in these proceedings.Comment: Proceedings of the 35th International Cosmic Ray Conference (ICRC 2017), Bexco, Busan, Korea (arXiv:1708.05153

Gamma rays detected from Cygnus X-1 with likely jet origin

Aims. We probe the high-energy (>60 MeV) emission from the black hole X-ray binary system, Cygnus X-1, and investigate its origin. Methods. We analyzed 7.5 yr of data by Fermi-LAT with the latest Pass 8 software version. Results. We report the detection of a signal at ~8σ statistical significance that is spatially coincident with Cygnus X-1 and has a luminosity of 5.5 × 1033 erg s-1, above 60 MeV. The signal is correlated with the hard X-ray flux: the source is observed at high energies only during the hard X-ray spectral state, when the source is known to display persistent, relativistic radio-emitting jets. The energy spectrum, extending up to ~20 GeV without any sign of spectral break, is well fit by a power-law function with a photon index of 2.3 ± 0.2. There is a hint of orbital flux variability, with high-energy emission mostly coming around the superior conjunction. Conclusions. We detected GeV emission from Cygnus X-1 and probed that the emission is most likely associated with the relativistic jets. The evidence of flux orbital variability indicates the anisotropic inverse-Compton on stellar photons as the mechanism at work, thus constraining the emission region to a distance 1011-1013 cm from the black hole

Vitamin D effects on human colon normal and tumour organoids

Trabajo presentado en FEBS Open Bio, celebrado en Lisboa (Portugal) del 09 al 14 de julio de 2022.Many studies indicate an association between vitamin D deficiency and increased colorectal cancer risk and, specially, mortality. Accordingly, the active vitamin D metabolite 1a,25-dihydroxyvitamin D3 (calcitriol) inhibits the proliferation and promotes the differentiation of colon carcinoma cells and of other tumour cell types, and also has antitumour effects in animal models of colon cancer. These results prompted us to analyse the effects of calcitriol on human colon normal and cancer stem cells. To this end, we established a living biobank of patient-derived colon organoids generated from the tumour mass and from the adjacent healthy tissue obtained from surgical biopsies. Organoids are a three-dimensional culture system of normal or cancer stem cells and their progeny with a self-organized multicellular structure. By immunohistochemistry and RNAscope in situ hybridization, we found that vitamin D receptor is expressed in LGR5+ colon stem cells in human tissue and in normal and tumour organoid cultures. RNA-sequencing assays showed that both organoid types respond differentially to calcitriol with profound and contrasting changes in their transcriptomic profiles. This was confirmed in an independent series of patient-derived organoids by RT-qPCR assays. In normal organoids, calcitriol upregulates stemness-related genes and inhibits cell proliferation. In contrast, in tumour organoids calcitriol has little effect on stemnessrelated genes, while it induces differentiation-associated genes, and variably reduces cell proliferation. Concordantly, electron microscopy analyses showed that calcitriol does not affect the blastic cell phenotype in normal organoids, but it induces a series of differentiated features in tumour organoids. These results indicate that calcitriol maintains the undifferentiated phenotype of human normal colon stem cells (homeostatic action), while it promotes the differentiation of colon cancer stem cells (anticancer action).

Sur8, a determinant protein in colorectal cancer tumor progression

Resumen del trabajo presentado en el 43rd Annual Meeting of the SEBBM, celebrado en Barcelona (España) del 19 al 21 de julio de 2021.Colorectal cancer (CRC) has the highest incidence rate in the Spanish population. The most important challenge consists on the discovery of efficient disease treatments, due to high mortality rates in highly developed stages. Sur8 is a scaffold protein that positively modulates ERK signaling pathway, which has a major role in the progression and metastasis in colorectal cancer. The main goals of our research are to determine the role that Sur8 plays in the development and progression of CRC and to analyze its possible therapeutic potential. For this purpose, our group has developed an inducible conditional mouse model msur8f/fVillinCreERT2. In order to determine Sur8 action in the colonic tissue, we have developed organoids from the colon epithelium of healthy mice and have analyzed gene expression pattern by an RNAseq approach. Sur8 KO affects oncogenic CRC transcription factors expression, as well as the modulation of some Wnt pathway regulators. In regard to miRNA data, we have observed deregulation of miRNAs related to CRC in Sur8 KO organoids. To determine the role that Sur8 plays in the development and progression of CRC, we have subjected our inducible conditional mice to chemical carcinogenesis and we have observed that Sur8 KO males display less and smaller tumors and do not present any adenocarcinoma. In addition, we have carried out Sur8 silencing in human CRC cell lines by infection with constitutive shRNA lentiviruses. We have observed that Sur8 silencing produces decreases of cell tumor proliferation, and reduction of p-ERK levels. Finally, we are evaluating the effects of putative therapeutic agents against Sur8 in human CRC cell lines. Concretely, we are testing Celastrol, which has been described that binds and blocks the action of Sur8 in vitro. We have observed that Celastrol treatment diminishes the cell tumor proliferation in this model. Altogether, our results indicate that Sur8 may have a determinant role in CRC progression and that Sur8 could be a potential molecular target for the design of novel strategies against CRC

Sustainability and social responsibility strategies at spanish universities: an assessment tool

El grupo de Evaluación de la sostenibilidad universitaria de la Comisión Sectorial de Calidad Ambiental, Desarrollo Sostenible y Prevención de Riesgos (CADEP) de la CRUE viene trabajando desde 2007 en el estudio sistemático de las iniciativas de sostenibilidad en las universidades españolas. Entre 2010 y 2011 ha desarrollado el estudio “Evaluación de las políticas universitarias de sostenibilidad como facilitadoras para el desarrollo de los campus de excelencia internacional (CEI)” en el que se han definido ámbitos e indicadores con los que medir la contribución de las universidades españolas a la sostenibilidad. Estos indicadores constituyen un marco evaluativo del grado de avance de las políticas de sostenibilidad, haciendo los progresos más visibles para la comunidad universitaria y la sociedad. Para probar esta herramienta se consultaron 31 universidades que rellenaron el cuestionario y fueron visitadas para recoger sus dudas y sugerencias y, además, realizar un acercamiento a los programas de sostenibilidad en el sistema universitario español. También se entrevistaron a los responsables institucionales y técnicos de estos programas. En general, las universidades estudiadas presentan un mayor avance en actuaciones relacionadas con la sensibilización ambiental, los residuos y la docencia. En menor medida han implementado medidas sobre responsabilidad social, evaluación del impacto ambiental, agua y compra verde.Since 2007 the group on Sustainability Assessment of the Spanish Rectors’ Conference is working on the definition of a framework for the assessment and benchmarking of environmental and sustainable activities and strategies at Spanish Universities. During 2010 and 2011 it has carried out a study called “Evaluation of sustainability policies and their relation to the International Campus of Excellence program”. The main results from this study have led to the identification of a system of indicators to measure the progress of Spanish Universities in their contribution to sustainability and social responsibility. 31 universities have participated in the study by filling in the initial questionnaire. Moreover, they have all been interviewed by the research team. We can say that, in general, these universities present a good level of environmental awareness, curricular greening programs, and operational actions, mainly related to waste management.Grupo FORCE (HUM-386). Departamento de Didáctica y Organización Escolar de la Universidad de Granada

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele