A psychometric study of a Spanish version of the negative acts questionnaire-revised: confirmatory factor analysis.

Background: The NAQ (Negative Acts Questionnaire) has been widely used in more than 40 countries to measure the mobbing phenomenon. This research aims to present a psychometric study based on the Spanish version of the NAQ-R carried out by González-Trijueque and Graña (2013). As opposed to the original scale, this sample contains 23 items and a three-dimension model (personal bullying, work-related bullying, and physically intimidating forms of bullying). Methods: We used a heterogeneous occupational sample of 2,538 Spanish employees to analyze internal consistency and concurrent validity. In addition, a Confirmatory Factor Analysis was carried out based on the GLS (generalized least squares) method. Results: Results showed high internal reliability (Cronbach’s alpha = 0.91) and high correlations containing clinical symptoms, burn-out indicators, and coping resources. The Confirmatory Factor Analysis developed upon the heterogeneous occupational sample validates the three-dimension structure in the Spanish version of the NAQ-R aimed to measure harassment behaviors at the workplace. Conclusion: The NAQ-R reaffirms its validity and reliability as a measure for mobbing-related behaviors. Hence, the scale may become a useful tool in research and forensic practice.post-print779 K

Paleogeografía sísmica de zonas costeras en la Península Ibérica: su impacto en el análisis de terremotos antiguos e históricos en España

This paper presents three examples of ancient earthquakes occurring in coastal areas of the S and SE of the Iberian Peninsula (218 BC, AD 40-60 and AD 1048) with the aim of illustrating the use of geological and archaeological data in their macroseismic characterization. Historical information for ancient earthquakes that occurred in Spain prior to the 10th century is scarce or non-existent. This paper shows that the current state of knowledge on palaeoseismology and archaeoseismology on these ancient events clearly exceeds the existing historical information allowing the increase of macroseismic information points by using the ESI-07 scale (Environmental Seismic Intensity). Consequently, the geologic analyses of ancient earthquakes contribute to their understanding and parametric evaluations, and improve further advances in seismic hazard assessments. The most significant issue outlined in the present paper is the analysis of the ancient palaeogeography of the affected areas. The studied examples analysed were located in open estuarine areas that have been filled by fluvial sediments or anthropogenic fills over time. The effects of the 218 BC earthquake-tsunami event in the Gulf of Cadiz are analysed in estuarine areas, and especially in the ancient Roman Lagus Ligustinus (Guadalquivir Depression marshes); the effects of the earthquake in AD 40-60 is analysed in the old Roman city of Baelo Claudia located in the Bolonia Bay (Strait of Gibraltar); and the effects of the earthquake of AD 1048on the ancient Sinus Ilicitanus (Bajo Segura Depression) during Muslim times. Descriptions from Roman and Arabic geographers are cross-checked with existing palaeogeographic models based on geological data. This type of analysis results in ancient macroseismic scenarios for the interpretation of theoretical distributions of intensities and environmental effects supporting the concept of “seismic palaeogeography” proposed in this paperEl presente trabajo recoge tres ejemplos de terremotos antiguos (218 AC, 40-60 AD y 1048 AD) ocurridos en zonas litorales del S y SO de la Península Ibérica con la intención de ilustrar el uso de datos geológicos y ar¬queológicos en la caracterización macrosísmica de los mismos. En la mayor parte de los sísmos ocurridos con anterioridad al siglo X d.C. la información documental histórica que se posee es muy escasa o inexistente. El presente trabajo muestra que el actual estado de conocimiento en paleosismología y arqueosismologia sobre este tipo de terremotos sobrepasa con creces la información documental histórica, permitiendo la multiplica¬ción de los puntos de información macrosísmica mediante el uso de la escala ESI-07 (Environmental Seismic Intensity). Consecuentemente, el análisis geológico de los terremotos antiguos mejora su conocimiento y análisis paramétrico, permitiendo avanzar la evaluación de la peligrosidad sísmica de las zonas afectadas. El aspecto que se pone de especial relieve en este trabajo es el análisis de la paleogeografía existente en la antigüedad, ya que todas las zonas (afectadas) analizadas en este trabajo corresponden a zonas estuarinas abiertas que se han ido rellenado por aportes fluviales o de forma artificial con el tiempo. Se analizan los efectos del terremoto de 218 AC en las zonas estuarinas del Golfo de Cádiz y muy especialmente en el antiguo Lacus Ligustinus (marismas del Guadalquivir) durante época romana; los efectos del terremoto de 40-60 AD en la antigua Bahía de Baelo Claudia (Estrecho de Gibraltar); y los efectos del terremoto de 1048 AD en el antiguo Sinus ilicitanus (Depresión del Bajo Segura) durante época musulmana. Se han cotejado descripciones de geógrafos romanos y árabes con modelos basados en datos geológicos. Este tipo de análisis ha permitido generar antiguos escenarios macrosísmicos basados en la paleogeografía y reinterpretar las distribuciones teóricas de intensidades y los efectos ambientales de los terremotos estudiados que es a lo que se refiere el concepto de “paleogeografía sísmica” propuesto en este trabajoThis work has been funded by the Spanish-FEDER research projects CGL2012-37281 C02.01 (QTECTBETICA-USAL), CGL2012-33430 (CSIC) and CGL2013-42847-R (UNED

Prevention of diabetes in overweight/obese children through a family based intervention program including supervised exercise (PREDIKID project): study protocol for a randomized controlled trial

Background: The global pandemic of obesity has led to an increased risk for prediabetes and type-2 diabetes (T2D). The aims of the current project are: (1) to evaluate the effect of a 22-week family based intervention program, including supervised exercise, on insulin resistance syndrome (IRS) risk in children with a high risk of developing T2D and (2) to identify the profile of microRNA in circulating exosomes and in peripheral blood mononuclear cells in children with a high risk of developing T2D and its response to a multidisciplinary intervention program including exercise. Methods: A total of 84 children, aged 8-12 years, with a high risk of T2D will be included and randomly assigned to control (N = 42) or intervention (N = 42) groups. The control group will receive a family based lifestyle education and psycho-educational program (2 days/month), while the intervention group will attend the same lifestyle education and psycho-educational program plus the exercise program (3 days/week, 90 min per session including warm-up, moderate to vigorous aerobic activities, and strength exercises). The following measurements will be evaluated at baseline prior to randomization and after the intervention: fasting insulin, glucose and hemoglobin A1c; body composition (dual-energy X-ray absorptiometry); ectopic fat (magnetic resonance imaging); microRNA expression in circulating exosomes and in peripheral blood mononuclear cells (MiSeq; Illumina); cardiorespiratory fitness (cardiopulmonary exercise testing); dietary habits and physical activity (accelerometry). Discussion: Prevention and identification of children with a high risk of developing T2D could help to improve their cardiovascular health and to reduce the comorbidities associated with obesity.The Spanish Ministry of Industry and Competitiveness (DEP2016-78377-R), by “Fondos Estructurales de la Unión Europea (FEDER), Una manera de hacer Europa.” and by the University of the Basque Country (GIU14/21). This work was also supported by grants from Spanish Ministry of Economy and Competitiveness (RYC-2010-05957; RYC- 2011-09011), Spanish Ministry of Education, Culture and Sports (FPU14/ 03329) and by the Education, Linguistic Policy and Culture Department of the Government of the Basque Country (PRE_2016_1_0057)

Endoglin, a novel biomarker and therapeutical target to prevent malignant peripheral nerve sheath tumor growth and metastasis.

PURPOSE Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft-tissue sarcomas that lack effective treatments, underscoring the urgent need to uncover novel mediators of MPNST pathogenesis that may serve as potential therapeutic targets. Tumor angiogenesis is considered a critical event in MPNST transformation and progression. Here, we have investigated whether endoglin (ENG), a TGF-β coreceptor with a crucial role in angiogenesis, could be a novel therapeutic target in MPNSTs. EXPERIMENTAL DESIGN ENG expression was evaluated in human peripheral nerve sheath tumor tissues and plasma samples. Effects of tumor cell-specific ENG expression on gene expression, signaling pathway activation and in vivo MPNST growth and metastasis were investigated. The efficacy of ENG targeting in monotherapy or in combination with MEK inhibition was analyzed in xenograft models. RESULTS ENG expression was found to be upregulated in both human MPNST tumor tissues and plasma circulating small extracellular vesicles. We demonstrated that ENG modulates Smad1/5 and MAPK/ERK pathway activation and pro-angiogenic and pro-metastatic gene expression in MPNST cells and plays an active role in tumor growth and metastasis in vivo. Targeting with ENG-neutralizing antibodies (TRC105/M1043) decreased MPNST growth and metastasis in xenograft models by reducing tumor cell proliferation and angiogenesis. Moreover, combination of anti-ENG therapy with MEK inhibition effectively reduced tumor cell growth and angiogenesis. CONCLUSIONS Our data unveil a tumor-promoting function of ENG in MPNSTs and support the use of this protein as a novel biomarker and a promising therapeutic target for this disease.We apologize to those authors whose work could not be cited due to size limitations. We thank Dr. Eduard Serra, Dr. Conxi Lázaro and Dr. David Lyden for their support in the project. We also thank Héctor Tejero for his help in analyzing RNA-seq data. Dr. Peinado laboratory is funded by US Department of Defense (W81XWH-16-1-0131), Agencia Estatal de Investigación/Ministerio de Ciencia e Innovación (AEI/MCIN) (PID2020-118558RB-I00/AEI/10.13039/501100011033), Fundación Proyecto Neurofibromatosis, European Union’s Horizon 2020 research and innovation programme “proEVLifeCycle” under the Marie Skłodowska-Curie grant agreement No 860303, and Fundación Científica AECC. We are also grateful for the support of the Ministerio de Universidades (Programa de Formación de Profesorado Universitario (FPU)) for the fellowship FPU016/05356 awarded to T. González-Muñoz and to the Translational NeTwork for the CLinical application of Extracellular VesicleS (TeNTaCLES) RED2018-102411-T(AEI/10.13039/501100011033). A. Di Giannatale was supported during this work by a research gran Nuovo-Soldati Foundation. The CNIO, certified as Severo Ochoa Excellence Centre, is supported by the Spanish Government through the Instituto de Salud Carlos III.N

Comprehensive investigation of fission yields by using spallation- and (p,2p)-induced fission reactions in inverse kinematics

In the last decades, measurements of spallation, fragmentation and Coulex induced fission reactions in inverse kinematics have provided valuable data to accurately investigate the fission dynamics and nuclear structure at large deformations of a large variety of stable and non-stable heavy nuclei. To go a step further, we propose now to induce fission by the use of quasi-free (p,2p) scattering reactions in inverse kinematics, which allows us to reconstruct the excitation energy of the compound fissioning system by using the four-momenta of the two outgoing protons. Therefore, this new approach might permit to correlate the excitation energy with the charge and mass distributions of the fission fragments and with the fission probabilities, given for the first time direct access to the simultaneous measurement of the fission yield dependence on temperature and fission barrier heights of exotic heavy nuclei, respectively. The first experiment based on this methodology was realized recently at the GSI/FAIR facility and a detailed description of the experimental setup is given here.Comment: 4 pages, 15th International Conference on Nuclear Data for Science and Technology (ND2022

Los terremotos antiguos del conjunto arqueológico romano de Baelo Claudia (Cádiz, Sur de España): Quince años de investigación arqueosismológica

El presente trabajo ilustra el estado del conocimiento sobre arqueosismología en la antigua ciudad romana de Baelo Claudia (Tarifa, Cádiz) tras casi quince años de investigaciones. Esta antigua ciudad romana se vio afectada por dos importantes terremotos en los años 40–60 AD y 260–290 AD. El primero de ellos afectó en mayor grado a la parte baja (costera) de la ciudad provocando importantes cambios urbanísticos y arquitectónicos (monumentalización) en respuesta a las labores de reconstrucción. El segundo de ellos provocó una mayor destrucción, cuya ruina progresiva desembocó en el abandono definitivo de la ciudad en el 365–390 AD. Se catalogan, cartografían y describen la mayor parte de los Efectos Arqueológicos de los Terremotos (EAEs) del sector monumental de la ciudad, que testifican los efectos producidos por el terremoto ocurrido en el 260–90 AD. La cartografía de daños (EAEs) muestra la distribución y orientación de los daños en la zona baja de la ciudad, así como la ocurrencia de otros procesos cosísmicos, como deslizamientos y pequeños tsunamis. El análisis estructural del conjunto de daños orientados indica que la dirección de movimiento del terreno se produjo en una dirección dominante del SO al NE. Los análisis geoarqueológicos, así como importantes anomalías constructivas y funerarias, sugieren la intervención de tsunamis de escaso poder de penetración durante los dos terremotos, apuntando a la existencia de una fuente sísmica submarina común al SSO de la ciudad. Se han identificado diferentes fallas normales de dirección N-S en la zona de la Bahía de Bolonia, algunas de las cuales se prolongan hacia el interior del mar en la zona SSO de Baelo Claudia. Estas fallas presentan claras evidencias de actividad Cuaternaria y podrían considerarse como las fuentes sísmicas más probables para los dos antiguos terremotos que afectaron a la ciudad en época romana.Departamento de Geología, Escuela Politécnica Superior de Ávila, Universidad Salamanca, EspañaDepartamento de Geología y Geoquímica, Universidad Autónoma de Madrid, EspañaInstitut für Neotektonik und Naturgefahren, Universität Aachen, AlemaniaÁrea de Riesgos Naturales, Instituto Geológico y Minero de España, EspañaDepartment of Earth Sciences, University of Cambridge, Reino UnidoConjunto Arqueológico Romano de Baelo Claudia, Junta de Andalucía, EspañaDepartamento de Ingeniería del Terreno, Escuela Politécnica Superior de Ávila, Universidad de Salamanca, EspañaU.D. Geología, Universidad de Alcalá, EspañaDepartamento de Edafología, Universidad Politécnica de Madrid, EspañaDepartamento de Geología, Universidad de Salamanca, EspañaDepartamento de Geología, Museo Nacional de Ciencias Naturales, Españ

Senescence and Sexual Selection in a Pelagic Copepod

The ecology of senescence in marine zooplankton is not well known. Here we demonstrate senescence effects in the marine copepod Oithona davisae and show how sex and sexual selection accelerate the rate of ageing in the males. We show that adult mortality increases and male mating capacity and female fertility decrease with age and that the deterioration in reproductive performance is faster for males. Males have a limited mating capacity because they can fertilize < 2 females day−1 and their reproductive life span is 10 days on average. High female encounter rates in nature (>10 day−1), a rapid age-dependent decline in female fertility, and a high mortality cost of mating in males are conducive to the development of male choosiness. In our experiments males in fact show a preference for mating with young females that are 3 times more fertile than 30-day old females. We argue that this may lead to severe male-male competition for young virgin females and a trade-off that favours investment in mate finding over maintenance. In nature, mate finding leads to a further elevated mortality of males, because these swim rapidly in their search for attractive partners, further relaxing fitness benefits of maintenance investments. We show that females have a short reproductive period compared to their average longevity but virgin females stay fertile for most of their life. We interpret this as an adaptation to a shortage of males, because a long life increases the chance of fertilization and/or of finding a high quality partner. The very long post reproductive life that many females experience is thus a secondary effect of such an adaptation

RAB7 Controls Melanoma Progression by Exploiting a Lineage-Specific Wiring of the Endolysosomal Pathway

Although common cancer hallmarks are well established, lineage-restricted oncogenes remain less understood. Here, we report an inherent dependency of melanoma cells on the small GTPase RAB7, identified within a lysosomal gene cluster that distinguishes this malignancy from over 35 tumor types. Analyses in human cells, clinical specimens, and mouse models demonstrated that RAB7 is an early-induced melanoma driver whose levels can be tuned to favor tumor invasion, ultimately defining metastatic risk. Importantly, RAB7 levels and function were independent of MITF, the best-characterized melanocyte lineage-specific transcription factor. Instead, we describe the neuroectodermal master modulator SOX10 and the oncogene MYC as RAB7 regulators. These results reveal a unique wiring of the lysosomal pathway that melanomas exploit to foster tumor progression.M.S.S. is funded by Projects SAF2011-28317 and Consolider RNAREG from the Spanish Ministry of Economy and Innovation, R01CA125017 from the NIH, and a Team Science Award by the Melanoma Research Foundation. J.L.R.-P. and P.O.-R. are funded by grants FIS 11/025685 and FIS 11/1759, respectively, from the Spanish Ministry of Health. J.L.R.-P. was also supported by grant FMM-2008-106 of Fundación Mutua Madrileña, and P.O.-R. by Red Tematica de Investigacion Cooperativa en Cancer. D.A.-C. and E.P.-G. are recipients of Scientists in Training predoctoral fellowships from the Spanish Ministry of Science and Innovation. M.C. and P.K. are funded by predoctoral fellowships of Fundación La Caixa. E.R.-F. is the recipient of a postdoctoral fellowship from Fundación Científica de la Asociación Española Contra el Cáncer, and J.A.J. and H.-W.W. are funded by the American Cancer Society (RSG-12-076-01-LIB)

Integrative multi-omics analysis identifies a prognostic miRNA signature and a targetable miR-21-3p/TSC2/ mTOR axis in metastatic pheochromocytoma/ paraganglioma

Rationale: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that present variable outcomes. To date, no effective therapies or reliable prognostic markers are available for patients who develop metastatic PPGL (mPPGL). Our aim was to discover robust prognostic markers validated through in vitro models, and define specific therapeutic options according to tumor genomic features. Methods: We analyzed three PPGL miRNome datasets (n=443), validated candidate markers and assessed them in serum samples (n=36) to find a metastatic miRNA signature. An integrative study of miRNome, transcriptome and proteome was performed to find miRNA targets, which were further characterized in vitro. Results: A signature of six miRNAs (miR-21-3p, miR-183-5p, miR-182-5p, miR-96-5p, miR-551b-3p, and miR-202-5p) was associated with metastatic risk and time to progression. A higher expression of five of these miRNAs was also detected in PPGL patients’ liquid biopsies compared with controls. The combined expression of miR-21-3p/miR-183-5p showed the best power to predict metastasis (AUC=0.804, P=4.67·10-18), and was found associated in vitro with pro-metastatic features, such as neuroendocrine-mesenchymal transition phenotype, and increased cell migration rate. A pan-cancer multi-omic integrative study correlated miR-21-3p levels with TSC2 expression, mTOR pathway activation, and a predictive signature for mTOR inhibitor-sensitivity in PPGLs and other cancers. Likewise, we demonstrated in vitro a TSC2 repression and an enhanced rapamycin sensitivity upon miR-21-3p expression. Conclusions: Our findings support the assessment of miR-21-3p/miR-183-5p, in tumors and liquid biopsies, as biomarkers for risk stratification to improve the PPGL patients’ management. We propose miR-21-3p to select mPPGL patients who may benefit from mTOR inhibitors