HypoxamiRs Profiling Identify miR-765 as a Regulator of the Early Stages of Vasculogenic Mimicry in SKOV3 Ovarian Cancer Cells

Vasculogenic mimicry (VM) is a novel cancer hallmark in which malignant cells develop matrix-associated 3D tubular networks with a lumen under hypoxia to supply nutrients needed for tumor growth. Recent studies showed that microRNAs (miRNAs) may have a role in VM regulation. In this study, we examined the relevance of hypoxia-regulated miRNAs (hypoxamiRs) in the early stages of VM formation. Data showed that after 48 h hypoxia and 12 h incubation on matrigel SKOV3 ovarian cancer cells undergo the formation of matrix-associated intercellular connections referred hereafter as 3D channels-like structures, which arose previous to the apparition of canonical tubular structures representative of VM. Comprehensive profiling of 754 mature miRNAs at the onset of hypoxia-induced 3D channels-like structures showed that 11 hypoxamiRs were modulated (FC>1.5; p < 0.05) in SKOV3 cells (9 downregulated and 2 upregulated). Bioinformatic analysis of the set of regulated miRNAs showed that they might impact cellular pathways related with tumorigenesis. Moreover, overall survival analysis in a cohort of ovarian cancer patients (n = 485) indicated that low miR-765, miR-193b, miR-148a and high miR-138 levels were associated with worst patients outcome. In particular, miR-765 was severely downregulated after hypoxia (FC < 32.02; p < 0.05), and predicted to target a number of protein-encoding genes involved in angiogenesis and VM. Functional assays showed that ectopic restoration of miR-765 in SKOV3 cells resulted in a significant inhibition of hypoxia-induced 3D channels-like formation that was associated with a reduced number of branch points and patterned tubular-like structures. Mechanistic studies confirmed that miR-765 decreased the levels of VEGFA, AKT1 and SRC-α transducers and exerted a negative regulation of VEGFA by specific binding to its 3‘UTR. Finally, overall survival analysis of a cohort of ovarian cancer patients (n = 1435) indicates that high levels of VEGFA, AKT1 and SRC-α and low miR-765 expression were associated with worst patients outcome. In conclusion, here we reported a novel hypoxamiRs signature which constitutes a molecular guide for further clinical and functional studies on the early stages of VM. Our data also suggested that miR-765 coordinates the formation of 3D channels-like structures through modulation of VEGFA/AKT1/SRC-α axis in SKOV3 ovarian cancer cells

International lower limb collaborative (INTELLECT) study: a multicentre, international retrospective audit of lower extremity open fractures

Trauma remains a major cause of mortality and disability across the world1, with a higher burden in developing nations2. Open lower extremity injuries are devastating events from a physical3, mental health4, and socioeconomic5 standpoint. The potential sequelae, including risk of chronic infection and amputation, can lead to delayed recovery and major disability6. This international study aimed to describe global disparities, timely intervention, guideline-directed care, and economic aspects of open lower limb injuries

The CARMENES search for exoplanets around M dwarfs HD147379 b: A nearby Neptune in the temperate zone of an early-M dwarf

We report on the first star discovered to host a planet detected by radial velocity (RV) observations obtained within the CARMENES survey for exoplanets around M dwarfs. HD 147379 (V = 8.9 mag, M = 0.58 ± 0.08 M⊙), a bright M0.0 V star at a distance of 10.7 pc, is found to undergo periodic RV variations with a semi-amplitude of K = 5.1 ± 0.4 m s−1 and a period of P = 86.54 ± 0.06 d. The RV signal is found in our CARMENES data, which were taken between 2016 and 2017, and is supported by HIRES/Keck observations that were obtained since 2000. The RV variations are interpreted as resulting from a planet of minimum mass mP sin i = 25 ± 2 M⊕, 1.5 times the mass of Neptune, with an orbital semi-major axis a = 0.32 au and low eccentricity (e < 0.13). HD 147379 b is orbiting inside the temperate zone around the star, where water could exist in liquid form. The RV time-series and various spectroscopic indicators show additional hints of variations at an approximate period of 21.1 d (and its first harmonic), which we attribute to the rotation period of the star.FEDER/ERF FICTS-2011-02 fundsMajor Research Instrumentation Programme and DFG Research Unit FOR2544 “Blue Planets around Red StarsEuropean Research Council (ERC-279347), Deutsche Forschungsgemeinschaft (RE 1664/12-1, RE 2694/4-1), Bundesministerium für Bildung und Forschung (BMBF-05A14MG3, BMBF-05A17MG3), Spanish Ministry of Economy and Competitiveness (MINECO, grants AYA2015-68012-C2-2-P, AYA2016-79425-C3-1,2,3-P, AYA2015-69350-C3-2-P, AYA2014-54348-C03- 01, AYA2014-56359-P, AYA2014-54348-C3-2-R, AYA2016-79425-C3-3-P and 2013 Ramòn y Cajal program RYC-2013-14875), Fondo Europeo de Desarrollo Regional (FEDER, grant ESP2016-80435-C2-1-R, ESP2015-65712-C5- 5-R), Generalitat de Catalunya/CERCA programme, Spanish Ministerio de Educación, Cultura y Deporte, programa de Formación de Profesorado Universitario (grant FPU15/01476), Deutsches Zentrum für Luft- und Raumfahrt (grants 50OW0204 and 50OO1501), Office of Naval Research Global (award no. N62909-15-1-2011), Mexican CONACyT grant CB-2012-183007

ECM deposition is driven by caveolin-1-dependent regulation of exosomal biogenesis and cargo sorting

© 2020 Albacete-Albacete et al.The composition and physical properties of the extracellular matrix (ECM) critically influence tumor progression, but the molecular mechanisms underlying ECM layering are poorly understood. Tumor–stroma interaction critically depends on cell communication mediated by exosomes, small vesicles generated within multivesicular bodies (MVBs). We show that caveolin-1 (Cav1) centrally regulates exosome biogenesis and exosomal protein cargo sorting through the control of cholesterol content at the endosomal compartment/MVBs. Quantitative proteomics profiling revealed that Cav1 is required for exosomal sorting of ECM protein cargo subsets, including Tenascin-C (TnC), and for fibroblast-derived exosomes to efficiently deposit ECM and promote tumor invasion. Cav1-driven exosomal ECM deposition not only promotes local stromal remodeling but also the generation of distant ECM-enriched stromal niches in vivo. Cav1 acts as a cholesterol rheostat in MVBs, determining sorting of ECM components into specific exosome pools and thus ECM deposition. This supports a model by which Cav1 is a central regulatory hub for tumor–stroma interactions through a novel exosome-dependent ECM deposition mechanism.This study was supported by grants to M.A.d.P. from the Ministerio de Ciencia, Innovación y Universidades (MICINN: SAF2011- 25047, CSD2009-0016, SAF2014-51876-R, SAF2017-83130-, the Fundació La Marató de TV3 (674/C/2013), the Worldwide Cancer Research Foundation (AICR 15-0404) and Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa”. M.A.d.P´s group received funding from the European Union Horizon 2020 research and innovation programme under Marie Sklodowska-Curie grant agreement nº 641639. J. B. was supported by MICINN grants SAF2013-48201-R and SAF2016-80883-R, and G. O. was supported by INSERM, the University of Strasbourg, the Ligue contre le Cancer, and the Institut National du Cancer (INCa). LA-A was supported by a MICINN predoctoral fellowship associated with the Severo Ochoa Excellence program (FPI). IN-L was supported by a postdoctoral fellowship from the Asociación Española Contra el Cáncer (AECC). Miguel Sánchez Álvarez (CNIC) provided help with the manuscript preparation. Simon Bartlett (CNIC) provided English editing. The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505

Dar apoyo y supervisión en el mejoramiento de la medición en infraestructura hidroagrícola: obras de toma de presas de almacenamiento y canales de los distritos de riego: 004 Don Martín, N.L., 005 Delicias, Chih., 006 Palestina, Coah., 010 Culiacán-Humaya, Sin., 011 Alto Río Lerma, Gto., 013 estado de Jalisco, 014 Río Colorado, B.C., 017 Región Lagunera, Coah-Dgo., 020 Morelia-Queréndaro, Mich., 025 Bajo Río Bravo, Tamps., 026 Bajo Río San Juan, Tamps., 030 Valsequillo, Pue., 034 estado de Zacatecas, 037 Altar-Pitiquito-Caborca, Son., 038 Río Mayo, Son., 041 Río Yaqui, Son., 042 Buenaventura, Chih., 045 Tuxpan, Mich., 052 estado de Durango, 057 Amuco-Cutzamala, Gro., 063 Guasave, Sin., 074 Mocorito, Sin., 075 Río Fuerte, Sin., 076 Valle del Carrizo, Sin., 083 Papigochic, Chih., 085 La Begoña, Gto., 087 Rosario Mezquite, Mich., 089 El Carmen, Chih., 090 Bajo Río Conchos, Chih., 092b Río Pánuco-u. Pujal Coy, S.L.P., 093 Tomatlán, Jal, 094 Jalisco Sur, 097 Lázaro Cárdenas, Mich., 103 Río Florido, Chih., 105 Nexpa, Gro., 108 Elota-Piaxtla, Sin., 109 Río San Lorenzo, Sin., y 111 Baluarte-Presidio, Sin.

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Planeación y desarrollo de tecnología. Visiones sustentables de la vivienda y la transformación urbana

La urbanización es un proceso imparable. Para 2050 la ONU calcula que 70% de las 9,700 millones de personas que habitarán la Tierra lo hará en zonas urbanas. Los retos que impone este fenómeno son de enormes proporciones, en especial para conformar una ciudad incluyente, diversa y sustentable. Este volumen se enfoca en el problema de la vivienda urbana con el fin de aportar opciones para el desarrollo de proyectos sustentables. A partir del análisis de la producción habitacional actual y de fenómenos como la transformación del paisaje metropolitano y la pérdida de los ecosistemas fluviales, se presentan líneas de trabajo que van desde la construcción de un marco conceptual para evaluar la sustentabilidad en proyectos de vivienda, hasta alternativas para abatir el rezago habitacional y para la construcción de viviendas resilientes. Además, se ofrecen iniciativas de tecnología habitacional para el consumo sostenible en el espacio doméstico, el uso eficiente de la energía eléctrica, y un ejemplo de acompañamiento para la construcción y operación de un proyecto comunitario. Obra dirigida a estudiantes, académicos, investigadores y todo interesado en el tema de la sustentabilidad y el desarrollo de un mejor entorno para vivir

Aportes a la sustentabilidad. Una mirada desde la gestión del territorio y los recursos naturales

Este libro es el resultado de un ejercicio académico de colaboración que tiene como finalidad vincular aportaciones teóricas, reflexiones de caso y proyectos específicos que contribuyen en la búsqueda de alternativas a problemas abordados desde la sustentabilidad, considerando una gran variedad de perspectivas y enfoques disciplinares. Es una publicación colectiva que busca atraer la atención de los interesados en las disciplinas urbanas y del medio ambiente construido, las ciencias ambientales y todas aquellas cuyo objeto de estudio y metodologías de abordaje consideren trasversalmente la visión amplia de la sustentabilidad tanto en la gestión del territorio como en la eficiencia de los recursos naturales.Consejo Estatal de Ciencia y Tecnología de Jalisc