Quantization of Weyl invariant unimodular gravity with antisymmetric ghost fields

The enforcement of the unimodularity condition in a gravity theory by means of a Lagrange multiplier leads, in general, to inconsistencies upon quantization. This is so, in particular, when the classic linear splitting of the metric between the background and quantum fields is used. To avoid the need of introducing such a Lagrange multiplier while using the classic linear splitting, we carry out the quantization of unimodular gravity with extra Weyl symmetry by using Becchi-Rouet-Stora-Tyutin (BRST) techniques. Here, two gauge symmetries are to be gauge-fixed: transverse diffeomorphisms and Weyl transformations. We perform the gauge-fixing of the transverse diffeomorphism invariance by using BRST transformations that involve antisymmetric ghost fields. We show that these BRST transformations are compatible with the BRST transformations needed to gauge-fix the Weyl symmetry, so that they can be combined in a set of transformations generated by a single BRST operator. Newton's law of gravitation is derived within the BRST formalism we put forward as well as the Slavnov-Taylor equation.Comment: 24 pages, 1 table, 1 figur

The Role of the TGF-beta Coreceptor Endoglin in Cancer

Endoglin (CD105) is an auxiliary membrane receptor of transforming growth factor beta (TGF-beta) that interacts with type I and type II TGF-beta receptors and modulates TGF-beta signaling. Endoglin is overexpressed in the tumor-associated vascular endothelium, where it modulates angiogenesis. This feature makes endoglin a promising target for antiangiogenic cancer therapy. In addition, recent studies on human and experimental models of carcinogenesis point to an important tumor cell-autonomous role of endoglin by regulating proliferation, migration, invasion, and metastasis. These studies suggest that endoglin behaves as a suppressor of malignancy in experimental and human epithelial carcinogenesis, although it can also promote metastasis in other types of cancer. In this review, we evaluate the implication of endoglin in tumor development underlying studies developed in our laboratories in recent years

From the smallest to the largest subcellular plant pathogen: Citrus tristeza virus and its unique p23 protein

Knowledge on diseases caused by Citrus tristeza virus (CTV) has greatly increased in last decades after their etiology was demonstrated in the past seventies. Professor Ricardo Flores substantially contributed to these advances in topics like: I) improvement of virus purification to obtain biologically active virions, II) sequencing mild CTV isolates for genetic comparisons with sequences of moderate or severe isolates and genetic engineering, III) analysis of genetic variation of both CTV genomic RNA ends and features of the highly variable 5′ end that allow accommodating this variation within a conserved secondary structure, IV) studies on the structure, subcellular localization and biological functions of the CTV-unique p23 protein, and v) potential use of p23 and other 3′ -proximal regions of the CTV genome to develop transgenic citrus resistant to the virus. Here we review his main achievements on these topics and how they contributed to deeper understanding of CTV biology and to new potential measures for disease control

Metal-Organic-Framework-based nanofiltration membranes for selective multi-cationic recovery from seawater and brines

Nanofiltration (NF) is gaining a role of increasing importance in Zero Liquid Discharge (ZLD)/Minimal Liquid Discharge (MLD) systems, enhancing the efficiency of downstream technologies to recover valuable minerals from seawater and brines. However, often the purity of the recovered minerals does not meet market specifications, making ZLD/MLD currently economically unfeasible. To such end, in this study, a novel positively charged NF membrane was developed to enhance magnesium and calcium selectivity. The membrane comprised: (i) an ultrafiltration substrate and (ii) an active layer that incorporated NH2-MIL-101(Al) and ZnO nanoparticles in a chitosan matrix. The influence of different loadings of NH2-MIL-101(Al) and ZnO on membrane structure, selectivity and water permeability was investigated. Initial filtration tests with single-salt solutions at 1000 ppm (NaCl, Na2SO4, MgCl2, CaCl2) showed that the membrane with 35%wt of ZnO presented the highest rejections of MgCl2 (90.10%) and CaCl2 (86.49%). Selectivity towards MgCl2 and CaCl2 was higher than those of commercial membranes (NF90 and NF270) and the positively charged membranes introduced in recent literature. The novel synthesized membrane in this work was also tested with synthetic seawater and brine at a trans-membrane pressure of 30 bar. Results highlighted the intriguing competitiveness of the novel membrane in terms of magnesium and calcium selectivity with NF90 and NF270 within the field of both seawater and brine valorization.The authors would like to acknowledge that parts of the research activities were carried out within the framework of "Programma Operativo Nazionale Ricerca e Innovazione2014-2020 (CCI 2014IT16M2OP005), Fondo Sociale Europeo, Azione I.1 “Dottorati Innovativi con caratterizzazione Industriale”, Code: DOT204NJ79, CUP: B73D20005110001. J. López research was developed under the Margarita Salas postdoctoral fellowship from Ministerio de Universidades (MIU) and founded by the European Union-NextGenerationEU. Moreover, J.L. Cortina received support for the research through the “ICREA Academia” recognition for excellence in research funded by the Generalitat de Catalunya.Peer ReviewedPostprint (published version

Transgenic citrus plants expressing the citrus tristeza virus p23 protein exhibit viral-like symptoms

The 23 kDa protein (p23) coded by the 3'-terminal gene of Citrus tristeza virus (CTV), a member of the genus Closterovirus with the largest genome among plant RNA viruses, is an RNA-binding protein that contains a motif rich in cysteine and histidine residues in the core of a putative zinc-finger domain. On this basis, a regulatory role for CTV replication or gene expression has been suggested for p23. To explore whether over-expression of this protein in transgenic plants could affect the normal CTV infection process, transgenic Mexican lime plants were generated carrying the p23 transgene, or a truncated version thereof, under the control of the cauliflower mosaic virus (CaMV) 35S promoter. Constitutive expression of p23 induced phenotypic aberrations that resembled symptoms incited by CTV in non-transgenic lime plants, whereas transgenic plants expressing the p23 truncated version were normal. The onset of CTV-like symptoms in p23 transgenic plants was associated with the expression of p23, and its accumulation level paralleled the intensity of the symptoms. This demonstrates that p23 is involved in symptom development and that it most likely plays a key role in CTV pathogenesis. This is the first case in which a protein encoded by a woody plant-infecting RNA virus has been identified as being directly involved in pathogenesis in its natural host. This finding also delimits a small region of the large CTV genome for the future mapping of specific pathogenic determinants

Accumulation of transgene-derived siRNAs is not sufficient for RNAi-mediated protection against Citrus tristeza virus in transgenic Mexican lime

P>Mexican lime plants transformed with the 3'-terminal 549 nucleotides of the Citrus tristeza virus (CTV) genome in sense, antisense and intron-hairpin formats were analysed for transgene-derived transcript and short interfering RNA (siRNA) accumulation, and for CTV resistance. Propagations from all sense, antisense and empty-vector transgenic lines were susceptible to CTV, except for a single sense-line plant with a complex transgene integration pattern that showed transgene-derived siRNAs in association with low levels of the transgene-derived transcript. In contrast, nine of 30 intron-hairpin lines showed CTV resistance, with 9%-56% of bud-propagated plants, depending on the line, remaining uninfected on graft inoculation, and the others being susceptible. Although resistance was always associated with the presence of transgene-derived siRNAs, their level in different sense and intron-hairpin transformants was variable irrespective of the response to CTV infection. In intron-hairpin lines with single transgene integration, CTV resistance was correlated with low accumulation of the transgene-derived transcript rather than with high accumulation of transgene-derived siRNAs

El registro fósil de vertebrados y patrimonio paleontológico más representativo de los pirineos occidentales

Los Pirineos occidentales son un territorio con una notable diversidad geológica y un importante registro fósil, que constituye un gran archivo de paleobiodiversidad. En lo que respecta al registro fósil de vertebrados, los Pirineos occidentales (Región Vasco-Cantábrica, Cuenca de Pamplona y sector noroccidental de la Cuenca del Ebro) son relevantes tanto desde el punto de vista de los yacimientos paleontológicos como de las colecciones de fósiles procedentes de ellos. Varios yacimientos de vertebrados forman parte del Inventario de Lugares de Interés Geológico (LIG) con alto o muy alto interés paleontológico en la Comunidad Autónoma del País Vasco. Destacan los yacimientos de peces cretácicos de Zeanuri en Bizkaia, mamíferos eocenos de Zambrana e icnitas miocenas de Salinas de Añana en Álava/Araba y la asociación de vertebrados pleistocenos de Kiputz cerca de Mutriku, en Gipuzkoa. Otros yacimientos notables en el área de estudio deberían ser objeto de iniciativas de geoconservación: es el caso de la cantera de Laño (Condado de Treviño), con asociaciones fi nicretácicas de vertebrados continentales y marinos, los afloramientos con icnitas de aves y mamíferos del Eoceno al Mioceno inferior de Navarra/Nafarroa y la cueva vizcaína de Santa Isabel de Ranero (Pleistoceno), por citar únicamente los ejemplos más sobresalientes. Asimismo, existen colecciones de fósiles de vertebrados en los Pirineos occidentales que destacan por su elevado interés paleontológico, aunque algunos no provengan de LIG reconocidos. Estas colecciones están depositadas en diversos centros e instituciones de Bilbao, Irún, Leioa, Pamplona-Iruñea, y Vitoria-Gasteiz. La valoración de la paleobiodiversidad y el registro fósil es un paso importante para el conocimiento del patrimonio paleontológico de un territorio y la creación de fi guras de geoconservación (e.g., LIG, geosites). Sin embargo, la mera inclusión de los yacimientos paleontológicos en estas fi guras no garantiza su protección y conservación, ni la adecuada gestión de las colecciones de fósiles procedentes de ellos. Por lo tanto, es necesario diseñar estrategias de conservación transversales teniendo en cuenta las particularidades de cada yacimiento y/o colección. La divulgación científi ca y cultural del patrimonio paleontológico de un territorio, como el aquí estudiado, debe contar con una mayor colaboración entre los paleontólogos que han valorado los bienes paleontológicos y los técnicos que los gestionan. Para ello, es necesaria la disposición de partidas presupuestarias específicas que posibiliten el desarrollo de diferentes acciones encaminadas a la investigación, conservación y difusión social de este patrimonio.The western Pyrenees is a territory with a remarkable geodiversity and an important fossil record, which constitutes a large archive of palaeobiodiversity. With respect to the vertebrate fossil record, the western Pyrenees (Basque-Cantabrian Region, Pamplona Basin and the north-western sector of the Ebro Basin) are relevant both from the point of view of palaeontological sites and fossil collections. Several vertebrate fossil sites are integrated into the Inventory of Geological Interest Sites (LIG) with high to very high palaeontological interest of the Autonomous Community of the Basque Country. It is worth highlighting the Cretaceous fish sites of Zeanuri in Biscay, Eocene mammals of Zambrana and Miocene ichnites of Salinas de Añana in Araba, and the Pleistocene vertebrate fossil assemblage of Kiputz near Mutriku, in Gipuzkoa. Other highly significant sites in the study area should be subject to geoconservation initiatives. This is the case of the Laño quarry in the Condado de Treviño, which has provided continental and marine vertebrate fossil assemblages from the latest Cretaceous, Eocene to Early Miocene sites with bird and mammal tracks in Navarre, and the Pleistocene cave deposits of Santa Isabel de Ranero in Biscay, to mention only the most outstanding examples. There are also vertebrate fossil collections in the western Pyrenees that stand out for their high palaeontological interest, although some do not come from recognized LIG. These collections are deposited in several centres and institutions of Bilbao, Irun, Leioa, Pamplona-Iruñea and Vitoria-Gasteiz. The valuation of the palaeobiodiversity and fossil record is an important step for the study of palaeontological heritage of a territory and the set-up of geoconservation designations (e.g., LIG, geosites). However, the mere inclusion of the palaeontological assents in these geoconservation designations does not guarantee either their protection and conservation or the suitable management of the fossil collection. Therefore, it is necessary to design conservation strategies taking into account the particularities of each palaeontological site and/or fossil collection. The scientific and cultural dissemination of the palaeontological heritage of a territory like one studied here should have greater collaboration between the palaeontologists that have valued the palaeontological assets and the technicians and institutions that manage them. This requires the provision of specific budgetary items that enable the development of the different activities of research, conservation and social dissemination of this heritage.Fil: Badiola, Ainara. Universidad del País Vasco; EspañaFil: Arlegi, Mikel. Universidad del País Vasco; España. Université de Bordeaux; FranciaFil: Astibia, Humberto. Universidad del País Vasco; EspañaFil: Bardet, Nathalie. Centre National de la Recherche Scientifique; Francia. Muséum National d'Histoire Naturelle; Francia. Université Pierre et Marie Curie; FranciaFil: Berreteaga, Ana. Universidad del País Vasco; EspañaFil: Corral, J. Carmelo. Museo de Ciencias Naturales de Álava/; EspañaFil: Díaz Martínez, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; Argentina. Universidad Nacional de Río Negro. Sede Alto Valle. Instituto de Investigaciones en Paleobiología y Geología; ArgentinaFil: Gómez Olivencia, Asier. Universidad del País Vasco; España. IKERBASQUE. Basque Foundation for Science; España. Universidad Carlos III de Madrid. Instituto de Salud; EspañaFil: Lopez Horgue, Mikel A.. Universidad del País Vasco; EspañaFil: Perales Gogenola, Leire. Universidad del País Vasco; EspañaFil: Pereda Suberbiola, Xabier. Universidad del País Vasco; Españ

CD105 prevents apoptosis in hypoxic endothelial cells

CD105, a marker of endothelial cells, is abundantly expressed in tissues undergoing angiogenesis and is a receptor for transforming growth factorß. The pivotal role of CD105 in the vascular system was demonstrated by the severe vascular defects that occur in CD105-knockout mice, but the exact mechanisms for CD105 regulation of vascular development have not been fully elucidated. In light of the function of CD105 and the importance of hypoxia in neovascularisation, we speculated that CD105 is involved in hypoxia-initiated angiogenesis. Using tissue-cultured human microvascular endothelial cells, we have investigated the effects of hypoxic stress on CD105 gene expression. Hypoxia induced a significant increase in membrane-bound and secreted CD105 protein levels. CD105 mRNA and promoter activity were also markedly elevated, the latter returning to the basal level after 16 hours of hypoxic stress. Hypoxia induced cell cycle arrest at the G0/G1 phases and massive cell apoptosis after 24 hours through a reduction in the Bcl-2 to Bax ratio, downregulation of Bcl-XL and Mcl-1, and upregulation of caspase-3 and caspase-8. The consequence of CD105 upregulation was revealed using an antisense approach and a TUNEL assay. Suppression of CD105 increased cell apoptosis under hypoxic stress in the absence of TGFß1. Furthermore, hypoxia and TGFß1 synergistically induced apoptosis in the CD105-deficient cells but not in the control cells. We conclude that hypoxia is a potent stimulus for CD105 gene expression in vascular endothelial cells, which in turn attenuates cell apoptosis and thus contributes to angiogenesis