Aproximación bibliográfica a Alonso Cano y su escuela

AA. VV. Escultura religiosa granadina: desde la reconquista hasta Alonso Cano: exposicion celebrada en Granada en las fiestas del Santísimo Corpus Christi, mayo-junio 1940: catálogo de la exposición. Granada: Imp. Urania, 1940.AA. VV. Catálogo de la exposición de Siete obras maestras del arte español del s. XVIl.· Velázquez, Zurbarán, Alonso Cano, Pedro de Mena, de colecciones barcelonesas: celebrada en la Sala París-Barcelona, diciembre-enero 1949-1950. Barcelona: Edimar, 1949.AA. VV. Pintores granadinos del siglo XVIl. Actos conmemorativos del Tricentenario de Bartolomé E. Murillo. Sevilla: Ministerio de Cultura-Dirección de Bellas Artes y Archivos, 1982

Costos de la licencia de maternidad para apoyar la lactancia materna en Brasil, Ghana y México

Objective To develop a method to assess the cost of extending the duration of maternity leave for formally-employed women at the national level and apply it in Brazil, Ghana and Mexico. Methods We adapted a World Bank costing method into a five-step method to estimate the costs of extending the length of maternity leave mandates. Our method used the unit cost of maternity leave based on working women’s weekly wages; the number of additional weeks of maternity leave to be analysed for a given year; and the weighted population of women of reproductive and legal working age in a given country in that year. We weighted the population by the probability of having a baby that year among women in formal employment, according to individual characteristics. We applied nationally representative cross-sectional data from fertility, employment and population surveys to estimate the costs of maternity leave for mothers employed in the formal sector in Brazil, Ghana and Mexico for periods from 12 weeks up to 26 weeks, the WHO target for exclusive breastfeeding. Findings We estimated that 640 742 women in Brazil, 33 869 in Ghana and 288 655 in Mexico would require formal maternity leave annually. The median weekly cost of extending maternity leave for formally working women was purchasing power parity international dollars (PPP$) 195.07 per woman in Brazil, PPP$ 109.68 in Ghana and PPP$ 168.83 in Mexico. Conclusion Our costing method could facilitate evidence-based policy decisions across countries to improve maternity protection benefits and support breastfeeding

CDH1 somatic alterations in Mexican patients with diffuse and mixed sporadic gastric cancer

Background: Diffuse gastric cancer (DGC) is associated with the reduction or absence of the expression of the cell adhesion protein E-cadherin (encoded by the CDH1 gene). Molecular characteristics are less well described for mixed gastric cancer (MGC). The main somatic alterations that have been described in the CDH1 gene are mutations, loss of heterozygosity (LOH) and promoter methylation. The aim was to analyze CDH1 somatic alterations in Mexican patients with diffuse and mixed gastric cancer. Methods: We searched for mutations in the CDH1 gene in tumor DNA from DGC (n = 13) and MGC (n = 7) patients by next generation sequencing (NGS). Validation of findings was performed using Sanger sequencing. LOH was analyzed using dinucleotide repeat markers surrounding the CDH1 gene, and methylation was investigated by DNA bisulfite conversion and sequencing. E-cadherin protein deficiency was analyzed by immunohistochemistry. Results: Seventeen point variants were identified by NGS, 13 of them were validated by Sanger sequencing. Only 1/13 had not been previously reported (c.-137C > A), and 12/13 were already reported as polymorphisms. Two DGC cases presented LOH at the locus 16q22.1 (13.3%). CDH1 promoter methylation was positive in (7/11) 63.6% and (4/6) 66.6% of the cases with DGC and MGC, respectively. E-cadherin protein deficiency was observed in 58.3% of DGC cases while 100% in MGC cases. Conclusions: While no pathogenic somatic mutations were found that could explain the diffuse histology of gastric cancer in DGC and MGC, methylation was the most common somatic inactivation event of the CDH1 gene, and LOH was rare. The previously unreported c.-137C > A variant modify the CDH1 gene expression since it alters the binding sites for transcription factors.This work was supported by the “Consejo Nacional de Ciencia y Tecnología (CONACYT)” (grant Ciencia Básica 2013–1-222972) and by the “Fondo de Investigación en Salud (FIS), Instituto Mexicano del Seguro Social (IMSS)” (grant FIS/IMSS/PROT/G13/1189), that contributed to the design of the study, collection, analysis, interpretation of data and writing the manuscript. We thank the following institutions: 1) Coordinación de Investigación en Salud (CIS), Instituto Mexicano del Seguro Social (IMSS) for the support given to ARBC, through the Professional Development in the International Research of Graduate Students (PRODESI) program; 2) Fundación IMSS, A.C. for the research grant awarded to JYSL and MTMT; 3) FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT/ Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274); 4) The project NORTE-01-0145-FEDER-000029, supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); 5) FCT fellowships (SFRH/BPD/86543/2012 to JC; SFRH/BPD/89764/2012 to PO; PD/ BD/128007/2016 to AS). IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT, the Portuguese Foundation for Science and Technology

Relación entre la respiración del suelo y propiedades indicadoras de la calidad del suelo en un viñedo de la D.O.Ca. Rioja con manejos alternativos

11 páginas, 6 figuras, 2 tablas.-- Trabajo presentado al IV Congreso Ibérico de la Ciencia del Suelo: "Suelo: Funciones y Manejo" celebrado en Granada del 21 al 24 de septiembre de 2010.En un suelo de viñedo representativo de la D.O.Ca Rioja se han estudiado la capacidad de dos manejos de suelo alternativos, cubiertas vegetales y la aplicación de sustrato de postcultivo de champiñón (SPCH) para incrementar el carbono orgánico del suelo y mejorar la calidad del mismo. Se muestreó la capa más superficial del suelo (0-5 cm), y se encontró que ambos manejos incrementaron la materia orgánica total y las hcciones lábiles como el Carbono soluble y el Nitrógeno potencialmente mineralizable. Sin embargo las cubiertas vegetales presentan mayor actividad enzimática B-Glucosidasa y Ureasa; las cuales mostraron altas correlaciones con la respiración del suelo.El presente trabajo se realizado gracias al INIA y el Fondo Social Europeo a través del programa de Doctores INIA-CCAA. También gracias a la financiación del Gobierno de la Rioja a través del proyecto regional R-07-09 y del INIA (proyecto RTA 2009-00101-00-00).Peer reviewe

The use of fluoroproline in MUC1 antigen enables efficient detection of antibodies in patients with prostate cancer

A structure-based design of a new generation of tumor-associated glycopeptides with improved affinity against two anti-MUC1 antibodies is described. These unique antigens feature a fluorinated proline residue, such as a (4S)-4-fluoro-l-proline or 4,4-difluoro-l-proline, at the most immunogenic domain. Binding assays using biolayer interferometry reveal 3-fold to 10-fold affinity improvement with respect to the natural (glyco)peptides. According to X-ray crystallography and MD simulations, the fluorinated residues stabilize the antigen-antibody complex by enhancing key CH/π interactions. Interestingly, a notable improvement in detection of cancer-associated anti-MUC1 antibodies from serum of patients with prostate cancer is achieved with the non-natural antigens, which proves that these derivatives can be considered better diagnostic tools than the natural antigen for prostate cancer.We thank the Ministerio de Economía y Competitividad (projects CTQ2015-67727-R, UNLR13-4E-1931, CTQ2013-44367-C2-2-P, CTQ2015-64597-C2-1P, and BFU2016-75633-P). I.A.B. thanks the Asociación Española Contra el Cancer en La Rioja for a grant. I.S.A. and G.J.L.B. thank FCT Portugal (Ph.D. studentship and FCT Investigator, respectively) and EPSRC. G.J.L.B. holds a Royal Society URF and an ERC StG (TagIt). F.C. and G.J.L.B thank the EU (Marie-Sklodowska Curie ITN, Protein Conjugates). R.H-G. thanks Agencia Aragonesa para la Investigación y Desarrollo (ARAID) and the Diputación General de Aragón (DGA, B89) for financial support. The research leading to these results has also received funding from the FP7 (2007-2013) under BioStruct-X (grant agreement no. 283570 and BIOSTRUCTX_5186). We thank synchrotron radiation source DIAMOND (Oxford) and beamline I04 (number of experiment mx10121-19). The Hokkaido University group acknowledges JSPS KAKENHI grant no. 25220206 and JSPS Wakate B KAKENHI grant no. 24710242. We also thank CESGA (Santiago de Compostela) for computer support.Peer reviewedPeer Reviewe

Structure-Guided Approach for the Development of MUC1-Glycopeptide-Based Cancer Vaccines with Predictable Responses

Mucin-1 (MUC1) glycopeptides are exceptional candidates for potential cancer vaccines. However, their autoantigenic nature often results in a weak immune response. To overcome this drawback, we carefully engineered synthetic antigens with precise chemical modifications. To be effective and stimulate an anti-MUC1 response, artificial antigens must mimic the conformational dynamics of natural antigens in solution and have an equivalent or higher binding affinity to anti-MUC1 antibodies than their natural counterparts. As a proof of concept, we have developed a glycopeptide that contains noncanonical amino acid (2S,3R)-3-hydroxynorvaline. The unnatural antigen fulfills these two properties and effectively mimics the threonine-derived antigen. On the one hand, conformational analysis in water shows that this surrogate explores a landscape similar to that of the natural variant. On the other hand, the presence of an additional methylene group in the side chain of this analog compared to the threonine residue enhances a CH/π interaction in the antigen/antibody complex. Despite an enthalpy–entropy balance, this synthetic glycopeptide has a binding affinity slightly higher than that of its natural counterpart. When conjugated with gold nanoparticles, the vaccine candidate stimulates the formation of specific anti-MUC1 IgG antibodies in mice and shows efficacy comparable to that of the natural derivative. The antibodies also exhibit cross-reactivity to selectively target, for example, human breast cancer cells. This investigation relied on numerous analytical (e.g., NMR spectroscopy and X-ray crystallography) and biophysical techniques and molecular dynamics simulations to characterize the antigen–antibody interactions. This workflow streamlines the synthetic process, saves time, and reduces the need for extensive, animal-intensive immunization procedures. These advances underscore the promise of structure-based rational design in the advance of cancer vaccine development

Prognostic Impact of Nutritional Status After Transcatheter Edge-to-Edge Mitral Valve Repair: The MIVNUT Registry

Background Malnutrition is associated with poor prognosis in several cardiovascular diseases. However, its prognostic impact in patients undergoing transcatheter edge-to-edge mitral valve repair (TEER) is not well known. This study sought to assess the prevalence, clinical associations, and prognostic consequences of malnutrition in patients undergoing TEER. Methods and Results A total of 892 patients undergoing TEER from the international MIVNUT (Mitral Valve Repair and Nutritional Status) registry were studied. Malnutrition status was assessed with the Controlling Nutritional Status score. The association of nutritional status with mortality was analyzed with multivariable Cox regression models, whereas the association with heart failure admission was assessed by Fine-Gray models, with death as a competing risk. According to the Controlling Nutritional Status score, 74.4% of patients with TEER had any degree of malnutrition at the time of TEER (75.1% in patients with body mass index <25?kg/m2, 72.1% in those with body mass index ?25?kg/m2). However, only 20% had moderate-severe malnutrition. TEER was successful in most of patients (94.2%). During a median follow-up of 1.6?years (interquartile range, 0.6-3.0), 267 (29.9%) patients died and 256 patients (28.7%) were admitted for heart failure after TEER. Compared with normal nutritional status moderate-severe malnutrition resulted a strong predictor of mortality (adjusted hazard ratio [HR], 2.1 [95% CI, 1.1-2.4]; P<0.001) and heart failure admission (adjusted subdistribution HR, 1.6 [95% CI, 1.1-2.4]; P=0.015). Conclusions Malnutrition is common among patients submitted to TEER, and moderate-severe malnutrition is strongly associated with increased mortality and heart failure readmission. Assessment of nutritional status in these patients may help to improve risk stratification

Bioorthogonal Self-Immolative Linker Based on Grob Fragmentation

A self-immolative bioorthogonal conditionally cleavable linker based on Grob fragmentation is described. It is derived from 1,3-aminocyclohexanols and allows the release of sulfonate-containing compounds in aqueous media. Modulation of the amine pKa promotes fragmentation even at slightly acidic pH, a common feature of several tumor environments. The Grob fragmentation can also occur under physiological conditions in living cells, highlighting the potential bioorthogonal applicability of this reaction.We thank the Agencia Estatal de Investigación of Spain (AEI; Grant No. RTI2018-099592−B-C21). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 675007. M.S.-C. thanks the Asociación Española Contra el Cáncer AECC (La Rioja) for the predoctoral fellowship. E.J.-M. acknowledges the contract Beatriz Galindo from the Ministry of Universities of Spain.Peer reviewe