Comparative study of the antitumoral activity of phosphine- thiosemicarbazone gold(I) complexes obtained by different methodologies

A series of phosphino-thiosemicarbazone gold(I) dinuclear complexes obtained by two different synthetic pro- cedures have been prepared. All the compounds have been spectroscopically characterized including single crystal X ray diffraction analysis in some of cases. [Au2(HL1)Cl2] (1), [Au2(HL2)2]Cl2 (2) and [Au2(HL3)2]Cl2 (3) have been prepared by chemical synthesis using a gold(III) salt as precursor; while [Au2(L1)2] (4), [Au2(L2)2] ∙2CH3CN (5) and [Au2(L3)2] (6) have been isolated from an electrochemical synthesis (HLn=2-[2-(diphenyl- phosphanyl)-benzylidene]-N-R-thiosemicarbazone; HL1: R=methyl, HL2: R=methoxyphenyl, HL3: R=nitrophenyl). The in vitro cytotoxic activity of these gold(I) complexes was tested against some human tumor cell lines: HeLa 229 (cervical epithelial carcinoma), MCF-7 (ovarian adenocarcinoma), NCI-H460 (non- small-cell lung cancer) and MRC5 (normal human lung fibroblast), and the IC50 values compared with those of cisplatin. The neutral methyl-substituted complexes 1 and 4 and methoxyphenyl 5 displayed significant cyto- toxic activities in all investigated cancer cell lines, being 1 and 4 the most effective. The ability of complexes 1 and 4 to induce cell death by apoptosis in Hela 229 was also investigated by fluorescence microscopy using the apoptotic DNA fragmentation as marker. These results indicated that the inhibition of cell proliferation is mainly due to an apoptotic process. In order to obtain more information about the mechanism of action of these me- tallocompounds, the interactions of complexes 1 and 4 with the thioredoxin reductase (TrxR) enzyme were analyzed. Both complexes exhibited a strong inhibition of the thioredoxin reductase activity.We thank Xunta de Galicia (ED431C 2018/13 and ED431D 2017/01), MINECO (CTQ2017-90802-REDT) and Ministerio de Ciencia, Innovación y Universidades (RED2018-102471-T) for financial support. L. M. G. B. thanks Xunta de Galicia for the predoctoral contract (type A).S

Slavery and the african cultural legacy in the Caribbean

Con autorización de la editorial para este libro.[EN] The purpose of this book is to raise awareness among a wide audience of one of the most significant and shameful phenomena for humanity, as was the enslavement of over twelve and a half million Africans who were brought to America and forced to work and live as slaves. Many countries participated in the slave trade at different times and withvaried intensity (Great Britain, Portugal, France, Spain, Denmark, Netherlands, Germany, United States...).[ES] El propósito de esta obra es dar a conocer a un público amplio uno de los fenómenos de mayor trascendencia y vergüenza para la humanidad como fue la esclavización de más de doce millones y medio de africanos que fueron trasladados a América, obligados a trabajar y vivir como esclavos. Muchos países participaron en la trata de esclavos en distintos momentos y con diferente intensidad (Gran Bretaña, Portugal, Francia, España, Dinamarca, Países Bajos, Alemania, Estados Unidos…).Connected Worlds: The Caribbean, Origin of Modern World. This project has received funding from the European Union´s Horizon 2020 research and innovation programme under the Marie Sklodowska Curie grant agreement Nº 823846. This project is directed by professor Consuelo Naranjo Orovio, Institute of History-CSIC.Peer reviewe

Blueprint for a minimal photoautotrophic cell: conserved and variable genes in Synechococcus elongatus PCC 7942

Background: Simpler biological systems should be easier to understand and to engineer towards pre-defined goals. One way to achieve biological simplicity is through genome minimization. Here we looked for genomic islands in the fresh water cyanobacteria Synechococcus elongatus PCC 7942 (genome size 2.7 Mb) that could be used as targets for deletion. We also looked for conserved genes that might be essential for cell survival.Results: By using a combination of methods we identified 170 xenologs, 136 ORFans and 1401 core genes in the genome of S. elongatus PCC 7942. These represent 6.5%, 5.2% and 53.6% of the annotated genes respectively. We considered that genes in genomic islands could be found if they showed a combination of: a) unusual G+C content; b) unusual phylogenetic similarity; and/or c) a small number of the highly iterated palindrome 1 (HIP1) motif plus an unusual codon usage. The origin of the largest genomic island by horizontal gene transfer (HGT) could be corroborated by lack of coverage among metagenomic sequences from a fresh water microbialite. Evidence is also presented that xenologous genes tend to cluster in operons. Interestingly, most genes coding for proteins with a diguanylate cyclase domain are predicted to be xenologs, suggesting a role for horizontal gene transfer in the evolution of Synechococcus sensory systems.Conclusions: Our estimates of genomic islands in PCC 7942 are larger than those predicted by other published methods like SIGI-HMM. Our results set a guide to non-essential genes in S. elongatus PCC 7942 indicating a path towards the engineering of a model photoautotrophic bacterial cell.Financial support was provided by grants BFU2009-12895-C02-01/BMC (Ministerio de Ciencia e Innovación, Spain), the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement number 212894 and Prometeo/2009/092 (Conselleria d’Educació, Generalitat Valenciana, Spain) to A. Moya. Work in the FdlC laboratory was supported by grants BFU2008-00995/BMC (Spanish Ministry of Education), RD06/0008/1012 (RETICS research network, Instituto de Salud Carlos III, Spanish Ministry of Health) and LSHM-CT- 2005_019023 (European VI Framework Program). Dr. González-Domenech was supported by grant from the University of Granada. LD, thanks to financial support from Facultad de Ciencias, Universidad Nacional Autónoma de México

Conjugative transfer can be inhibited by blocking relaxase activity within recipient cells with intrabodies

Horizontal transfer of antibiotic resistance genes carried by conjugative plasmids poses a serious health problem. As conjugative relaxases are transported to recipient cells during bacterial conjugation, we investigated whether blocking relaxase activity in the recipient cell might inhibit conjugation. For that purpose, we used an intrabody approach generating a single-chain Fv antibody library against the relaxase TrwC of conjugative plasmid R388. Recombinant single-chain Fv antibodies were engineered for cytoplasmic expression in Escherichia coli cells and either selected in vitro for their specific binding to TrwC, or in vivo by their ability to interfere with conjugation using a high-throughput mating assay. Several intrabody clones were identified showing specific inhibition against R388 conjugation upon cytoplasmic expression in the recipient cell. The epitope recognized by one of these intrabodies was mapped to a region of TrwC containing Tyr-26 and involved in the conjugative DNA-processing termination reaction. These findings demonstrate that the transferred relaxase plays an important role in the recipient cell and open a new approach to identify specific inhibitors of bacterial conjugation. © 2006 The Authors.This work was supported by Grants BFU2005-03477/BMC (Spanish Ministry of Education) and LSHM-CT-2005-019023 (European VI Framework Program) to F.C and Grants BIO2005-03964 (Spanish Ministry of Education) and LSHBCT-2005-512061 (European VI Framework Program) to L.A.F. M.P.G.-B. is a postdoctoral scientist supported by a fellowship from Fundación Marqués de Valdecilla, and later by Grant LSHM-CT-2005-019023. B.G.-P. and P.J. are recipients of PhD fellowships from Spanish Ministry of Education. G.M. is a Ramón y Cajal Research Associate.Peer Reviewe

Conversion of a double-tetranuclear cluster silver helicate into a dihelicate via a rare desulfurization process

We present the first example of a silver double-tetranuclear cluster helicate [Ag4L2]2 obtained from a bisthiosemicarbazone ligand using electrochemical synthesis. This cluster helicate undergoes a rare desulfurization process in chloroform giving rise to a cationic silver dihelicate [Ag2(H2L)2]SO4. This is the first silver mediated desulfurization reaction.FEDER cofunded-grants: from Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia, 2017 GRC GI-1682 (ED431C 2017/01), 2018 GRC GI-1584 (ED431C 2018/13), MetalBIO Network (ED431D 2017/01), Ministerio de Ciencia, Innovación y Universidades, METALBIO (CTQ2017-90802-REDT) and MultiMetDrugs (RED2018-102471-T)

Consuelo Naranjo Orovio; Miguel Ángel Puig-Samper (edición y guión). La esclavitud y el legado cultural de África en el Caribe. Documental

DocumentalPeer reviewe

Glioblastoma: does the pre-treatment geometry matter? A postcontrast T1 MRI-based study.

BACKGROUND The potential of a tumour's volumetric measures obtained from pretreatment MRI sequences of glioblastoma (GBM) patients as predictors of clinical outcome has been controversial. Mathematical models of GBM growth have suggested a relation between a tumour's geometry and its aggressiveness. METHODS A multicenter retrospective clinical study was designed to study volumetric and geometrical measures on pretreatment postcontrast T1 MRIs of 117 GBM patients. Clinical variables were collected, tumours segmented, and measures computed including: contrast enhancing (CE), necrotic, and total volumes; maximal tumour diameter; equivalent spherical CE width and several geometric measures of the CE "rim". The significance of the measures was studied using proportional hazards analysis and Kaplan-Meier curves. RESULTS Kaplan-Meier and univariate Cox survival analysis showed that total volume [p = 0.034, Hazard ratio (HR) = 1.574], CE volume (p = 0.017, HR = 1.659), spherical rim width (p = 0.007, HR = 1.749), and geometric heterogeneity (p = 0.015, HR = 1.646) were significant parameters in terms of overall survival (OS). Multivariable Cox analysis for OS provided the later two parameters as age-adjusted predictors of OS (p = 0.043, HR = 1.536 and p = 0.032, HR = 1.570, respectively). CONCLUSION Patients with tumours having small geometric heterogeneity and/or spherical rim widths had significantly better prognosis. These novel imaging biomarkers have a strong individual and combined prognostic value for GBM patients. KEY POINTS • Three-dimensional segmentation on magnetic resonance images allows the study of geometric measures. • Patients with small width of contrast enhancing areas have better prognosis. • The irregularity of contrast enhancing areas predicts survival in glioblastoma patients