Genetically modified organisms for the environment: stories of success and failure and what we have learned from them

The expectations raised in the mid-1980s on the potential of genetic engineering for in situ remediation of environmental pollution have not been entirely fulfilled. Yet, we have learned a good deal about the expression of catabolic pathways by bacteria in their natural habitats, and how environmental conditions dictate the expression of desired catalytic activities. The many different choices between nutrients and responses to stresses form a network of transcriptional switches which, given the redundance and robustness of the regulatory circuits involved, can be neither unraveled through standard genetic analysis nor artificially programmed in a simple manner. Available data suggest that population dynamics and physiological control of catabolic gene expression prevail over any artificial attempt to engineer an optimal performance of the wanted catalytic activities. In this review, several valuable spin-offs of past research into genetically modified organisms with environmental applications are discussed, along with the impact of Systems Biology and Synthetic Biology in the future of environmental biotechnology. [Int Microbiol 2005; 8(3):213-222

CARGO: a web portal to integrate customized biological information

There is a huge quantity of information generated in Life Sciences, and it is dispersed in many databases and repositories. Despite the broad availability of the information, there is a great demand for methods that are able to look for, gather and display distributed data in a standardized and friendly way. CARGO (Cancer And Related Genes Online) is a configurable biological web portal designed as a tool to facilitate, integrate and visualize results from Internet resources, independently of their native format or access method. Through the use of small agents, called widgets, supported by a Rich Internet Application (RIA) paradigm based on AJAX, CARGO provides pieces of minimal, relevant and descriptive biological information. The tool is designed to be used by experimental biologists with no training in bioinformatics. In the current state, the system presents a list of human cancer genes. Available at http://cargo.bioinfo.cnio.e

Human prefoldin modulates co-transcriptional pre-mRNA splicing.

Prefoldin is a heterohexameric complex conserved from archaea to humans that plays a cochaperone role during the co-translational folding of actin and tubulin monomers. Additional functions of prefoldin have been described, including a positive contribution to transcription elongation and chromatin dynamics in yeast. Here we show that prefoldin perturbations provoked transcriptional alterations across the human genome. Severe pre-mRNA splicing defects were also detected, particularly after serum stimulation. We found impairment of co-transcriptional splicing during transcription elongation, which explains why the induction of long genes with a high number of introns was affected the most. We detected genome-wide prefoldin binding to transcribed genes and found that it correlated with the negative impact of prefoldin depletion on gene expression. Lack of prefoldin caused global decrease in Ser2 and Ser5 phosphorylation of the RNA polymerase II carboxy-terminal domain. It also reduced the recruitment of the CTD kinase CDK9 to transcribed genes, and the association of splicing factors PRP19 and U2AF65 to chromatin, which is known to depend on CTD phosphorylation. Altogether the reported results indicate that human prefoldin is able to act locally on the genome to modulate gene expression by influencing phosphorylation of elongating RNA polymerase II, and thereby regulating co-transcriptional splicing.Ministerio de Ciencia e Innovación-Agencia Estatal de Investigación [BFU2016-77728-C3-1-P to S.C. and BFU2017-85420-R to J.C.R.] co-financed with European Union funds (FEDER); Andalusian Government [P12-BIO1938MO, BIO271, US-1256285 to S.C., BIO321 to J.C.R.]; Junta de Andalucía (to L.P.-B.). Funding for open access charge: Ministerio de Ciencia e Innovación-Agencia Estatal de Investigación [BFU2016-77728-C3-1-P]

Human prefoldin modulates co-transcriptional pre-mRNA splicing

Trabajo presentado en el IV Meeting RNALife, celebrado en Sevilla (España) del 12 al 13 de julio de 2021.Prefoldin is a heterohexameric complex conserved from archaea to humans that plays a co-chaperone role during the co-translational folding of actin and tubulin monomers. Additional functions of prefoldin have been described, including a positive contribution to transcription elongation and chromatin dynamics in yeast. Here we show that prefoldin perturbations provoked transcriptional alterations across the human genome. Severe pre-mRNA splicing defects were also detected, particularly after serum stimulation. We found impairment of co-transcriptional splicing during transcription elongation, which explains why the induction of long genes with a high number of introns was affected the most. We detected genome-wide prefoldin binding to transcribed genes and found that it correlated with the negative impact of prefoldin depletion on gene expression. Lack of prefoldin caused global decrease in Ser2 and Ser5 phosphorylation of the RNA polymerase II carboxy-terminal domain. It also reduced the recruitment of the CTD kinase CDK9 to transcribed genes, and the association of splicing factors PRP19 and U2AF65 to chromatin, which is known to depend on CTD phosphorylation. Altogether the reported results indicate that human prefoldin is able to act locally on the genome to modulate gene expression by influencing phosphorylation of elongating RNA polymerase II, and thereby regulating co-transcriptional splicing

Evaluation of the COVID-19 response in Spain: principles and requirements

A resurgence of COVID-19 infections is occurring in Spain, with some of the worst figures in Europe. In August, 2020, we urged the Spanish Central Government and regional governments to independently evaluate their COVID-19 response to identify areas where public health and the health and social care system need to be improved

Insight on how to assess and improve the response to the COVID-19 pandemic

La pandemia de COVID-19 ha afectado de manera particularmente intensa a España, pese a su nivel de desarrollo y la elogiada solidez de su Sistema Nacional de Salud. Para comprender qué ha pasado e identificar cómo mejorar la respuesta creemos imprescindible una evaluación independiente multidisciplinaria de la esfera sanitaria, política y socioeconómica. En este trabajo proponemos objetivos, principios, metodología y dimensiones a evaluar, además de esbozar el tipo de resultados y conclusiones esperadas. Nos inspiramos en los requerimientos formulados por el panel independiente de la Organización Mundial de la Salud y en las experiencias evaluativas en otros países, y detallamos la propuesta de aspectos multidimensionales que deben valorarse. La idea es comprender aspectos clave en los ámbitos estudiados y su margen de mejora en lo relativo a preparación, gobernanza, marco normativo, estructuras del Sistema Nacional de Salud (atención primaria, hospitalaria y de salud pública), sector de educación, esquemas de protección social, minimización del impacto económico, y marco y reformas en el ámbito laboral para una sociedad más resiliente. En definitiva, buscamos que este ejercicio sirva no solo para el presente, sino también para que en el futuro estemos mejor preparados y con más ágil capacidad de recuperación ante las amenazas pandémicas que puedan surgir.The COVID-19 pandemic has hit Spain particularly hard, despite being a country with a developed economy and being praised for the robustness of its national health system. In order to understand what happened and to identify how to improve the response, we believe that an independent multi-disciplinary evaluation of the health, political and socio-economic spheres is essential. In this piece we propose objectives, principles, methodology and dimensions to be evaluated, as well as outlining the type of results and conclusions expected. Inspired by the requirements formulated by the WHO Independent Panel for Pandemic Preparedness and Response and by experiences in other countries, we detail the multidimensional aspects to be evaluated. The goal is to understand key aspects in the studied areas and their scope for improvement in terms of preparedness, governance, regulatory framework, national health system structures (primary care, hospital, and public health), education sector, social protection schemes, minimization of economic impact, and labour framework and reforms for a more resilient society. We seek to ensure that this exercise serves not only at present, but also that in the future we are better prepared and more agile in terms of our ability to recover from any pandemic threats that may arise.Ayuda referencia: PI 18/01937 del Fondo de Investigación Sanitaria- Instituto de Salud Carlos III, España, con cofinanciación de Fondos FEDER

Association of Candidate Gene Polymorphisms With Chronic Kidney Disease: Results of a Case-Control Analysis in the Nefrona Cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2, 445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD

Regulación fisiológica del promotor 'Pu' del plásmido TOL pWW0 de 'Pseudomonas putida'

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 20-11-199

Biochemical features associated to cancer mutations

Trabajo presentado en las XI Jornadas de Bioinformática, celebradas en Barcelona del 23 al 25 de enero de 2012.N