Genome scale metabolic modeling reveals the metabolic potential of three Type II methanotrophs of the genus Methylocystis

Producción CientíficaGenome Scale Metabolic Models (GSMMs) of the recently sequenced Methylocystis hirsuta and two other methanotrophs from the genus Methylocystis have been reconstructed. These organisms are Type II methanotrophs with the ability of accumulating Polyhydroxyalkanoates under nutrient limiting conditions. For the first time, GSMMs have been reconstructed for Type II methanotrophs. These models, combined with experimental biomass and PHB yields of Methylocystis hirsuta, allowed elucidating the methane oxidation mechanism by the enzyme pMMO (particulate methane monooxygenase) in these organisms. In contrast to Type I methanotrophs, which use the “direct coupling mechanism”, Type II methanotrophs appear to use the so called “redox arm mechanism”. The utilization of the “redox arm mechanism”, which involves the coupling between methane oxidation and complex I of the respiratory chain, was confirmed by inhibition of complex I with catechol. Utilization of the “redox arm” mechanism leads to lower biomass yields on methane compared to Type I methanotrophs. However, the ability of Type II methanotrophs to redirect high metabolic carbon fluxes towards acetoacetyl-CoA under nitrogen limiting conditions makes these organisms promising platforms for metabolic engineering.Marie Curie grant H2020-MSCA-IF-2016 CH4BioVal (GA nº 750126).Junta de Castilla y León (Ref. Project VA281P18)Ministerio de Ciencia e Innovación (Proyect CLU 2017-09, CTM2015-70442-R

Genome sequence of Methylocystis hirsuta CSC1, a polyhydroxyalkanoate producing methanotroph

Producción CientíficaPolyhydroxyalkanoates (PHAs) are biodegradable plastics that can be produced by some methanotrophic organisms such as those of the genus Methylocystis. This allows the conversion of a detrimental greenhouse gas into an environmentally friendly high added‐value bioproduct. This study presents the genome sequence of Methylocystis hirsuta CSC1 (a high yield PHB producer). The genome comprises 4,213,043 bp in 4 contigs, with the largest contig being 3,776,027 bp long. Two of the other contigs are likely to correspond to large size plasmids. A total of 4,664 coding sequences were annotated, revealing a PHA production cluster, two distinct particulate methane monooxygenases with active catalytic sites, as well as a nitrogen fixation operon and a partial denitrification pathway.Ministerio de Ciencia e Innovación (Proyect CTM2015‐70442‐R)Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. Project UIC 71

The effect of temperature during culture enrichment on methanotrophic polyhydroxyalkanoate production

Producción CientíficaClimate change and plastic pollution are likely the most relevant environmental problems of the 21st Century. Thus, one of the most promising solutions to remedy both environmental problems simultaneously is the bioconversion of greenhouse gases, such as methane (CH4), into bioplastics (PHAs). However, the optimization of this bioconversion platform is still required to turn CH4 biotransformation into a cost-effective and cost-competitive process. In this context, the research presented here aimed at elucidating the best temperature culture conditions to enhance both PHA accumulation and methane degradation. Six different enrichments were carried out at 25, 30 and 37 °C using different inocula and methane as the only energy and carbon source. CH4 biodegradation rates, specific growth rates, PHA accumulations and the community structure were characterized. Higher temperatures (30 and 37 °C) increased the PHAs accumulation up to 30% regardless of the inoculum. Moreover, Methylocystis became the dominant genus (∼30% of the total population) regardless of the temperature and inoculum used. This research demonstrated for the first time the fundamental role of temperature in increasing both the accumulation of PHAs and methane abatement during the enrichment of PHA cell-factories from methane, thus enhancing the cost-effectiveness of the process.Ministerio de Economía, Industria y Competitividad, TheEuropean FEDER program and the European Commission (CTM2015-73228-JIN, H2020-MSCA-IF-2016: CH4BioVal-GA:750126 and Red NOVEDAR)

ERK5 Is a Major Determinant of Chemical Sarcomagenesis: Implications in Human Pathology.

Abstract: Sarcomas are a heterogeneous group of tumors in which the role of ERK5 is poorly studied. To clarify the role of this MAPK in sarcomatous pathology, we used a murine 3-methyl-cholanthrene (3MC)-induced sarcoma model. Our data show that 3MC induces pleomorphic sarcomas with muscle differentiation, showing an increased expression of ERK5. Indeed, this upregulation was also observed in human sarcomas of muscular origin, such as leiomyosarcoma or rhabdomyosarcoma. Moreover, in cell lines derived from these 3MC-induced tumors, abrogation of Mapk7 expression by using specific shRNAs decreased in vitro growth and colony-forming capacity and led to a marked loss of tumor growth in vivo. In fact, transcriptomic profiling in ERK5 abrogated cell lines by RNAseq showed a deregulated gene expression pattern for key biological processes such as angiogenesis, migration, motility, etc., correlating with a better prognostic in human pathology. Finally, among the various differentially expressed genes, Klf2 is a key mediator of the biological effects of ERK5 as indicated by its specific interference, demonstrating that the ERK5–KLF2 axis is an important determinant of sarcoma biology that should be further studied in human pathology.pre-print9446 K

Molecular Alterations in Pancreatic Cancer: Transfer to the Clinic.

Pancreatic ductal adenocarcinoma (PDA) is the most common cancer of the exocrine pancreas and probably the tumor that has benefited the least from clinical progress in the last three decades. A consensus has been reached regarding the histologic classification of the ductal preneoplastic lesions (pancreatic intra-epithelial neoplasia—PanIN) and the molecular alterations associated with them. Mutations in KRAS and inactivation of CDKN2A, SMAD4 and TP53 are among the most prevalent alterations. Next generation sequencing studies are providing a broad picture of the enormous heterogeneity in this tumor type, describing new mutations less prevalent. These studies have also allowed the characterization of different subtypes with prognostic value. However, all this knowledge has not been translated into a clinical progress. Effective preventive and early diagnostic strategies are essential to improve the survival rates. The main challenge is, indeed, to identify new effective drugs. Despite many years of research and its limited success, gemcitabine is still the first line treatment of PDA. New drug combinations and new concepts to improve drug delivery into the tumor, as well as the development of preclinical predictive assays, are being explored and provide optimism and prospects for better therapies.post-print335 K

Recent trends and advances in biogas upgrading and methanotrophs-based valorization

Producción CientíficaThe global quest for sustainability in industrial activities and waste management has recently boosted biogas production worldwide. However, the rapid decrease in the levelized cost of electricity of renewable energies will soon entail electricity prices from biogas much higher than those from solar or wind power. In this context, the upgrading of biogas into biomethane represents an alternative to on-site biogas combustion. Membrane separation technology is rapidly dominating the biogas upgrading market and displacing scrubbing and adsorption technologies driven by the recent breakthroughs in material science. Similarly, biogas biorefineries have recently emerged as an innovative platform for biogas valorization capable of biotransforming methane into added value products. The limited number of bioproducts naturally synthesized by methanotrophs can be boosted via metabolic engineering of methanotrophs, while novel bioreactor configurations capable of supporting a cost-effective methane mass transfer from the gas phase to the methanotrophic broth are currently under investigation to facilitate the full scale implementation of biogas biorefineries.Junta de Castilla y Leon - FEDER (program CLU 2017–09, CL-EI-2021–07 and UIC 315)European Commission-H2020-MSCA-IF-2019 project UP-GRAD (894515)Ministerio de Ciencia, Innovación y Universidades (project IJC2019–040495-I

Biodegradation of bioplastics under aerobic and anaerobic aqueous conditions: Kinetics, carbon fate and particle size effect

Producción CientíficaThe biodegradation of PHB, PHBV, PBS, PBAT, PCL, PLA, and a PLA-PCL blend was systematically compared under aerobic and anaerobic aqueous conditions assessing biodegradation kinetics, extent, carbon fate and particle size influence (in the range of 100–1000 µm). Under standard test conditions, PHB and PBHV were biodegraded anaerobically (83.9±1.3% and 81.2±1.7%, respectively) in 77 days or aerobically (83.0±1.6% and 87.4±7.5%) in 117 days, while PCL was only biodegraded (77.6±2.4%) aerobically in 177 days. Apparent biomass growth accounted for up to 30.5% of the total initial carbon depending on the bioplastic and environment. Maximum aerobic and anaerobic biodegradation rates were improved up to 331 and 405%, respectively, at the lowest particle size tested (100–250 µm). This study highlights the usefulness of a more detailed analysis of biodegradation kinetics and carbon fate to improve both the development and testing of biodegradable materials/products in the context of a circular bioeconomy.Junta de Castilla y León - Fondo Europeo de Desarrollo Regional (projects CLU 2017-09 and UIC 315

ERK5 Is a major determinant of chemical sarcomagenesis: implications in human pathology

Sarcomas are a heterogeneous group of tumors in which the role of ERK5 is poorly studied. To clarify the role of this MAPK in sarcomatous pathology, we used a murine 3-methyl-cholanthrene (3MC)-induced sarcoma model. Our data show that 3MC induces pleomorphic sarcomas with muscle differentiation, showing an increased expression of ERK5. Indeed, this upregulation was also observed in human sarcomas of muscular origin, such as leiomyosarcoma or rhabdomyosarcoma. Moreover, in cell lines derived from these 3MC-induced tumors, abrogation of Mapk7 expression by using specific shRNAs decreased in vitro growth and colony-forming capacity and led to a marked loss of tumor growth in vivo. In fact, transcriptomic profiling in ERK5 abrogated cell lines by RNAseq showed a deregulated gene expression pattern for key biological processes such as angiogenesis, migration, motility, etc., correlating with a better prognostic in human pathology. Finally, among the various differentially expressed genes, Klf2 is a key mediator of the biological effects of ERK5 as indicated by its specific interference, demonstrating that the ERK5–KLF2 axis is an important determinant of sarcoma biology that should be further studied in human pathology.This work has been supported with Grant RTI2018-094093-B-I00 funded by MCIN/AEI/10.13039/501100011033, “ERDF A way of making Europe” to RSP. Also supported with funds from Fundación Leticia Castillejo Castillo, Roche España and ACEPAIN to RSP and MJRH. RSP and MJRH’s Research Institute and the work carried out in their laboratory, received partial support from the European Community through the FEDER. JJ and EAL hold a predoctoral research contract cofounded by the European Social Fund and UCLM. OR holds a contract for accessing the Spanish System of Science, Technology, and Innovation (SECTI) funded by the University of Castilla-La Mancha (UCLM) and received partial support from the European Social Fund (FSE) through its Operative Program for Castilla-La Mancha (2007–2013)

ERK5 Is a Major Determinant of Chemical Sarcomagenesis : Implications in Human Pathology

Sarcoma is a heterogeneous group of tumors poorly studied with few therapeutic opportunities. Interestingly, the role of MAPKs still remains unclear in sarcomatous pathology. Here, we describe for the first time the critical role of ERK5 in the biology of soft tissue sarcoma by using in vitro and in vivo approaches in a murine experimental model of chemical sarcomagenesis. Indeed, our observations were extrapolated to a short series of human leiomyosarcoma and rhabdomyosarcomas. Furthermore, transcriptome analysis allows us to demonstrate the critical role of KLF2 in the biological effects of ERK5. Therefore, the data presented here open new windows in the diagnosis and therapy of soft tissue sarcomas. Sarcomas are a heterogeneous group of tumors in which the role of ERK5 is poorly studied. To clarify the role of this MAPK in sarcomatous pathology, we used a murine 3-methyl-cholanthrene (3MC)-induced sarcoma model. Our data show that 3MC induces pleomorphic sarcomas with muscle differentiation, showing an increased expression of ERK5. Indeed, this upregulation was also observed in human sarcomas of muscular origin, such as leiomyosarcoma or rhabdomyosarcoma. Moreover, in cell lines derived from these 3MC-induced tumors, abrogation of Mapk7 expression by using specific shRNAs decreased in vitro growth and colony-forming capacity and led to a marked loss of tumor growth in vivo. In fact, transcriptomic profiling in ERK5 abrogated cell lines by RNAseq showed a deregulated gene expression pattern for key biological processes such as angiogenesis, migration, motility, etc., correlating with a better prognostic in human pathology. Finally, among the various differentially expressed genes, Klf2 is a key mediator of the biological effects of ERK5 as indicated by its specific interference, demonstrating that the ERK5-KLF2 axis is an important determinant of sarcoma biology that should be further studied in human pathology

Multiliteracidad crítica: Guía de recursos online para la formación inicial y permanente del profesorado

El proyecto de innovación docente nº 412, titulado Multiliteracidad crítica: Guía de recursos online para la formación inicial y permanente del profesorado, desarrollado en la Facultad de Educación de la UCM durante el curso 2020-21, es continuación de tres proyectos de innovación anteriores identificados como Géneros y sociedad I, II y III. Los tres proyectos tienen su origen en el proyecto multilateral Comenius Teacher Learning for European Literacy Education (TeL4ELE), que nació con el objetivo de mejorar los resultados de aprendizaje de lectura y escritura de estudiantes de educación obligatoria. En el curso 2020-21, el grupo de investigación implicado en estos proyectos (ForMuLE) orienta sus propuestas de innovación docente en los grados de Maestro hacia la alfabetización multimodal. Entre los objetivos generales del proyecto se planteó la creación de una guía de recursos guía de recursos multimedia que ofrezca herramientas para analizar de manera adecuada textos y recursos multimodales desde una perspectiva crítica, tanto a estudiantes del Grado y postgrado de formación del profesorado, como a profesores en activo de diferentes niveles educativos