Degradation of the mycotoxin fusaric acid in burkholderia ambifaria t16: genes and metabolic pathways involved

Fusaric acid (FA, 5-butylpyridine, 2-carboxylic acid) is a secondary metabolite produced by several Fusarium species, which is toxic for bacteria, plants, animals and humans. This mycotoxin contributes to the virulence of phytopathogenic Fusarium in several crops, causing important economic losses. Moreover, FA reduces survival and competition abilities of bacterial species able to antagonize Fusarium spp. due to its negative effects on viability and production of antibiotics effective against these fungi. Burkholderia ambifaria T16 is a bacterial strain isolated from the rhizosphere of barley that showed the interesting ability to degrade FA and detoxify this mycotoxin from barley seedlings. The genes and metabolic pathways involved in FA degradation have not been identified so far in any bacterial species. By screening of a transposon insertion library and proteomic analysis we were able to identify genes and metabolic pathways that would be involved in FA degradation. A functional 2-methylcitrate cycle (2-MCC), a carbon anaplerotic pathway widely distributed among bacteria and fungi where propionyl-CoA is converted to pyruvate and succinate, was shown to be essential for the growth of B. ambifaria T16 in the presence of FA. Propionyl-CoA and its derived catabolites are lethally toxic to cells when accumulate. For that reason, besides providing succinate and pyruvate, the 2-MCC also has a very important role in the detoxification of propionyl-CoA and its catabolites. The comparison of the proteomic profile of B. ambifaria T16 growing with FA or citrate as sole carbon sources showed that more than 50 enzymes were significantly overexpressed during growth with FA, including 2-MCC enzymes and enzymes that convert butyryl-CoA to propanoyl-CoA, suggesting that propanoyl-CoA is produced during FA degradation. Moreover, several proteins, including an AraC-type transcriptional regulator, a FMN-dependent two-component luciferase like monooxygenase (LLM) system, an amidohydrolase, two enoyl-CoA hydratases and a long-chain fatty acid ligase, encoded in the same gene cluster, were highly over-expressed during growth with FA (>10 fold up-regulation). In the last years, two-component LLMs were shown to catalyze the pyridine-ring cleavage of several N-heterocyclic compounds, suggesting that the mentioned gene cluster is a good candidate to be involved in the initial steps of FA degradation in B. ambifaria T16.Fil: Vinacour, Matias Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales; ArgentinaFil: Forne, I.. Ludwig Maximilians Universitat; AlemaniaFil: Jung, K.. Ludwig Maximilians Universitat; AlemaniaFil: Imhof, A.. Ludwig Maximilians Universitat; AlemaniaFil: Ruiz, Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales. Universidad de Buenos Aires. Facultad de Agronomía. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales; ArgentinaLVII SAIB Meeting; XVI SAMIGE MeetingCiudad Autonoma de Buenos AiresArgentinaSociedad Argentina de Investigación Bioquímica y Biología MolecularSociedad Argentina de Microbiología Genera

Implementación de estrategias para la prevención y gestión integral de residuos sólidos urbanos en la comunidad de San Isidro Mazatepec, Tala

El documento recupera el proceso vivido para lograr contribuir a la concientización de la comunidad de San Isidro Mazatepec en cuanto a la prevención y el manejo de residuos. Las actividades realizadas fueron; talleres de concientización en primaria y preparatoria, planos para mejorar el funcionamiento del tratamiento de residuos orgánicos, exposiciones de documentales, implementación de herramienta para llevar control de entradas y salidas de dinero dentro del Centro de Acopio, y un manual para educar a la comunidad en San Isidro Mazatepec en tema de residuos.ITESO, A.C

Implementación de estrategias para la prevención y gestión integral de residuos sólidos urbanos en la comunidad de San Isidro Mazatepec, Tala

En el presente documento, se narra el trabajo realizado en el periodo de primavera 2019 por un equipo de profesionales pertenecientes al Instituto Tecnológico y de Estudios Superiores de Occidente (ITESO). El documento recupera el proceso vivido para lograr contribuir a la concientización de la comunidad de San Isidro Mazatepec en cuanto a la prevención y el manejo de residuos. Las actividades realizadas fueron; talleres de concientización en primaria y preparatoria, planos para mejorar el funcionamiento del tratamiento de residuos orgánicos, exposiciones de documentales, implementación de herramienta para llevar control de entradas y salidas de dinero dentro del Centro de Acopio, y un manual para educar a la comunidad en San Isidro Mazatepec en tema de residuos.ITESO, A.C

Available and missing data to model impact of climate change on European forests

Climate change is expected to cause major changes in forest ecosystems during the 21st century and beyond. To assess forest impacts from climate change, the existing empirical information must be structured, harmonised and assimilated into a form suitable to develop and test state-of-the-art forest and ecosystem models. The combination of empirical data collected at large spatial and long temporal scales with suitable modelling approaches is key to understand forest dynamics under climate change. To facilitate data and model integration, we identified major climate change impacts observed on European forest functioning and summarised the data available for monitoring and predicting such impacts. Our analysis of c. 120 forest-related databases (including information from remote sensing, vegetation inventories, dendroecology, palaeoecology, eddy-flux sites, common garden experiments and genetic techniques) and 50 databases of environmental drivers highlights a substantial degree of data availability and accessibility. However, some critical variables relevant to predicting European forest responses to climate change are only available at relatively short time frames (up to 10-20 years), including intra-specific trait variability, defoliation patterns, tree mortality and recruitment. Moreover, we identified data gaps or lack of data integration particularly in variables related to local adaptation and phenotypic plasticity, dispersal capabilities and physiological responses. Overall, we conclude that forest data availability across Europe is improving, but further efforts are needed to integrate, harmonise and interpret this data (i.e. making data useable for non-experts). Continuation of existing monitoring and networks schemes together with the establishments of new networks to address data gaps is crucial to rigorously predict climate change impacts on European forests. © 2019 The Author(s

Available and missing data to model impact of climate change on European forests

Climate change is expected to cause major changes in forest ecosystems during the 21st century and beyond. To assess forest impacts from climate change, the existing empirical information must be structured, harmonised and assimilated into a form suitable to develop and test state-of-the-art forest and ecosystem models. The combination of empirical data collected at large spatial and long temporal scales with suitable modelling approaches is key to understand forest dynamics under climate change. To facilitate data and model integration, we identified major climate change impacts observed on European forest functioning and summarised the data available for monitoring and predicting such impacts. Our analysis of c. 120 forest-related databases (including information from remote sensing, vegetation inventories, dendroecology, palaeoecology, eddy-flux sites, common garden experiments and genetic techniques) and 50 databases of environmental drivers highlights a substantial degree of data availability and accessibility. However, some critical variables relevant to predicting European forest responses to climate change are only available at relatively short time frames (up to 10-20 years), including intra-specific trait variability, defoliation patterns, tree mortality and recruitment. Moreover, we identified data gaps or lack of data integration particularly in variables related to local adaptation and phenotypic plasticity, dispersal capabilities and physiological responses. Overall, we conclude that forest data availability across Europe is improving, but further efforts are needed to integrate, harmonise and interpret this data (i.e. making data useable for non-experts). Continuation of existing monitoring and networks schemes together with the establishments of new networks to address data gaps is crucial to rigorously predict climate change impacts on European forests.Peer reviewe

Follicular fluid content and oocyte quality: from single biochemical markers to metabolomics

The assessment of oocyte quality in human in vitro fertilization (IVF) is getting increasing attention from embryologists. Oocyte selection and the identification of the best oocytes, in fact, would help to limit embryo overproduction and to improve the results of oocyte cryostorage programs. Follicular fluid (FF) is easily available during oocyte pick-up and theorically represents an optimal source on non-invasive biochemical predictors of oocyte quality. Unfortunately, however, the studies aiming to find a good molecular predictor of oocyte quality in FF were not able to identify substances that could be used as reliable markers of oocyte competence to fertilization, embryo development and pregnancy. In the last years, a well definite trend toward passing from the research of single molecular markers to more complex techniques that study all metabolites of FF has been observed. The metabolomic approach is a powerful tool to study biochemical predictors of oocyte quality in FF, but its application in this area is still at the beginning. This review provides an overview of the current knowledge about the biochemical predictors of oocyte quality in FF, describing both the results coming from studies on single biochemical markers and those deriving from the most recent studies of metabolomic

The T309G MDM2 gene polymorphism is a novel risk factor for proliferative vitreoretinopathy

Proliferative vitreoretinopathy (PVR) is still the major cause of failure in retinal detachment (RD) surgery. It is believed that down-regulation in the p53 pathway could be an important key in PVR pathogenesis. The purpose was to evaluate the impact of T309G MDM2 polymorphism (rs2279744) in PVR. Distribution of T309G MDM2 genotypes among European subjects undergoing RD surgery was evaluated. Proportions of genotypes between subsamples from different countries were analyzed. Also, a genetic interaction between rs2279744 in MDM2 and rs1042522 in p53 gene was analyzed. Significant differences were observed comparing MDM2 genotype frequencies at position 309 of intron 1 between cases (GG: 21.6%, TG: 54.5%, TT: 23.8%) and controls (GG: 7.3%, TG: 43.9%, TT: 48.7%). The proportions of genotypes between sub-samples from different countries showed a significant difference. Distribution of GG genotype revealed differences in Spain (35.1-53.0)/(22.6-32.9), Portugal (39.0-74.4)/(21.4-38.9), Netherlands (40.6-66.3)/(25.3-38.8) and UK (37.5-62.4)/(23.3-34.2). The OR of G carriers in the global sample was 5.9 (95% CI: 3.2 to 11.2). The OR of G carriers from Spain and Portugal was 5.4 (95% CI: 2.2-12.7), whereas in the UK and the Netherlands was 7.3 (95% CI: 2.8-19.1). Results indicate that the G allele of rs2279744 is associated with a higher risk of developing PVR in patients undergoing a RD surgery. Further studies are necessary to understand the role of this SNP in the development of PVR. Copyright

CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice.

Neuroinflammation and microglial activation are significant processes in Alzheimer's disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer's disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer's disease and other tau-mediated neurodegenerative diseases.Funded by a grant from the Wellcome Trust (Grant number: 104025/Z/14/Z), and by the NIHR Oxford Health Biomedical Research Centre

CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice

Neuroinflammation and microglial activation are significant processes in Alzheimer’s disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer’s disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer’s disease and other tau-mediated neurodegenerative diseases