51 research outputs found

    Cambios en los patrones de endemismo de los mamíferos terrestres de México por el calentamiento global

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    ResumenExisten algunos análisis acerca del impacto del cambio climático en la distribución de los mamíferos terrestres de México. Sin embargo, los impactos en las áreas de endemismo no han sido analizados. Por esto, el objetivo de este análisis fue determinar los efectos del cambio climático en los patrones de endemismo de los mamíferos de México, dado las diferencias climáticas entre 2 períodos, el presente (1961-1990) y el futuro (2080-2099). Para ello, se obtuvieron 405 modelos de distribución de especies de los mamíferos terrestres de México, aplicando un algoritmo de máxima entropía (MaxEnt), y haciendo una proyección futura bajo el escenario climático A2 de acuerdo a 3 modelos de circulación general. Posteriormente, se realizó un análisis de endemicidad para identificar las áreas de endemismo y sus taxones endémicos. Se identificaron 23 áreas de endemismo en el presente, mientras que en las proyecciones futuras se obtuvieron de 14 a 16. Por último, se presenta una comparación entre los 2 periodos usando un análisis espacial y midiendo la vulnerabilidad de las áreas de endemismo con un factor relativo de vulnerabilidad. La pérdida de patrones de endemismo, el desplazamiento geográfico, la reducción de superficies y el cambio en la composición de especies de las áreas de endemismo, muestran el impacto negativo que puede provocar el calentamiento global en los patrones de endemismo.AbstractThere are some analyses about the impact of climatic change in the distribution of Mexican land mammals. However, this impact has not been analyzed on areas of endemism. For this reason, the aim of this analysis was to determine the climate change effects in the patterns of endemism of the mammals of Mexico, regarding the climatic differences between 2 time periods, present time (1961-1990) and future time (2080-2099). For this purpose, 405 species distribution models of the Mexican land mammals were obtained applying a maximum entropy algorithm (MaxEnt), and using their projections under climate scenario A2 according to 3 general circulation models. Later, an Endemicity Analysis was performed in order to identify areas of endemism and their endemic taxa. Twenty-three areas of endemism in the present time were identified, while 14-16 areas of endemism were identified for the future time. Finally, a comparison between present and future time is presented, using spatial analysis and measuring vulnerability of the areas of endemicity with a relative vulnerability factor. Loss of patterns of endemism, geographic displacement, surfaces reduction and change in species composition of the areas of endemism show the negative impact that global warming may cause on the endemism patterns

    Multifunctional albumin-stabilized gold nanoclusters for the reduction of cancer stem cells

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    Controlled delivery of multiple chemotherapeutics can improve the effectiveness of treatments and reduce side effects and relapses. Here in, we used albumin-stabilized gold nanoclusters modified with doxorubicin and SN38 (AuNCs-DS) as combined therapy for cancer. The chemotherapeutics are conjugated to the nanostructures using linkers that release them when exposed to different internal stimuli (Glutathione and pH). This system has shown potent antitumor activity against breast and pancreatic cancer cells. Our studies indicate that the antineoplastic activity observed may be related to the reinforced DNA damage generated by the combination of the drugs. Moreover, this system presented antineoplastic activity against mammospheres, a culturing model for cancer stem cells, leading to an efficient reduction of the number of oncospheres and their size. In summary, the nanostructures reported here are promising carriers for combination therapy against cancer and particularly to cancer stem cells.This research was funded by the Spanish Ministry of Economy and Competitiveness (CTQ2016-78454-C2-2-R, SAF2014-56763-R, and SAF2017-87305-R), Comunidad de Madrid (S2013/MIT-2850), Asociación Española Contra el Cáncer, and IMDEA Nanociencia IMDEA Nanociencia acknowledges support from the ‘Severo Ochoa’ Programme for Centres of Excellence in R&D (MINECO, Grant SEV-2016-0686

    Cannabinoid CB1 receptor gene inactivation in oligodendrocyte precursors disrupts oligodendrogenesis and myelination in mice

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    [EN] Cannabinoids are known to modulate oligodendrogenesis and developmental CNS myelination. However, the cell-autonomous action of these compounds on oligodendroglial cells in vivo, and the molecular mechanisms underlying these effects have not yet been studied. Here, by using oligodendroglial precursor cell (OPC)-targeted genetic mouse models, we show that cannabinoid CB1 receptors exert an essential role in modulating OPC differentiation at the critical periods of postnatal myelination. We found that selective genetic inactivation of CB1 receptors in OPCs in vivo perturbs oligodendrogenesis and postnatal myelination by altering the RhoA/ROCK signaling pathway, leading to hypomyelination, and motor and cognitive alterations in young adult mice. Conversely, pharmacological CB1 receptor activation, by inducing E3 ubiquitin ligase-dependent RhoA proteasomal degradation, promotes oligodendrocyte development and CNS myelination in OPCs, an effect that was not evident in OPC-specific CB1 receptor-deficient mice. Moreover, pharmacological inactivation of ROCK in vivo overcomes the defects in oligodendrogenesis and CNS myelination, and behavioral alterations found in OPC-specific CB1 receptor-deficient mice. Overall, this study supports a cell-autonomous role for CB1 receptors in modulating oligodendrogenesis in vivo, which may have a profound impact on the scientific knowledge and therapeutic manipulation of CNS myelination by cannabinoids.This work was supported by the MINECO grants SAF2017-83516 and PID2020-112640RB-I00, and the Comunidad de Madrid grants 2016-T1/BMD-1060 and 2020-5 A/BMD-19728, Atraccion del Talento Investigador Program, to JP. AHG and TA. AHG was also supported by the Comunidad de Madrid contract PEJD-2017PRE/BMD-3703, and A.S.T by Fundacion Tatiana Perez de Guzman el Bueno. Support was also provided by MINECO (grants RTI2018-095311-B-I00 to MG. and SAF2016-75292-R to CM), CIBERNED (grants CB06/05/0005 to M.G. and CB06/0005/0076 to C.M.), FEDER and ISCIII (AES 2018 grants PI18-00941 to IG-R and PI18/00513 to SM), Basque Government (grants IT1203-19 to C.M. and PIBA19-0059 to SM), and ARSEP Foundation (grant to SM)

    Δ 9 ‐Tetrahydrocannabinol promotes functional remyelination in the mouse brain

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    Background and purpose: Research on demyelinating disorders aims to find novel molecules that are able to induce oligodendrocyte precursor cell differentiation to promote central nervous system remyelination and functional recovery. Δ9 -Tetrahydrocannabinol (THC), the most prominent active constituent of the hemp plant Cannabis sativa, confers neuroprotection in animal models of demyelination. However, the possible effect of THC on myelin repair has never been studied. Experimental approach: By using oligodendroglia-specific reporter mouse lines in combination with two models of toxin-induced demyelination, we analysed the effect of THC on the processes of oligodendrocyte regeneration and functional remyelination. Key results: We show that THC administration enhanced oligodendrocyte regeneration, white matter remyelination and motor function recovery. THC also promoted axonal remyelination in organotypic cerebellar cultures. THC remyelinating action relied on the induction of oligodendrocyte precursor differentiation upon cell cycle exit and via CB1 cannabinoid receptor activation. Conclusions and implications: Overall, our study identifies THC administration as a promising pharmacological strategy aimed to promote functional CNS remyelination in demyelinating disorders

    Effect of mistimed eating patterns on breast and prostate cancer risk (MCC-Spain Study)

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    Modern life involves mistimed sleeping and eating patterns that in experimental studies are associated with adverse health effects. We assessed whether timing of meals is associated with breast and prostate cancer risk taking into account lifestyle and chronotype, a characteristic correlating with preference for morning or evening activity. We conducted a population-based case-control study in Spain, 2008-2013. In this analysis we included 621 cases of prostate and 1,205 of breast cancer and 872 male and 1,321 female population controls who had never worked night shift. Subjects were interviewed on timing of meals, sleep and chronotype and completed a Food Frequency Questionaire. Adherence to the World Cancer Research Fund/American Institute of Cancer Research recommendations for cancer prevention was examined. Compared with subjects sleeping immediately after supper, those sleeping two or more hours after supper had a 20% reduction in cancer risk for breast and prostate cancer combined (adjusted Odds Ratio [OR] = 0.80, 95%CI 0.67-0.96) and in each cancer individually (prostate cancer OR = 0.74, 0.55-0.99; breast cancer OR = 0.84, 0.67-1.06). A similar protection was observed in subjects having supper before 9 pm compared with supper after 10 pm. The effect of longer supper-sleep interval was more pronounced among subjects adhering to cancer prevention recommendations (OR both cancers= 0.65, 0.44-0.97) and in morning types (OR both cancers = 0.66, 0.49-0.90). Adherence to diurnal eating patterns and specifically a long interval between last meal and sleep are associated with a lower cancer risk, stressing the importance of evaluating timing in studies on diet and cancer

    Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

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    The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

    Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

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    Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries
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