Plasma endocannabinoids as potential biomarkers of type 2 diabetes mellitus in elderly patients with mild cognitive impairment

Background: Besides their role in the nervous system and the development of cognitive impairment in elderly patients, compelling evidence suggests that endocannabinoids (ECBs) are related to motivational responses in obesity and the development of insulin resistance and diabetes. Few studies indicate that ECBs modulate insulin secretion via cannabinoid receptors (CBs) in the human pancreas and alter glucose metabolism. Objectives: The present cross-sectional study aims to evaluate the association between plasma ECBs and the incidence of type 2 diabetes mellitus (T2DM) in a cohort of elderly patients with mild cognitive impairment (MCI). We also aimed to identify possible associations between brain metabolism as determined by PET-18FDG in T2DM patients and plasma levels of ECBs and diabetes-related metabolites. The sample included age and gender-matched MCI patients without (non-T2DM, n = 113) and with T2DM diagnostic (n = 49). Results: T2DM patients presented higher levels of acyl glycerols 2-AG and 2-OG, whereas DHEA was significantly decreased as compared to non-T2DM patients. Moreover, 2-AG and 2-OG were significantly associated with the triglyceride/glucose (TyG) index, a surrogate marker of insulin-resistance. 2-AG and 2-OG plasma levels were significantly associated with cognitive decline determined by MMSE and BLESSED tests, specifically in non-T2DM patients, but not in T2DM patients. T2DM patients showed hypermetabolism specifically in the hippocampus, parahippocampus and amygdala, brain regions associated with control of memory, decision-making, and social cognition. We performed binary logistic regression with stepwise selection of variables including ECBs, GLP-1, C-Peptide, insulin, glucagon, leptin, glucose, triglycerides, and cholesterol molecules in order to create a predictive model of T2DM in elderly patients with MCI. We selected glucose (standardized β: 2.215), 2-OG (standardized β: 0.519), and LDL (standardized β: -0.649), with a positive predictive power of T2DM diagnosis of 89.74%, and an AUC of 0.87 in the ROC curve. We created a surrogate marker of T2DM in elderly patients consisting of variables selected (ECB-T2DM index: (Ln(4*glucose + 2-OG)/Ln(LDL)), which was significantly associated with glucose metabolism in hippocampus, parahippocampus and amygdala. Conclusions: Plasma 2-OG is a promising biomarker of T2DM in elderly patients with MCI and is associated with altered brain metabolism.Background: Besides their role in the nervous system and the development of cognitive impairment in elderly patients, compelling evidence suggests that endocannabinoids (ECBs) are related to motivational responses in obesity and the development of insulin resistance and diabetes. Few studies indicate that ECBs modulate insulin secretion via cannabinoid receptors (CBs) in the human pancreas and alter glucose metabolism. Objectives: The present cross-sectional study aims to evaluate the association between plasma ECBs and the incidence of type 2 diabetes mellitus (T2DM) in a cohort of elderly patients with mild cognitive impairment (MCI). We also aimed to identify possible associations between brain metabolism as determined by PET-18FDG in T2DM patients and plasma levels of ECBs and diabetes-related metabolites. The sample included age and gender-matched MCI patients without (non-T2DM, n = 113) and with T2DM diagnostic (n = 49). Results: T2DM patients presented higher levels of acyl glycerols 2-AG and 2-OG, whereas DHEA was significantly decreased as compared to non-T2DM patients. Moreover, 2-AG and 2-OG were significantly associated with the triglyceride/glucose (TyG) index, a surrogate marker of insulin-resistance. 2-AG and 2-OG plasma levels were significantly associated with cognitive decline determined by MMSE and BLESSED tests, specifically in non-T2DM patients, but not in T2DM patients. T2DM patients showed hypermetabolism specifically in the hippocampus, parahippocampus and amygdala, brain regions associated with control of memory, decision-making, and social cognition. We performed binary logistic regression with stepwise selection of variables including ECBs, GLP-1, C-Peptide, insulin, glucagon, leptin, glucose, triglycerides, and cholesterol molecules in order to create a predictive model of T2DM in elderly patients with MCI. We selected glucose (standardized β: 2.215), 2-OG (standardized β: 0.519), and LDL (standardized β: -0.649)...Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

GABAergic deficits in absence of LPA1 receptor, associated anxiety-like and coping behaviors, and amelioration by interneuron precursor transplants into the dorsal hippocampus

Defects in GABAergic function can cause anxiety- and depression-like behaviors among other neuropsychiatric disorders. Therapeutic strategies using the transplantation of GABAergic interneuron progenitors derived from the medial ganglionic eminence (MGE) into the adult hippocampus reversed the symptomatology in multiple rodent models of interneuron-related pathologies. In turn, the lysophosphatidic acid receptor LPA has been reported to be essential for hippocampal function. Converging evidence suggests that deficits in LPA receptor signaling represent a core feature underlying comparable hippocampal dysfunction and behaviors manifested in common neuropsychiatric conditions. Here, we first analyzed the GABAergic interneurons in the hippocampus of wild-type and maLPA-null mice, lacking the LPA receptor. Our data revealed a reduction in the number of neurons expressing GABA, calcium-binding proteins, and neuropeptides such as somatostatin and neuropeptide Y in the hippocampus of maLPA-null mice. Then, we used interneuron precursor transplants to test links between hippocampal GABAergic interneuron deficit, cell-based therapy, and LPA receptor-dependent psychiatric disease-like phenotypes. For this purpose, we transplanted MGE-derived interneuron precursors into the adult hippocampus of maLPA-null mice, to test their effects on GABAergic deficit and behavioral symptoms associated with the absence of the LPA receptor. Transplant studies in maLPA-null mice showed that grafted cells were able to restore the hippocampal host environment, decrease the anxiety-like behaviors and neutralize passive coping, with no abnormal effects on motor activity. Furthermore, grafted MGE-derived cells maintained their normal differentiation program. These findings reinforce the use of cell-based strategies for brain disorders and suggest that the LPA receptor represents a potential target for interneuron-related neuropsychiatric disorders.This work was supported by grants from the Spanish Ministry of Science, Innovation and Universities, co-funded by the European Regional Development Fund (ERDF, EU), (PSI2017-82604R, to LJS; PSI2017-83408-P to CP; SAF09-07746, to MAD; PI16/01510, to GET) and Andalusian Regional Ministries of Economy, Knowledge, Business and University (SEJ-4515 -to LJS; SEJ1863 to CP) and of Health and Families (Nicolas Monardes Programme to GET)

Organic Farming e-book

A agricultura biológica está-se a tornar cada vez mais importante como um caminho preferencial para a produção de produtos agrícolas, face à crescente procura do mercado mundial. A relevância da agricultura biológica é ainda maior, devido à necessidade e procura de produtos agrícolas de origem biológica, que são isentos de produtos químicos, saudáveis e amigos do ambiente. Atualmente, a agricultura biológica resulta em produtos de valor acrescentado, mas estes sistemas de produção exigem abordagens especializadas. Verifica-se uma lacuna de conhecimento especializado para enfrentar os desafios e exigências da agricultura biológica. Além disso, um número crescente de pessoas com níveis elevados de educação está a mudar a sua atividade para a agricultura sem qualquer tipo de formação nesta área técnica, principalmente em países com dificuldades económicas, como Portugal. Há, portanto, necessidade de desenvolver a capacidade de pessoas com algum tipo de qualificação prévio, a fim de melhorar suas competências agrícolas e facilitar a sua capacidade de desempenho e inovação, para que possam contribuir para a Estratégia Europeia (CE) de Desenvolvimento Rural. Este e-book foi concebido para melhorar as competências desses agricultores. O seu objectivo geral é dotar os novos agricultores com conhecimentos e capacidades necessários para o desenvolvimento da cadeia de valor dos produtos da agricultura biológica. Os objectivos específicos são: i) Fornecer conhecimento básico em vários aspectos da agricultura biológica e áreas afins, tais como a gestão de recursos naturais (solo, água, plantas, ambiente) e desenvolvimento rural (conservação, agricultura biológica e familiar, multifuncionalidade). ii) Facilitar a troca efetiva de conhecimento e experiências em agricultura biológica, desenvolvimento rural e ambiente. iii) Oferecer suporte técnico e conhecimento em agricultura biológica num contexto de mobilidade e em ambiente de trabalho. Este e-livro, produzido em sete idiomas diferentes (Português, Inglês, Espanhol, Italiano, Eslovaco, Turco e Húngaro) também contribui para preservar línguas e culturas Europeias e, assim, melhorar a comunicação entre os diferentes intervenientes e grupos-alvo. O e-book inclui os princípios e técnicas da agricultura biológica, com base no triângulo planta-solo-ambiente e nas relações entre a produção animal e o ambiente. A preparação de alimentos e rotulagem, marketing e conversão à agricultura biológica são também abordados. Os princípios e as técnicas apresentadas são explicados com base em regras e diretrizes (normas), baseados numa abordagem logística que garante o equilíbrio e integridade do sistema. O e-book apresenta também os regulamentos e normas nacionais e Europeias que são obrigatórias para os agricultores biológicos.info:eu-repo/semantics/publishedVersio

Impact of COVID-19 confinement on physical activity and sedentary behaviour in Spanish university students: role of gender

During the COVID-19 pandemic, entire populations were instructed to live in home-confinement to prevent the expansion of the disease. Spain was one of the countries with the strictest conditions, as outdoor physical activity was banned for nearly two months. This study aimed to analyse the changes in physical activity and sedentary behaviours in Spanish university students before and during the confinement by COVID-19 with special focus on gender. We also analysed enjoyment, the tools used and motivation and impediments for doing physical activity. An online questionnaire, which included the International Physical Activity Questionnaire Short Form and certain 'ad hoc' questions, was designed. Students were recruited by distributing an invitation through the administrative channels of 16 universities and a total of 13,754 valid surveys were collected. Overall, university students reduced moderate (-29.5%) and vigorous (-18.3%) physical activity during the confinement and increased sedentary time (+52.7%). However, they spent more time on high intensity interval training (HIIT) (+18.2%) and mind-body activities (e.g., yoga) (+80.0%). Adaptation to the confinement, in terms of physical activity, was handled better by women than by men. These results will help design strategies for each gender to promote physical activity and reduce sedentary behaviour during confinement periods.This research was funded by the High Sports Council (Consejo Superior de Deportes, CSD) of the Ministry of Culture and Sports of the Government of Spain, grant number 45/UPB/20. A.E. is a recipient of a grant of the Basque Government (Eusko Jaurlaritza), grant number PRE_2019_1_0373. D.J.-P. is supported by a grant from the Spanish Ministry of Science and Innovation-MINECO, grant number RYC-2014-16938

Impact of COVID-19 Confinement on Physical Activity and Sedentary Behaviour in Spanish University Students: Role of Gender

[EN] During the COVID-19 pandemic, entire populations were instructed to live in home-confinement to prevent the expansion of the disease. Spain was one of the countries with the strictest conditions, as outdoor physical activity was banned for nearly two months. This study aimed to analyse the changes in physical activity and sedentary behaviours in Spanish university students before and during the confinement by COVID-19 with special focus on gender. We also analysed enjoyment, the tools used and motivation and impediments for doing physical activity. An online questionnaire, which included the International Physical Activity Questionnaire Short Form and certain "ad hoc" questions, was designed. Students were recruited by distributing an invitation through the administrative channels of 16 universities and a total of 13,754 valid surveys were collected. Overall, university students reduced moderate (-29.5%) and vigorous (-18.3%) physical activity during the confinement and increased sedentary time (+52.7%). However, they spent more time on high intensity interval training (HIIT) (+18.2%) and mind-body activities (e.g., yoga) (+80.0%). Adaptation to the confinement, in terms of physical activity, was handled better by women than by men. These results will help design strategies for each gender to promote physical activity and reduce sedentary behaviour during confinement periods.S

Drought Sensitiveness on Forest Growth in Peninsular Spain and the Balearic Islands

Drought is one of the key natural hazards impacting net primary production and tree growth in forest ecosystems. Nonetheless, tree species show different responses to drought events, which make it difficult to adopt fixed tools for monitoring drought impacts under contrasting environmental and climatic conditions. In this study, we assess the response of forest growth and a satellite proxy of the net primary production (NPP) to drought in peninsular Spain and the Balearic Islands, a region characterized by complex climatological, topographical, and environmental characteristics. Herein, we employed three different indicators based on in situ measurements and satellite image-derived vegetation information (i.e., tree-ring width, maximum annual greenness, and an indicator of NPP). We used seven different climate drought indices to assess drought impacts on the tree variables analyzed. The selected drought indices include four versions of the Palmer Drought Severity Index (PDSI, Palmer Hydrological Drought Index (PHDI), Z-index, and Palmer Modified Drought Index (PMDI)) and three multi-scalar indices (Standardized Precipitation Evapotranspiration Index (SPEI), Standardized Precipitation Index (SPI), and Standardized Precipitation Drought Index (SPDI)). Our results suggest that—irrespective of drought index and tree species—tree-ring width shows a stronger response to interannual variability of drought, compared to the greenness and the NPP. In comparison to other drought indices (e.g., PDSI), and our results demonstrate that multi-scalar drought indices (e.g., SPI, SPEI) are more advantageous in monitoring drought impacts on tree-ring growth, maximum greenness, and NPP. This finding suggests that multi-scalar indices are more appropriate for monitoring and modelling forest drought in peninsular Spain and the Balearic Islands

Doñana, diversidad y ciencia

144 páginasLa biodiversidad es más que la suma de los elementos que componen el mundo vivo; también son biodiversidad las relaciones entre esos elementos, los procesos ecológicos que hacen posible su existencia y los procesos evolutivos que los han originado. […] Los seres humanos necesitamos a la biodiversidad más que ella a nosotros, ya que es la responsable de que la Tierra funcione de una manera satisfactoria. […] El entramado de la vida se ocupa de regular la composición de la atmósfera (y con ella, el clima), de depurar el aire y el agua, de hacer fértil al suelo, de evitar riadas y avalanchas, de polinizar las cosechas, de reducir las plagas, etc. Por todo ello es indispensable conservar la biodiversidad, hoy amenazada.” (Miguel Delibes) Doñana, diversidad y ciencia es un paseo conceptual por el espacio natural más emblemático de Europa. La esencia de un mito a través de decenas de fotografías… Un acercamiento respetuoso a la diversidad de sus conceptos, un paseo por la esencia de su historia y una curiosa aproximación a la ciencia que genera hoy en día. En este recorrido descubriremos el carácter distintivo de algunos de los parajes de la reserva, sus matices más interesantes, las texturas y las formas más sorprendentes de la naturaleza, sus colores y conjuntos, sus transformaciones en las últimas décadas y la influencia de la presencia humana en el privilegiado ecosistema de la Reserva Biológica de Doñana

Targeting NAE1-mediated protein hyper-NEDDylation halts cholangiocarcinogenesis and impacts on tumor-stroma crosstalk in experimental models.

[EN] BACKGROUND & AIMS: Cholangiocarcinoma (CCA) comprises a heterogeneous group of malignant tumors associated with dismal prognosis. Alterations in post-translational modifications (PTMs), including NEDDylation, result in abnormal protein dynamics, cell disturbances and disease. Herein, we investigate the role of NEDDylation in CCA development and progression. METHODS: Levels and functions of NEDDylation, together with response to pevonedistat (NEDDylation inhibitor) or CRISPR/Cas9 against NAE1 were evaluated invitro, invivo and/or in patients with CCA. The development of preneoplastic lesions in Nae1+/- mice was investigated using an oncogene-driven CCA model. The impact of NEDDylation in CCA cells on tumor-stroma crosstalk was assessed using CCA-derived cancer-associated fibroblasts (CAFs). Proteomic analyses were carried out by mass-spectrometry. RESULTS: The NEDDylation machinery was found overexpressed and overactivated in human CCA cells and tumors. Most NEDDylated proteins found upregulated in CCA cells, after NEDD8-immunoprecipitation and further proteomics, participate in the cell cycle, proliferation or survival. Genetic (CRISPR/Cas9-NAE1) and pharmacological (pevonedistat) inhibition of NEDDylation reduced CCA cell proliferation and impeded colony formation invitro. NEDDylation depletion (pevonedistat or Nae1+/- mice) halted tumorigenesis in subcutaneous, orthotopic, and oncogene-driven models of CCA invivo. Moreover, pevonedistat potentiated chemotherapy-induced cell death in CCA cells invitro. Mechanistically, impaired NEDDylation triggered the accumulation of both cullin RING ligase and NEDD8 substrates, inducing DNA damage and cell cycle arrest. Furthermore, impaired NEDDylation in CCA cells reduced the secretion of proteins involved in fibroblast activation, angiogenesis, and oncogenic pathways, ultimately hampering CAF proliferation and migration. CONCLUSION: Aberrant protein NEDDylation contributes to cholangiocarcinogenesis by promoting cell survival and proliferation. Moreover, NEDDylation impacts the CCA-stroma crosstalk. Inhibition of NEDDylation with pevonedistat may represent a potential therapeutic strategy for patients with CCA. LAY SUMMARY: Little is known about the role of post-translational modifications of proteins in cholangiocarcinoma development and progression. Herein, we show that protein NEDDylation is upregulated and hyperactivated in cholangiocarcinoma, promoting tumor growth. Pharmacological inhibition of NEDDylation halts cholangiocarcinogenesis and could be an effective therapeutic strategy to tackle these tumors.This article is based upon work from the COST Action CA18122 European Cholangiocarcinoma Network supported by COST (European Cooperation in Science and Technology: www.cost.eu)

Adult Prevalence of Epilepsy in Spain: EPIBERIA, a Population-Based Study

Background. This study assesses the lifetime and active prevalence of epilepsy in Spain in people older than 18 years. Methods. EPIBERIA is a population-based epidemiological study of epilepsy prevalence using data from three representative Spanish regions (health districts in Zaragoza, Almería, and Seville) between 2012 and 2013. The study consisted of two phases: screening and confirmation. Participants completed a previously validated questionnaire (EPIBERIA questionnaire) over the telephone. Results. A total of 1741 valid questionnaires were obtained, including 261 (14.99%) raising a suspicion of epilepsy. Of these suspected cases, 216 (82.75%) agreed to participate in phase 2. Of the phase 2 participants, 22 met the International League Against Epilepsy’s diagnostic criteria for epilepsy. The estimated lifetime prevalence, adjusted by age and sex per 1,000 people, was 14.87 (95% CI: 9.8–21.9). Active prevalence was 5.79 (95% CI: 2.8–10.6). No significant age, sex, or regional differences in prevalence were detected. Conclusions. EPIBERIA provides the most accurate estimate of epilepsy prevalence in the Mediterranean region based on its original methodology and its adherence to ILAE recommendations. We highlight that the lifetime prevalence and inactive epilepsy prevalence figures observed here were compared to other epidemiological studies

Izaña Atmospheric Research Center. Activity Report 2019-2020

Editors: Emilio Cuevas, Celia Milford and Oksana Tarasova.[EN]The Izaña Atmospheric Research Center (IARC), which is part of the State Meteorological Agency of Spain (AEMET), is a site of excellence in atmospheric science. It manages four observatories in Tenerife including the high altitude Izaña Atmospheric Observatory. The Izaña Atmospheric Observatory was inaugurated in 1916 and since that date has carried out uninterrupted meteorological and climatological observations, contributing towards a unique 100-year record in 2016. This reports are a summary of the many activities at the Izaña Atmospheric Research Center to the broader community. The combination of operational activities, research and development in state-of-the-art measurement techniques, calibration and validation and international cooperation encompass the vision of WMO to provide world leadership in expertise and international cooperation in weather, climate, hydrology and related environmental issues.[ES]El Centro de Investigación Atmosférica de Izaña (CIAI), que forma parte de la Agencia Estatal de Meteorología de España (AEMET), representa un centro de excelencia en ciencias atmosféricas. Gestiona cuatro observatorios en Tenerife, incluido el Observatorio de Izaña de gran altitud, inaugurado en 1916 y que desde entonces ha realizado observaciones meteorológicas y climatológicas ininterrumpidas y se ha convertido en una estación centenaria de la OMM. Estos informes resumen las múltiples actividades llevadas a cabo por el Centro de Investigación Atmosférica de Izaña. El liderazgo del Centro en materia de investigación y desarrollo con respecto a las técnicas de medición, calibración y validación de última generación, así como la cooperación internacional, le han otorgado una reputación sobresaliente en lo que se refiere al tiempo, el clima, la hidrología y otros temas ambientales afines