359 research outputs found

    Generation of periventricular reactive astrocytes overexpressing aquaporin 4 Is stimulated by mesenchymal stem cell therapy

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    Aquaporin-4 (AQP4) plays a crucial role in brain water circulation and is considered a therapeutic target in hydrocephalus. Congenital hydrocephalus is associated with a reaction of astrocytes in the periventricular white matter both in experimental models and human cases. A previous report showed that bone marrow-derived mesenchymal stem cells (BM-MSCs) transplanted into the lateral ventricles of hyh mice exhibiting severe congenital hydrocephalus are attracted by the periventricular astrocyte reaction, and the cerebral tissue displays recovery. The present investigation aimed to test the effect of BM-MSC treatment on astrocyte reaction formation. BM-MSCs were injected into the lateral ventricles of four-day-old hyh mice, and the periventricular reaction was detected two weeks later. A protein expression analysis of the cerebral tissue differentiated the BM-MSC-treated mice from the controls and revealed effects on neural development. In in vivo and in vitro experiments, BM-MSCs stimulated the generation of periventricular reactive astrocytes overexpressing AQP4 and its regulatory protein kinase D-interacting substrate of 220 kDa (Kidins220). In the cerebral tissue, mRNA overexpression of nerve growth factor (NGF), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 (HIF1α), and transforming growth factor beta 1 (TGFÎČ1) could be related to the regulation of the astrocyte reaction and AQP4 expression. In conclusion, BM-MSC treatment in hydrocephalus can stimulate a key developmental process such as the periventricular astrocyte reaction, where AQP4 overexpression could be implicated in tissue recovery.The present work was supported by grants PI15/00619 and PI19/00778 (to A.J.J. and P.P.-G.), PI21/000914 (to J.V.) and PI21/000915 (to A.G.) from the Instituto de Salud Carlos III, Spain, co-financed by FEDER funds from the European Union; PI18-RT-2233 from Junta de AndalucĂ­a (to A.G.) co-financed by Programa Operativo FEDER 2014–2020; PID2020-115218RB-I00 to T.I., funded by MCIN/AEI/10.13039/501100011033; Centro de InvestigaciĂłn BiomĂ©dica en Red de Enfermedades Neurodegenerativas (CIBERNED, Instituto de Salud Carlos III, Spain) to J.V., T.I. and A.G.; FPU13/02906 to MG-B from the Ministerio de EducaciĂłn, Cultura y Deporte, Spain; RYC-2014-16980 to P.P.-G. from the Ministerio de EconomĂ­a y Competitividad, Spain; UMA18-FEDERJA-277 from Plan Operativo FEDER AndalucĂ­a 2014–2020 and Universidad de MĂĄlaga to P.P.-G.; Proyectos dirigidos por jĂłvenes investigadores from Universidad de MĂĄlaga to P.P.-G. The cost of this publication has been paid in art by “ERDF A way of making Europe” funds. Partial funding for open access charge: Universidad de MĂĄlaga

    Amplifying actions for food system transformation: Insights from the Stockholm region

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    Food is essential to people and is one of the main ways in which people are connected to the world’s ecosystems. However, food systems often cause ecosystem degradation and produce ill-health, which has generated increasing calls to transform food systems to be more sustainable. The Swedish food system is currently undergoing substantial change. A varied set of local actors have created alternative sustainability initiatives that enact new ways of doing, thinking, and organizing. These actors can increase the transformative impact of their initiatives through multiple actions and a variety of amplification processes. We analyzed the actions adopted by 29 food initiatives active in the Stockholm region using information available online. We conducted 11 interviews to better understand the amplification processes of speeding up (i.e., accelerating impact), scaling up (i.e., influencing higher institutional levels), and scaling deep (i.e., changing values and mind-sets). Our results indicated that the initiatives mainly seek to stabilize and grow their impact while changing the awareness, values, and mind-sets of people concerning the food they consume (scaling deep). However, these approaches raise new questions about whether these actions subvert or reinforce current unsustainable and inequitable system dynamics. We suggest there are distinct steps that local and regional governments could take to support these local actors via collaborations with coordinated forms of initiatives, and fostering changes at the municipality level, but these steps require ongoing, adaptive approaches given the highly complex nature of transformative change and the risks of reinforcing current system dynamics

    The morphometric acclimation to depth explains the long-term resilience of the seagrass Cymodocea nodosa in a shallow tidal lagoon

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    Cadiz Bay is a shallow mesotidal lagoon with extensive populations of the seagrass Cymodocea nodosa at intertidal and shallow subtidal elevations. This work aims to understand the mechanisms behind the resilience of this species to gradual sea level rise by studying its acclimation capacity to depth along the shallow littoral, and therefore, to gradual variations in the light environment. To address this objective, these populations have been monitored seasonally over a 10 year period, representing the longest seasonal database available in the literature for this species. The monitoring included populations at 0.4, -0.08 and -0.5 m LAT. The results show that C. nodosa has a strong seasonality for demographic and shoot dynamic properties - with longer shoots and larger growth in summer (high temperature) than in winter (low temperature), but also some losses. Moreover, shoots have different leaf morphometry depending on depth, with small and dense shoots in the intertidal areas (0.4 m) and sparse large shoots in the subtidal ones (-0.08 and 0.5 m). These differences in morphometry and shoot dynamic properties, combined with the differences in shoot density, explain the lack of differences in meadow production balance (i.e. meadow growth - meadow losses) between the intertidal (0.4 m) and the deepest population (-0.5 m), supporting the long term resilience of Cymodocea nodosa in Cadiz Bay. This study contributes to the understanding of the mechanisms behind seagrass stability and resilience, which is particularly important towards predicting the effects of climate change on these key coastal ecosystems, and also highlights the value of continuous long-term monitoring efforts to evaluate seagrass trajectories

    Isolation, Characterization and Lipid-Binding Properties of the Recalcitrant FtsA Division Protein from Escherichia coli

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    We have obtained milligram amounts of highly pure Escherichia coli division protein FtsA from inclusion bodies with an optimized purification method that, by overcoming the reluctance of FtsA to be purified, surmounts a bottleneck for the analysis of the molecular basis of FtsA function. Purified FtsA is folded, mostly monomeric and interacts with lipids. The apparent affinity of FtsA binding to the inner membrane is ten-fold higher than to phospholipids, suggesting that inner membrane proteins could modulate FtsA-membrane interactions. Binding of FtsA to lipids and membranes is insensitive to ionic strength, indicating that a net contribution of hydrophobic interactions is involved in the association of FtsA to lipid/membrane structures

    Boundary condition model for the simulation of organic solar cells

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    (c) 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/http://www.sciencedirect.com/science/article/pii/S1566119917302434Organic solar cells (OSCs) are promising photovoltaic devices to convert solar energy into electrical energy. Their many advantages such as lightweight, flexibility and low manufacturing costs are intrinsic to the organic/polymeric technology. However, because the performance of OSCs is still not competitive with inorganic solar cells, there is urgent need to improve the device performance using better designs, technologies and models. In this work, we focus on the developing an accurate physics-based model that relates the charge carrier density at the metal-organic boundaries with the current density in OSCs using our previous studies on single-carrier and bipolar diodes. The model for the boundary condition of the charge carrier density at the interfaces of OSCs follows a power-law function with the current density, both in dark and under illumination, and simulated current-voltage characteristics are verified with experimental results. The numerical simulations of the current-voltage characteristics of OSCs consider well-established models for the main physical and optical processes that take place in the device: light absorption and generation of excitons, dissociation of excitons into free charge carriers, charge transport, recombination and injection-extraction of free carriers. Our analysis provides important insights on the influence of the metal-organic interfaces on the overall performance of OSCs. The model is also used to explain the anomalous S-shape current-voltage curves found in some experimental data.This work was supported by Ministerio de EducaciĂłn y Ciencia under research Grant FPU12/02712 and MINECO/FEDER under research Project MAT2016-76892-C3-3-R, and the Canada Research Chair program, NSERC ResEau strategic network and the NCE IC-IMPACTS

    Quantifying and mapping species threat abatement opportunitiesto support national target setting

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    The successful implementation of the Convention on Biological Diversity’s post-2020Global Biodiversity Framework will rely on effective translation of targets from global tonational level and increased engagement across diverse sectors of society. Species conserva-tion targets require policy support measures that can be applied to a diversity of taxonomicgroups, that link action targets to outcome goals, and that can be applied to both global andnational data sets to account for national context, which the species threat abatement andrestoration (STAR) metric does. To test the flexibility of STAR, we applied the metric to vascular plants listed on national red lists of Brazil, Norway, and South Africa. The STARmetric uses data on species’ extinction risk, distributions, and threats, which we obtainedfrom national red lists to quantify the contribution that threat abatement and habitatrestoration activities could make to reducing species’ extinction risk. Across all 3 coun-tries, the greatest opportunity for reducing plant species’ extinction risk was from abatingthreats from agricultural activities, which could reduce species’ extinction risk by 54% inNorway, 36% in South Africa, and 29% in Brazil. Species extinction risk could be reducedby a further 21% in South Africa by abating threats from invasive species and by 21% inBrazil by abating threats from urban expansion. Even with different approaches to red-listing among countries, the STAR metric yielded informative results that identified wherethe greatest conservation gains could be made for species through threat-abatement andrestoration activities. Quantifiably linking local taxonomic coverage and data collection toglobal processes with STAR would allow national target setting to align with global targetsand enable state and nonstate actors to measure and report on their potential contributionsto species conservation. habitat restoration, national red lists, species’ extinction risk, threat reduction, threatened species, vascular plantspublishedVersio

    Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn’s Disease Patients: The SUSTAIN Study

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    Background Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn’s disease (CD) patients in real-world clinical practice. Methods A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≄1 intravenous dose of ustekinumab for ≄6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. Results A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≄3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≄1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). Conclusions Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice
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