The adaptation of lipid profile of human fibroblasts to alginate 2D films and 3D printed scaffolds

Background: The investigation of the interactions between cells and active materials is pivotal in the emerging 3D printing-biomaterial application fields. Here, lipidomics has been used to explore the early impact of alginate (ALG) hydrogel architecture (2D films or 3D printed scaffolds) and the type of gelling agent (CaCl2 or FeCl3) on the lipid profile of human fibroblasts. Methods: 2D and 3D ALG scaffolds were prepared and characterized in terms of water content, swelling, mechanical resistance and morphology before human fibroblast seeding (8 days). Using a liquid chromatography-triple quadrupole-tandem mass spectrometry approach, selected ceramides (CER), lysophosphatidylcholines (LPC), lysophosphatidic acids (LPA) and free fatty acids (FFA) were analyzed. Results: The results showed a clear alteration in the CER expression profile depending of both the geometry and the gelling agent used to prepare the hydrogels. As for LPCs, the main parameter affecting their distribution is the scaffold architecture with a significant decrease in the relative expression levels of the species with higher chain length (C20 to C22) for 3D scaffolds compared to 2D films. In the case of FFAs and LPAs only slight differences were observed as a function of scaffold geometry or gelling agent. Conclusions: Variations in the cell membrane lipid profile were observed for 3D cell cultures compared to 2D and these data are consistent with activation processes occurring through the mutual interactions between fibroblasts and ALG support. These unknown physiologically relevant changes add insights into the discussion about the relationship between biomaterial and the variations of cell biological functions

Green balance in urban areas as an indicator for policy support: a multi-level application

Green spaces are increasingly recognised as key elements in enhancing urban resilience as they provide several ecosystem services. Therefore, their implementation and monitoring in cities are crucial to meet sustainability targets. In this paper, we provide a methodology to compute an indicator that assesses changes in vegetation cover within Urban Green Infrastructure (UGI). Such an indicator is adopted as one of the indicators for reporting on the key area “nature and biodiversity” in the Green City Accord (GCA). In the first section, the key steps to derive the indicator are described and a script, which computes the trends in vegetation cover using Google Earth Engine (GEE), is provided. The second section describes the application of the indicator in a multi-scale, policy-orientated perspective. The analysis has been carried out in 696 European Functional Urban Areas (FUAs), considering changes in vegetation cover inside UGI between 1996 and 2018. Results were analysed for the EU and the United Kingdom. The Municipality of Padua (Italy) is used as a case study to illustrate the results at the local level. Over the last 22 years, a slight upward trend characterised the vegetation growth within UGI in European FUAs. Within core cities and densily built-upcommuting zones, the trend was stable; in non-densely built-up areas, an upward trend was recorded. Vegetation cover in UGI has been relatively stable in European cities. However, a negative balance between abrupt changes in greening and browning has been recorded, affecting most parts of European cities (75% of core cities and 77% of commuting zones in densely built-up areas). This still indicates ongoing land take with no compensation of green spaces that are lost to artificial areas. Focusing on the FUA of Padua, a downward trend was observed in 33.3% and 12.9% of UGI in densely built-up and not-densely built-up areas, respectively. Within the FUA of Padua, most municipalities are characterised by a negative balance between abrupt greening and browning, both in non-densely built-up and densely built-up areas. This approach complements traditional metrics, such as the extent of UGI or tree canopy cover, by providing a valuable measure of condition of urban ecosystems and an instrument to monitor the impact of land take

Urban heat island mitigation by green infrastructure in European Functional Urban Areas

The Urban Heat Island (UHI) effect is one of the most harmful environmental hazards for urban dwellers. Climate change is expected to increase the intensity of the UHI effect. In this context, the implementation of Urban Green Infrastructure (UGI) can partially reduce UHI intensity, promoting a resilient urban environment and contributing to climate change adaptation and mitigation. In order to achieve this result, there is a need to systematically integrate UGI into urban planning and legislation, but this process is subject to the availability of widely applicable, easily accessible and quantitative evidence. To offer a big picture of urban heat intensity and opportunities to mitigate high temperatures, we developed a model that reports the Ecosystem Service (ES) of microclimate regulation of UGI in 601 European cities. The model simulates the temperature difference between a baseline and a no-vegetation scenario, extrapolating the role of UGI in mitigating UHI in different urban contexts. Finally, a practical, quantitative indicator that can be applied by policymakers and city administrations has been elaborated, allowing to estimate the amount of urban vegetation that is needed to cool summer temperatures by a certain degree. UGI is found to cool European cities by 1.07 °C on average, and up to 2.9 °C, but in order to achieve a 1 °C drop in urban temperatures, a tree cover of at least 16% is required. The microclimate regulation ES is mostly dependent on the amount of vegetation inside a city and by transpiration and canopy evaporation. Furthermore, in almost 40% of the countries, more than half of the residing population does not benefit from the microclimate regulation service provided by urban vegetation. Widespread implementation of UGI, in particular in arid regions and cities with insufficient tree cover, is key to ensure healthy urban living conditions for citizens

BiodiverCities: A roadmap to enhance the biodiversity and green infrastructure of European cities by 2030

BiodiverCities is a European Parliament Pilot Project, developed with the aim of enhancing the use of Urban Green Infrastructure (UGI) to enhance the condition of urban ecosystems, providing benefits for people and nature. In this report, an evaluation around the most appropriate reporting unit for an urban ecosystems assessment is carried out, comparing Functional Urban Areas (FUA) and Local Administrative Units (LAU). Furthermore, UGI are assessed from a multi-scale perspective. The status and scenarios of UGI in European urbanised areas is first analysed measuring the urban green areas and the tree canopy cover. Secondly, the contribution of UGI to the overall European Green Infrastructure (EU-GI) is quantified, evaluating the respective role of FUA and LAU. Finally, the effect of urban characteristics on biotic homogenization is analysed exploring how urbanised areas impact on avian population and communities in French cities. The results of this study will inform the development of a roadmap for greening cities in Europe in the 2020-2030 decade

Urban Ecosystem accounts following the SEEA EA standard: A pilot application in Europe

National and local authorities are promoting restoration actions in urban areas to mitigate societal challenges such as urban heat island, poor air quality or biodiversity loss. Urban re-greening is among the implementation actions supporting targets of the European Green Deal, EU Biodiversity Strategy 2030, its proposal for a Nature Restoration Law, and the proposal for an amendment of the Regulation on Environmental Accounts. However, to monitor progress towards policy targets and an overall enhancement of urban ecosystems, policy makers require regular, consistent and comparable data. The implementation of United Nation's System of Environmental Economic Accounting - Ecosystem Accounting (SEEA EA) on urban ecosystems could help to track changes in their ecosystem extent, condition, services and derived benefits. Despite SEEA EA became a statistical standard, it has been only tested in pilot exercises, of which very few are urban ecosystem accounts. This report presents a pilot SEEA EA urban ecosystem account for EU-27 and EFTA Member States in 2018. It discusses challenges for the development of urban ecosystem accounts and potential solutions. The outputs illustrate where re-greening efforts should be applied and discusses feasibility and potential issues of targets. The report also presents key insights to operationalise SEEA EA for urban ecosystem accounts. It provides an instructive guiding example to national and local authorities starting to draft their own urban ecosystem accounts

Use of ultrasonography to discriminate psoriatic arthritis from fibromyalgia: A post‐hoc analysis of the ulisse study

In psoriatic arthritis (PsA) patients with concomitant chronic widespread pain, the differential diagnosis with fibromyalgia syndrome (FMS) can be challenging. We evaluated whether ultrasound (US) examination of entheseal sites can distinguish pain from (PsA) enthesitis versus FMS. PsA and FMS patients underwent clinical evaluation and gray‐scale (GS; B‐mode) and power Doppler (PD) US examination of the entheses. At least one enthesis with GS‐ and PD‐mode changes was found in 90% and 59.3% of PsA patients (n = 140) and 62.7% and 35.3% of FMS patients (n = 51), respectively. GS and PD identified changes in 49.5% and 19.2% of the 840 PsA entheses and 22.5% and 7.9% of the 306 FMS entheses, respectively. Receiver operating characteristic curve analysis showed an area under the curve of 0.77 and 0.66 for B‐ and PD‐mode, respectively, 3.5 being the best cut‐off GS‐score to discriminate the two conditions. Multivariate regression showed that Achilles and proximal patellar tendon enthesitis (B‐mode) were strongly associated with PsA (odds ratio, ~2). Principal component analysis (B‐mode) confirmed that PsA patients have a higher number of involved entheses and patterns of entheseal involvement than FMS patients. US evaluation of the entheses may help differentiate chronic widespread pain from PsA versus FMS

Mapping and assessment of ecosystems and their services. Urban ecosystems

Action 5 of the EU Biodiversity Strategy to 2020 requires member states to Map and Assess the state of Ecosystems and their Services (MAES). This report provides guidance for mapping and assessment of urban ecosystems. The MAES urban pilot is a collaboration between the European Commission, the European Environment Agency, volunteering Member States and cities, and stakeholders. Its ultimate goal is to deliver a knowledge base for policy and management of urban ecosystems by analysing urban green infrastructure, condition of urban ecosystems and ecosystem services. This report presents guidance for mapping urban ecosystems and includes an indicator framework to assess the condition of urban ecosystems and urban ecosystem services. The scientific framework of mapping and assessment is designed to support in particular urban planning policy and policy on green infrastructure at urban, metropolitan and regional scales. The results are based on the following different sources of information: a literature survey of 54 scientific articles, an online-survey (on urban ecosystems, related policies and planning instruments and with participation of 42 cities), ten case studies (Portugal: Cascais, Oeiras, Lisbon; Italy: Padua, Trento, Rome; The Netherlands: Utrecht; Poland: Poznań; Spain: Barcelona; Norway: Oslo), and a two-day expert workshop. The case studies constituted the core of the MAES urban pilot. They provided real examples and applications of how mapping and assessment can be organized to support policy; on top, they provided the necessary expertise to select a set of final indicators for condition and ecosystem services. Urban ecosystems or cities are defined here as socio-ecological systems which are composed of green infrastructure and built infrastructure. Urban green infrastructure (GI) is understood in this report as the multi-functional network of urban green spaces situated within the boundary of the urban ecosystem. Urban green spaces are the structural components of urban GI. This study has shown that there is a large scope for urban ecosystem assessments. Firstly, urban policies increasingly use urban green infrastructure and nature-based solutions in their planning process. Secondly, an increasing amount of data at multiple spatial scales is becoming available to support these policies, to provide a baseline, and to compare or benchmark cities with respect to the extent and management of the urban ecosystem. Concrete examples are given on how to delineate urban ecosystems, how to choose an appropriate spatial scale, and how to map urban ecosystems based on a combination of national or European datasets (including Urban Atlas) and locally collected information (e.g., location of trees). Also examples of typologies for urban green spaces are presented. This report presents an indicator framework which is composed of indicators to assess for urban ecosystem condition and for urban ecosystem services. These are the result of a rigorous selection process and ensure consistent mapping and assessment across Europe. The MAES urban pilot will continue with work on the interface between research and policy. The framework presented in this report needs to be tested and validated across Europe, e.g. on its applicability at city scale, on how far the methodology for measuring ecosystem condition and ecosystem service delivery in urban areas can be used to assess urban green infrastructure and nature-based solutions

Exenatide regulates pancreatic islet integrity and insulin sensitivity in the nonhuman primate baboon Papio hamadryas.

The glucagon-like peptide-1 receptor agonist exenatide improves glycemic control by several and not completely understood mechanisms. Herein, we examined the effects of chronic intravenous exenatide infusion on insulin sensitivity, β cell and α cell function and relative volumes, and islet cell apoptosis and replication in nondiabetic nonhuman primates (baboons). At baseline, baboons received a 2-step hyperglycemic clamp followed by an l-arginine bolus (HC/A). After HC/A, baboons underwent a partial pancreatectomy (tail removal) and received a continuous exenatide (n = 12) or saline (n = 12) infusion for 13 weeks. At the end of treatment, HC/A was repeated, and the remnant pancreas (head-body) was harvested. Insulin sensitivity increased dramatically after exenatide treatment and was accompanied by a decrease in insulin and C-peptide secretion, while the insulin secretion/insulin resistance (disposition) index increased by about 2-fold. β, α, and δ cell relative volumes in exenatide-treated baboons were significantly increased compared with saline-treated controls, primarily as the result of increased islet cell replication. Features of cellular stress and secretory dysfunction were present in islets of saline-treated baboons and absent in islets of exenatide-treated baboons. In conclusion, chronic administration of exenatide exerts proliferative and cytoprotective effects on β, α, and δ cells and produces a robust increase in insulin sensitivity in nonhuman primates

Contrasting requirements during disease evolution identify EZH2 as a therapeutic target in AML

Epigenetic regulators, such as EZH2, are frequently mutated in cancer, and loss-of-function EZH2 mutations are common in myeloid malignancies. We have examined the importance of cellular context for Ezh2 loss during the evolution of acute myeloid leukemia (AML), where we observed stage-specific and diametrically opposite functions for Ezh2 at the early and late stages of disease. During disease maintenance, WT Ezh2 exerts an oncogenic function that may be therapeutically targeted. In contrast, Ezh2 acts as a tumor suppressor during AML induction. Transcriptional analysis explains this apparent paradox, demonstrating that loss of Ezh2 derepresses different expression programs during disease induction and maintenance. During disease induction, Ezh2 loss derepresses a subset of bivalent promoters that resolve toward gene activation, inducing a feto-oncogenic program that includes genes such as Plag1, whose overexpression phenocopies Ezh2 loss to accelerate AML induction in mouse models. Our data highlight the importance of cellular context and disease phase for the function of Ezh2 and its potential therapeutic implications.The Huntly laboratory is funded by CRUK (program C18680/ A25508), the European Research Council (grant 647685 COMAL), the Kay Kendall Leukaemia Fund, the Medical Research Council (MRC), Bloodwise, the Wellcome Trust, and the Cambridge National Institute of Health Research Biomedical Research Centre. F. Basheer is a recipient of a Wellcome Trust PhD for Clinicians award. P. Gallipoli is funded by the Wellcome Trust (109967/Z/15/Z). We acknowledge the Wellcome Trust/ MRC center grant (097922/Z/11/Z) and support from Wellcome Trust strategic award 100140. Research in the laboratory is also supported by core funding from the Wellcome Trust and MRC to the Wellcome-MRC Cambridge Stem Cell Institute. This research was supported by the Cambridge National Institute of Health Research Biomedical Research Centre Cell Phenotyping Hub

EU-wide methodology to map and assess ecosystem condition

The EU Biodiversity Strategy for 2030 calls for developing an EU-wide methodology to map, assess and achieve good condition of ecosystems, so they can deliver benefits to society through the provision of ecosystem services. The EU-wide methodology presented in this report addresses this methodological gap. The EU-wide methodology has adopted the System of Environmental Economic Accounting - Ecosystem Accounting (SEEA EA) as reference framework. The SEEA EA is an integrated framework for organizing biophysical information about ecosystems, adopted as a global statistical standard by the United Nations. The SEEA EA is also the reference framework under the proposal for the amendment of Regulation (EU) No 691/2011 on European environmental economic accounts. Building on previous work done within the MAES initiative, the EU-wide methodology presents useful insights to operationalise the SEEA EA at EU level by integrating different EU data streams in a consistent way with this global statistical standard to consistently map and assess ecosystem condition in the EU across all ecosystem types. The adoption of the SEEA EA framework offers the flexibility to integrate different data flows, leveraging the use of available EU data, such as data reported by MS under EU legislation and EU geospatial data. The EU-wide methodology. The implementation of the EU-wide methodology, making use of available data, will provide the scientific knowledge base to support a range of policies and legal instruments