Promoting ecological solutions for sustainable infrastructure

Sustainable infrastructure needs ecological solutions – it’s time to work together! We, the participants of the IENE 2020 International Conference, acknowledge that: 1. We are facing a significant worldwide expansion of transportation networks; this is especially the case in countries with developing economies. 2. If no action is taken, this global expansion will entail a substantial increase in greenhouse gas emissions, wildlife mortality and landscape fragmentation and change, with devastating effects on climate, biodiversity and ecosystem services. 3. Globally, ecosystem services are estimated to yield more than the Gross World Product of 2019 (https://www.worldometers.info/gdp/). 4. Despite the development and implementation of environmental impact assessment legislation, many existing transportation infrastructure networks are not environmentally friendly. These impacts are far-reaching with a debt being paid daily through unnecessary risks extendable to human health and well-being. 5.The economic, social, and ecological consequences of biodiversity loss and the role of transportation infrastructure is increasingly acknowledged worldwide: •Conservation and restoration of ecological connectivity is a major flagship in the preparation of the upcoming United Nations “Post-2020 Global biodiversity framework” following the recognised failure of the Aichi Targets associated with the loss and fragmentation of natural habitats (Target 5) (https://www.cbd.int/gbo5). •The European Green Deal and the new European Biodiversity Strategy for 2030, adopted by the European Commission in May 2020, stresses the need to develop a resilient Trans-European Nature Network supported by ecological corridors allowing the free flow of genes and individuals (https://ec.europa.eu/info/sites/info/files/communication-annex-eu-biodiversity-strategy-2030_en.pdf). •The Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES) states that since 1970, transportation infrastructure is an important driver of land use change and associated loss of terrestrial biodiversity (https://ipbes.net/global-assessment). •The World Economic Forum 2020 recognised that biodiversity loss is one of the major threats with ‘plausible higher than average impact’ on Global Economies (https://www.weforum.org/reports/the-global-risks-report-2020). 6.To ahieve sustainability, infrastructure development must be decoupled from its negative effect on biodiversity. This requires immediate, stringent action and shared responsibilities from all stakeholders. 7.Regional, national, and worldwide networks of experts, including researchers, practitioners, landscape designers, and managers, address such concerns through knowledge-sharing platforms that promote effective ecological solutions. 8.The scarcity of collective and coordinated efforts, such as joint decision-making processes involving environmental, transportation, energy, policy and financing agencies, is still a major obstacle to achieve sustainability in transportation infrastructure projects.Comissão Europeia. Programa LIFE. Projeto LIFE LINES (LIFE14 NAT/PT/001081

Binding of Estrogenic Compounds to Recombinant Estrogen Receptor-α: Application to Environmental Analysis

Estrogenic activity in environmental samples could be mediated through a wide variety of compounds and by various mechanisms. High-affinity compounds for estrogen receptors (ERs), such as natural or synthetic estrogens, as well as low-affinity compounds such as alkylphenols, phthalates, and polychlorinated biphenyls are present in water and sediment samples. Furthermore, compounds such as polycyclic aromatic hydrocarbons, which do not bind ERs, modulate estrogen activity by means of the aryl hydrocarbon receptor (AhR). In order to characterize compounds that mediate estrogenic activity in river water and sediment samples, we developed a tool based on the ER-αligand-binding domain, which permitted us to estimate contaminating estrogenic compound affinities. We designed a simple transactivation assay in which compounds of high affinity were captured by limited amounts of recombinant ER-αand whose capture led to a selective inhibition of transactivation. This approach allowed us to bring to light that water samples contain estrogenic compounds that display a high affinity for ERs but are present at low concentrations. In sediment samples, on the contrary, we showed that estrogenic compounds possess a low affinity and are present at high concentration. Finally, we used immobilized recombinant ER-αto separate ligands for ER and AhR that are present in river sediments. Immobilized ER-α, which does not retain dioxin-like compounds, enabled us to isolate and concentrate ER ligands to facilitate their further analysis

Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation

End-stage liver disease caused by chronic hepatitis C virus (HCV) infection is a leading cause for liver transplantation (LT). Due to viral evasion from host immune responses and the absence of preventive antiviral strategies, reinfection of the graft is universal. The mechanisms by which the virus evades host immunity to reinfect the liver graft are unknown. In a longitudinal analysis of six HCV-infected patients undergoing LT, we demonstrate that HCV variants reinfecting the liver graft were characterized by efficient entry and poor neutralization by antibodies present in pretransplant serum compared with variants not detected after transplantation. Monoclonal antibodies directed against HCV envelope glycoproteins or a cellular entry factor efficiently cross-neutralized infection of human hepatocytes by patient-derived viral isolates that were resistant to autologous host-neutralizing responses. These findings provide significant insights into the molecular mechanisms of viral evasion during HCV reinfection and suggest that viral entry is a viable target for prevention of HCV reinfection of the liver graft

PTCH1+/− Dermal Fibroblasts Isolated from Healthy Skin of Gorlin Syndrome Patients Exhibit Features of Carcinoma Associated Fibroblasts

Gorlin's or nevoid basal cell carcinoma syndrome (NBCCS) causes predisposition to basal cell carcinoma (BCC), the commonest cancer in adult human. Mutations in the tumor suppressor gene PTCH1 are responsible for this autosomal dominant syndrome. In NBCCS patients, as in the general population, ultraviolet exposure is a major risk factor for BCC development. However these patients also develop BCCs in sun-protected areas of the skin, suggesting the existence of other mechanisms for BCC predisposition in NBCCS patients. As increasing evidence supports the idea that the stroma influences carcinoma development, we hypothesized that NBCCS fibroblasts could facilitate BCC occurence of the patients. WT (n = 3) and NBCCS fibroblasts bearing either nonsense (n = 3) or missense (n = 3) PTCH1 mutations were cultured in dermal equivalents made of a collagen matrix and their transcriptomes were compared by whole genome microarray analyses. Strikingly, NBCCS fibroblasts over-expressed mRNAs encoding pro-tumoral factors such as Matrix Metalloproteinases 1 and 3 and tenascin C. They also over-expressed mRNA of pro-proliferative diffusible factors such as fibroblast growth factor 7 and the stromal cell-derived factor 1 alpha, known for its expression in carcinoma associated fibroblasts. These data indicate that the PTCH1+/− genotype of healthy NBCCS fibroblasts results in phenotypic traits highly reminiscent of those of BCC associated fibroblasts, a clue to the yet mysterious proneness to non photo-exposed BCCs in NBCCS patients

Improved clinical investigation and evaluation of high-risk medical devices: the rationale and objectives of CORE-MD (Coordinating Research and Evidence for Medical Devices)

: In the European Union (EU) the delivery of health services is a national responsibility but there are concerted actions between member states to protect public health. Approval of pharmaceutical products is the responsibility of the European Medicines Agency, whereas authorizing the placing on the market of medical devices is decentralized to independent 'conformity assessment' organizations called notified bodies. The first legal basis for an EU system of evaluating medical devices and approving their market access was the medical device directives, from the 1990s. Uncertainties about clinical evidence requirements, among other reasons, led to the EU Medical Device Regulation (2017/745) that has applied since May 2021. It provides general principles for clinical investigations but few methodological details-which challenges responsible authorities to set appropriate balances between regulation and innovation, pre- and post-market studies, and clinical trials and real-world evidence. Scientific experts should advise on methods and standards for assessing and approving new high-risk devices, and safety, efficacy, and transparency of evidence should be paramount. The European Commission recently awarded a Horizon 2020 grant to a consortium led by the European Society of Cardiology and the European Federation of National Associations of Orthopaedics and Traumatology, that will review methodologies of clinical investigations, advise on study designs, and develop recommendations for aggregating clinical data from registries and other real-world sources. The CORE-MD project (Coordinating Research and Evidence for Medical Devices) will run until March 2024; here we describe how it may contribute to the development of regulatory science in Europe

Käthe Kollwitz in Los Angeles 1937

Im Juni 1937 eröffnete Jacob Zeitlin in seiner Buchladen-Galerie in Los Angeles eine Ausstellung mit Grafiken von Käthe Kollwitz. Es war die erste Ausstellung von Kollwitz’ Werk in Südkalifornien. Co-Sponsor der Ausstellung und der glamourösen Vernissage war die Hollywood Anti-Nazi League for the Defense of American Democracy. Die Redner des Abends waren der deutsche Schriftsteller und Aktivist Ernst Toller und der amerikanische Komponist George Antheil. Zu den illustren Gästen gehörten Fritz Lang, Richard Neutra, Arnold Schönberg, George Gershwin, Kurt Weill und andere Berühmtheiten der Filmindustrie und der deutschösterreichischen Exilgemeinde. Die Kollwitz-Ausstellung wurde zum Dreh- und Angelpunkt der zentralen Konfliktfelder der Stadt: Sie war nicht bloß ein kulturelles Ereignis in Zeitlins Buchladen-Galerie, sondern vor allem eine gezielte politische Aktion der Hollywood Anti-Nazi League. Kollwitz’ Schaffen geriet damit ins Kreuzfeuer der Auseinandersetzungen zwischen dem antifaschistischen Kampf der Anti-Nazi League und den gewalttätigen Aktionen nationalsozialistischer Gruppen in Los Angeles. In diesem politischen Spannungsfeld wurde Käthe Kollwitz als »anti-Nazi artist« wahrgenommen und ihrer Ausstellung eine aktive Rolle im Kampf gegen Hitler zugeschrieben. Die Kapitel des Buches zeichnen nach, wie die Ausstellung zum Kreuzungspunkt von vier Biografien wurde: Käthe Kollwitz, Jacob Zeitlin, Ernst Toller und George Antheil