Leave no city behind

Close to 4 billion people live in cities. As the driver of environmental challenges, accounting for nearly 70% of the world's carbon emissions, and as sites of critical social disparities, with 863 million dwellers now living in slums, urban settlements are at the heart of global change. This momentum is unlikely to disappear, as approximately 70 million more people will move to cities by the end of this year alone. The good news is that recent multilateral processes are now appreciating this key role of cities and are increasingly prioritizing urban concerns in policy-making. Yet, how can we ensure that these steps toward a global urban governance leave no city, town, or urban dweller behind

Science and the Future of Cities: Interim Report of the Nature Sustainability Expert Panel

This short interim report introduces the work of the Nature Sustainability Expert Panel on science and the future of cities. Developed in partnership by University College London’s City Leadership Lab and Nature Sustainability, and supported by UCL’s Grand Challenge of Sustainable Cities, the expert panel focuses on the urban science-policy interface for global sustainability. It offers a first look into the themes that will be developed in the upcoming Panel’s report (July 2018). The document here discusses existing tensions in the current global urban science landscape and explores how those could be overcome to make existing urban research more responsive to global urban sustainability challenges

Mobilising urban knowledge in an infodemic: Urban observatories, sustainable development and the COVID-19 crisis

Along with disastrous health and economic implications, COVID-19 has also been an epidemic of misinformation and rumours – an ‘infodemic’. The desire for robust, evidence-based policymaking in this time of disruption has been at the heart of the multilateral response to the crisis, not least in terms of supporting a continuing agenda for global sustainable development. The role of boundary-spanning knowledge institutions in this context could be pivotal, not least in cities, where much of the pandemic has struck. ‘Urban observatories’ have emerged as an example of such institutions; harbouring great potential to produce and share knowledge supporting sustainable and equitable processes of recovery. Building on four ‘live’ case studies during the crisis of institutions based in Johannesburg, Karachi, Freetown and Bangalore, our research note aims to capture the role of these institutions, and what it means to span knowledge boundaries in the current crisis. We do so with an eye towards a better understanding of their knowledge mobilisation practices in contributing towards sustainable urban development. We highlight that the crisis offers a key window for urban observatories to play a progressive and effective role for sustainable and inclusive development. However, we also underline continuing challenges in these boundary knowledge dynamics: including issues of institutional trust, inequality of voices, collective memory, and the balance between normative and advisory roles for observatories

CD28 costimulatory signal induces protein arginine methylation in T cells

Protein phosphorylation initiates signal transduction that triggers lymphocyte activation. However, other posttranslational modifications may contribute to this process. Here, we show that CD28 engagement induced protein arginine methyltransferase activity and methylation on arginine of several proteins, including Vav1. Methylation of Vav1 and IL-2 production were reduced by inhibiting S-adenosyl-L-homocysteine hydrolase, an enzyme that regulates cellular transmethylation. Methylated Vav1 was induced in human and mouse T cells and selectively localized in the nucleus, which suggested that this form marks a nuclear function of Vav1. Our findings uncover a signaling pathway that is controlled by CD28 that is likely to be important for T cell activation

Functional characterization of the sea urchin sns chromatin insulator in erythroid cells

Chromatin insulators are regulatory elements that determine domains of genetic functions. We have previously described the characterization of a 265 bp insulator element, termed sns, localized at the 3' end of the early historic H2A gene of the sea urchin Paracentrotus lividus. This sequence contains three cis-acting elements (Box A, Box B, and Box C+T) all needed for the enhancer-blocking activity in both sea urchin and human cells. The goal of this Study was to further characterize the sea urchin sns insulator in the erythroid environment. We employed colony assays in human (K562) and mouse (MEL) erythroid cell lines. We tested the capability of sns to interfere with the communication between the 5HS2 enhancer of the human beta-globin LCR and the gamma-globin promoter. We found that the sns sequence displays directional enhancer-blocking activity. By the use of antibodies against known DNA binding proteins, in electrophoretic mobility shift assays, we demonstrated the binding of the erythroid-specific GATA-1 and the ubiquitous Oct-1 and Sp1 transcription factors. These factors bind to Box A, Box B, and Box C+T, respectively, in both K562 and MEL nuclear extracts. These results may have significant implications for the conservation of insulator function ill evolutionary distant organisms and may prove to be of practical benefit in gene transfer applications for erythroid disorders such as hemoglobinopathies and thalassemias

A model independent and rephase invariant parametrization of CP violation

The phenomenological description of the neutral B meson system is proposed in terms of the fundamental CP-violating observables and within a rephasing invariant formalism. This generic formalism can select the time-dependent and time-integrated asymmetries which provide the basic tools to discriminate the different kinds of possible CP-violating effects in dedicated experimental B-meson facilities.Comment: 19 pages, Plain Te

Proximal changes in signal transduction that modify CD8+ T cell responsiveness in vivo

The antigen dose conditions the functional properties of CD8+ T cells generated after priming. At relatively low antigen doses, efficient memory T cells may be generated, while high antigen doses lead to tolerance. To determine the mechanisms leading to such different functional outcomes, we compared the proximal TCR signal transduction of naive cells, to that of memory or high-dose tolerant cells generated in vivo. In vivo activation led to the constitutive phosphorylation of CD3 4 , recruiting Zap70, in both memory and tolerant cells. In tolerant cells, these phenomena were much more marked, the CD3 4 and ´ chains no longer associated, and the Src kinases p56Lck and p59Fyn were inactive. Therefore, when the antigen load overcomes the capacities of immune control, a new mechanism intervenes to block signal transduction: the recruitment of Zap70 to CD3 4 becomes excessive, leading to TCR complex destabilization, Src kinase dysfunction, and signal arrest

An optimized procedure for preparation of conditioned medium from Wharton’s jelly mesenchymal stromal cells isolated from umbilical cord

Cell-free therapy based on conditioned medium derived from mesenchymal stromal cells (MSCs) has gained attention in the field of protective and regenerative medicine. However, the exact composition and properties of MSC-derived conditioned media can vary greatly depending on multiple parameters, which hamper standardization. In this study, we have optimized a procedure for preparation of conditioned medium starting from efficient isolation, propagation and characterization of MSCs from human umbilical cord, using a culture medium supplemented with human platelet lysate as an alternative source to fetal bovine serum. Our procedure successfully maximizes the yield of viable MSCs that maintain canonical key features. Importantly, under these conditions, the compositional profile and biological effects elicited by the conditioned medium preparations derived from these MSC populations do not depend on donor individuality. Moreover, approximately 120 L of conditioned medium could be obtained from a single umbilical cord, which provides a suitable framework to produce industrial amounts of toxic-free conditioned medium with predictable composition

Wharton’s Jelly Mesenchymal Stromal Cells Support the Expansion of Cord Blood–derived CD34 + Cells Mimicking a Hematopoietic Niche in a Direct Cell–cell Contact Culture System

Wharton’s jelly mesenchymal stromal cells (WJ-MSCs) have been recently exploited as a feeder layer in coculture systems to expand umbilical cord blood–hematopoietic stem/progenitor cells (UCB-HSPCs). Here, we investigated the role of WJ-MSCs in supporting ex vivo UCB-HSPC expansion either when cultured in direct contact (DC) with WJ-MSCs or separated by a transwell system or in the presence of WJ-MSC–conditioned medium. We found, in short-term culture, a greater degree of expansion of UCB-CD34 + cells in a DC system (15.7 ± 4.1-fold increase) with respect to the other conditions. Moreover, in DC, we evidenced two different CD34 + cell populations (one floating and one adherent to WJ-MSCs) with different phenotypic and functional characteristics. Both multipotent CD34 + /CD38 − and lineage-committed CD34 + /CD38 + hematopoietic progenitors were expanded in a DC system. The former were significantly more represented in the adherent cell fraction than in the floating one (18.7 ± 11.2% vs. 9.7 ± 7.9% over the total CD34 + cells). Short-term colony forming unit (CFU) assays showed that HSPCs adherent to the stromal layer were able to generate a higher frequency of immature colonies (CFU-granulocyte/macrophage and burst-forming unit erythroid/large colonies) with respect to the floating cells. In the attempt to identify molecules that may play a role in supporting the observed ex vivo HSPC growth, we performed secretome analyses. We found a number of proteins involved in the HSPC homing, self-renewal, and differentiation in all tested conditions. It is important to note that a set of sixteen proteins, which are only in part reported to be expressed in any hematopoietic niche, were exclusively found in the DC system secretome. In conclusion, WJ-MSCs allowed a significant ex vivo expansion of multipotent as well as committed HSPCs. This may be relevant for future clinical applications

Exorcising Malthusian ghosts: Vaccinating the Nexus to advance integrated water, energy and food resource resilience

Water-Energy-Food (WEF) Nexus interactions vary from seemingly negative and intractable wicked problems to opportunities for enhanced sustainability. The aim of this paper is to review the current state of understanding on WEF resource interactions and to provide a roadmap to enhance integrated resource management. A qualitative perspective based on expert insight and experience was supported by a more quantitative systematic analysis of the literature to define Nexus interactions, describe the nature of different challenges, and explore the factors that influence them. We found that Nexus challenges, and associated interactions (e.g. trade-offs and synergies), vary with complexity and spatial and temporal scale, and biases in research and culture act as barriers to progress. An interdisciplinary approach is needed to develop technical solutions employed through the use of orchestrated shocks (e.g. historic analogues, predictive modelling, experimentation, and scenario planning) to “Vaccinate the Nexus” and improve system resilience. To achieve this, multidisciplinary capability should be developed to solve interdisciplinary challenges, while protecting specialism. It is recognised that through embracing complexity and “Nexus (or Systems) Thinking”, future integration of resource management may be facilitated through holistic education, informed by interdisciplinary research, and ingrained in cross-sector policy and governance