How do cities approach policy innovation and policy learning? A study of 30 policies in Northern Europe and North America

This paper reports on a study of current practice in policy transfer, and ways in which its effectiveness can be increased. A literature review identifies important factors in examining the transfer of policies. Results of interviews in eleven cities in Northern Europe and North America investigate these factors further. The principal motivations for policy transfer were strategic need and curiosity. Local officials and politicians dominated the process of initiating policy transfer, and local officials were also the leading players in transferring experience. A range of information sources are used in the search process but human interaction was the most important source of learning for two main reasons. First, there is too much information available through the Internet and the search techniques are not seen to be wholly effective in identifying the necessary information. Secondly, the information available on websites, portals and even good practice guides is not seen to be of mixed quality with risks of focussing only on successful implementation and therefore subject to some bias. Officials therefore rely on their trusted networks of peers for lessons as here they can access the ‘real implementation’ story and the unwritten lessons. Organisations which have a culture that is supportive of learning from elsewhere had strong and broad networks of external contacts and resourced their development whilst others are more insular or inward looking and reluctant to invest in policy lessons from elsewhere. Solutions to the problems identified in the evidence base are proposed

Genetically engineered minipigs model the major clinical features of human neurofibromatosis type 1.

Neurofibromatosis Type 1 (NF1) is a genetic disease caused by mutations in Neurofibromin 1 (NF1). NF1 patients present with a variety of clinical manifestations and are predisposed to cancer development. Many NF1 animal models have been developed, yet none display the spectrum of disease seen in patients and the translational impact of these models has been limited. We describe a minipig model that exhibits clinical hallmarks of NF1, including café au lait macules, neurofibromas, and optic pathway glioma. Spontaneous loss of heterozygosity is observed in this model, a phenomenon also described in NF1 patients. Oral administration of a mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor suppresses Ras signaling. To our knowledge, this model provides an unprecedented opportunity to study the complex biology and natural history of NF1 and could prove indispensable for development of imaging methods, biomarkers, and evaluation of safety and efficacy of NF1-targeted therapies

Laminin-332 alters connexin profile, dye coupling and intercellular Ca(2+ )waves in ciliated tracheal epithelial cells

BACKGROUND: Tracheal epithelial cells are anchored to a dynamic basement membrane that contains a variety of extracellular matrix proteins including collagens and laminins. During development, wound repair and disease of the airway epithelium, significant changes in extracellular matrix proteins may directly affect cell migration, differentiation and events mediated by intercellular communication. We hypothesized that alterations in cell matrix, specifically type I collagen and laminin α3β3γ2 (LM-332) proteins within the matrix, directly affect intercellular communication in ciliated rabbit tracheal epithelial cells (RTEC). METHODS: Functional coupling of RTEC was monitored by microinjection of the negatively charged fluorescent dyes, Lucifer Yellow and Alexa 350, into ciliated RTEC grown on either a LM-332/collagen or collagen matrix. Coupling of physiologically significant molecules was evaluated by the mechanism and extent of propagated intercellular Ca(2+ )waves. Expression of connexin (Cx) mRNA and proteins were assayed by reverse transcriptase – polymerase chain reaction and immunocytochemistry, respectively. RESULTS: When compared to RTEC grown on collagen alone, RTEC grown on LM-332/collagen displayed a significant increase in dye transfer. Although mechanical stimulation of RTEC grown on either LM-332/collagen or collagen alone resulted in intercellular Ca(2+ )waves, the mechanism of transfer was dependent on matrix: RTEC grown on LM-332/collagen propagated Ca(2+)waves via extracellular purinergic signaling whereas RTEC grown on collagen used gap junctions. Comparison of RTEC grown on collagen or LM-332/collagen matrices revealed a reorganization of Cx26, Cx43 and Cx46 proteins. CONCLUSION: Alterations in airway basement membrane proteins such as LM-332 can induce connexin reorganizations and result in altered cellular communication mechanisms that could contribute to airway tissue function

Consideration of pannexin 1 channels in covid-19 pathology and treatment

Copyright © 2020 the American Physiological Society Pannexin 1 (PANX1) is a ubiquitously expressed, channel-forming protein found in a number of tissues throughout the body (e.g., lung, vasculature, liver, central nervous system, immune system) that is important in many key physiological and immune responses (18, 55). PANX1 channels passively flux ATP (predominantly), multiple metabolites, and likely other small anions (37, 39). PANX1 channels regulate inflammation and host responses to several pathogens, including viruses (36, 42, 53). While there is currently no evidence suggesting novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and PANX1 directly interact, there is an urgent need for therapeutic strategies, especially those targeting the hyperinflammation and cytokine storm that occurs in severe cases of COVID-19 (27, 41). Here we argue that PANX1, and drugs known to target PANX1 (including the FDA-approved drug probenecid), should be the focus of further investigation in the context of SARS-CoV-2 infection and its associated pathology in COVID-19 patients

Keeping secrets from parents: Longitudinal associations of secrecy in adolescence

Contains fulltext : 55705.pdf (publisher's version ) (Closed access)A 2-wave survey study among 1173 10-14-year-olds tested the longitudinal contribution of secrecy from parents to psychosocial and behavioral problems in adolescence. Additionally, it investigated a hypothesized contribution of secrecy from parents to adolescent development by examining its relation with self-control. Results showed that keeping secrets from parents is associated with substantial psychosocial and behavioral disadvantages in adolescence even after controlling for possible confounding variables, including communication with parents, trust in parents, and perceived parental supportiveness. Contrary to prediction, secrecy was also negatively associated with feelings of self-control. Secrecy from parents thus appears to be an important risk factor for adolescent psychosocial well-being and behavioral adjustment.12 p

Immunodominant T Cell Determinants of Aquaporin-4, the Autoantigen Associated with Neuromyelitis Optica

Autoantibodies that target the water channel aquaporin-4 (AQP4) in neuromyelitis optica (NMO) are IgG1, a T cell-dependent Ig subclass. However, a role for AQP4-specific T cells in this CNS inflammatory disease is not known. To evaluate their potential role in CNS autoimmunity, we have identified and characterized T cells that respond to AQP4 in C57BL/6 and SJL/J mice, two strains that are commonly studied in models of CNS inflammatory diseases. Mice were immunized with either overlapping peptides or intact hAQP4 protein encompassing the entire 323 amino acid sequence. T cell determinants identified from examination of the AQP4 peptide (p) library were located within AQP4 p21-40, p91-110, p101-120, p166-180, p231-250 and p261-280 in C57BL/6 mice, and within p11-30, p21-40, p101-120, p126-140 and p261-280 in SJL/J mice. AQP4-specific T cells were CD4+ and MHC II-restricted. In recall responses to immunization with intact AQP4, T cells responded primarily to p21-40, indicating this region contains the immunodominant T cell epitope(s) for both strains. AQP4 p21-40-primed T cells secreted both IFN-γ and IL-17. The core immunodominant AQP4 21-40 T cell determinant was mapped to residues 24-35 in C57BL/6 mice and 23-35 in SJL/J mice. Our identification of the AQP4 T cell determinants and characterization of its immunodominant determinant should permit investigators to evaluate the role of AQP4-specific T cells in vivo and to develop AQP4-targeted murine NMO models

Assessing External Effects of City Airports: Land Values in Berlin

This paper employs a hedonic price model to explain standard land values in Berlin. Impact on land values is assessed for the two city airports situated in Berlin, Germany, Tempelhof and Tegel. Empirical results confirm expectations about the impact of various attributes on land values. Areas exposed to noise pollution of downtown airport Tempelhof sell at a discount of approximately 5-9% within a distance of 5000 m along the air corridor. No significantly negative impact was found for land values around Tegel Airport, which is located in a central, but less densely populated, area. Market access indicators created for all three Berlin airports in operation, including Berlin Schoenefeld International Airport, reveal clear location advantages in terms of accessibility of Tempelhof and Tegel compared to Schoenefeld Airport, where the new Berlin Brandenburg International Airport is about to be developed

Role of the Gut Endoderm in Relaying Left-Right Patterning in Mice

Analysis of Sox17 mutant mice reveals that gap junction coupling across the gut endoderm of the embryo transmits the left-right asymmetric signal from the node to the site of asymmetric organogenesis in mice