Monitoring brain activity with protein voltage and calcium sensors

© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 5 (2015): 10212, doi:10.1038/srep10212.Understanding the roles of different cell types in the behaviors generated by neural circuits requires protein indicators that report neural activity with high spatio-temporal resolution. Genetically encoded fluorescent protein (FP) voltage sensors, which optically report the electrical activity in distinct cell populations, are, in principle, ideal candidates. Here we demonstrate that the FP voltage sensor ArcLight reports odor-evoked electrical activity in the in vivo mammalian olfactory bulb in single trials using both wide-field and 2-photon imaging. ArcLight resolved fast odorant-responses in individual glomeruli, and distributed odorant responses across a population of glomeruli. Comparisons between ArcLight and the protein calcium sensors GCaMP3 and GCaMP6f revealed that ArcLight had faster temporal kinetics that more clearly distinguished activity elicited by individual odorant inspirations. In contrast, the signals from both GCaMPs were a saturating integral of activity that returned relatively slowly to the baseline. ArcLight enables optical electrophysiology of mammalian neuronal population activity in vivo.Supported by US NIH DC005259, WCI 2009-003 from the National Research Foundation of Korea, a James Hudson Brown – Alexander Brown Coxe fellowship from Yale University, and a Ruth L. Kirschstein National Research Service Award DC012981

In Search of a Common European Approach to a Healthy Indoor Environment

Increasingly, policymakers in Europe and around the world are realizing the importance of healthy indoor environments for public health. Certain member states of the European Union (EU) have already achieved successes in improving indoor environmental quality, such as controlling certain contaminants (e.g., environmental tobacco smoke) or developing nationwide policies that address indoor air generally. However, a common European approach to achieving healthy indoor environments is desirable for several reasons including providing a broader recognition of the problem of unhealthy indoor air, setting a policy example for all 27 EU member states, and achieving greater public health equity across the different European nations. In this article we address the question “Why is it so difficult in the EU to develop a coherent approach on indoor environment?” We identify and describe four main barriers: a) the subsidiarity principle in EU policymaking, introducing decentralization of decision making to the member states; b) fragmentation of the topic of the indoor environment; c) the differences in climate and governance among different member states that make a common policy difficult; and d) economic issues. We discuss potential lessons and recommendations from EU and U.S. successes in achieving healthier indoor environments through various policy mechanisms

Environmental, health, wellbeing, social and equity effects of urban green space interventions: A meta-narrative evidence synthesis

© 2019 The Authors Background: As populations become increasingly urbanised, the preservation of urban green space (UGS) becomes paramount. UGS is not just dedicated recreational space such as public parks, but other types of informal green space are important, for example, street trees and roof gardens. Despite the potential from cross-sectional evidence, we know little about how to design new, or improve or promote existing UGS for health, wellbeing, social and environmental benefits, or known influencing factors such as physical activity. Objectives: To perform a meta-narrative review of the evidence regarding the health, wellbeing, social, environmental and equity effects, or known influencing factors of these outcomes, of UGS interventions. Data sources: Eight electronic databases were searched ((Medline, PsycINFO, Web of Science (Science and Social Science Citation Indices), PADDI (Planning Architecture Design Database Ireland), Zetoc, Scopus, Greenfiles, SIGLE (System for Information on Grey Literature in Europe)), and reference lists of included studies and relevant reviews were hand searched for further relevant studies. Study eligibility criteria, participants, and interventions: Eligibility criteria included: (i) evaluation of an UGS intervention; and (ii) health, wellbeing, social or environmental outcome(s), or known influencing factors of these outcomes, measured. Interventions involving any age group were included. Interventions must have involved: (a) physical change to green space in an urban-context including improvements to existing UGS or development of new UGS, or (b) combination of physical change to UGS supplemented by a specific UGS awareness, marketing or promotion programme to encourage use of UGS. Study appraisal and synthesis methods: Following a meta-narrative approach, evidence was synthesised by main intervention approach, including: (i) park-based; (ii) greenways/trails; (iii) urban greening; (iv) large green built projects for environmental purposes. Outcomes such as economic (e.g. cost effectiveness and cost–benefit analyses), adverse effects and unintended consequences were also extracted. Evidence was synthesised following the RAMESES guidelines and publication standards, the PROGRESS-plus tool was used to explore equity impact, and risk of bias/study quality was assessed. The findings from the evidence review were presented at an expert panel representing various disciplines in a workshop and these discussions framed the findings of the review and provide recommendations that are relevant to policy, practice and research. Results: Of the 6997 studies identified, 38 were included. There was strong evidence to support park-based (7/7 studies) and greenway/trail (3/3 studies) interventions employing a dual-approach (i.e. a physical change to the UGS and promotion/marketing programmes) particularly for park use and physical activity; strong evidence for the greening of vacant lots (4/4 studies) for health, wellbeing (e.g. reduction in stress) and social (e.g. reduction in crime, increased perceptions of safety) outcomes; strong evidence for the provision of urban street trees (3/4 studies) and green built interventions for storm water management (6/7 studies) for environmental outcomes (e.g. increased biodiversity, reduction in illegal dumping). Park-based or greenway/trail interventions that did not employ a dual-approach were largely ineffective (7/12 studies showed no significant intervention effect). Overall, the included studies have inherent biases owing to the largely non-randomized study designs employed. There was too little evidence to draw firm conclusions regarding the impact of UGS interventions on a range of equity indicators. Limitations; conclusions and implications of key findings: UGS has an important role to play in creating a culture of health and wellbeing. Results from this study provide supportive evidence regarding the use of certain UGS interventions for health, social and environmental benefits. These findings should be interpreted in light of the heterogeneous nature of the evidence base, including diverging methods, target populations, settings and outcomes. We could draw little conclusions regarding the equity impact of UGS interventions. However, the true potential of UGS has not been realised as studies have typically under-evaluated UGS interventions by not taking account of the multifunctional nature of UGS. The findings have implications for policymakers, practitioners and researchers. For example, for policymakers the trajectory of evidence is generally towards a positive association between UGS and health, wellbeing, social and environmental outcomes, but any intervention must ensure that negative consequences of gentrification and unequal access are minimised

Separating Agent-Functioning and Inter-Agent Coordination by Activated Modules: The DECOMAS Architecture

The embedding of self-organizing inter-agent processes in distributed software applications enables the decentralized coordination system elements, solely based on concerted, localized interactions. The separation and encapsulation of the activities that are conceptually related to the coordination, is a crucial concern for systematic development practices in order to prepare the reuse and systematic integration of coordination processes in software systems. Here, we discuss a programming model that is based on the externalization of processes prescriptions and their embedding in Multi-Agent Systems (MAS). One fundamental design concern for a corresponding execution middleware is the minimal-invasive augmentation of the activities that affect coordination. This design challenge is approached by the activation of agent modules. Modules are converted to software elements that reason about and modify their host agent. We discuss and formalize this extension within the context of a generic coordination architecture and exemplify the proposed programming model with the decentralized management of (web) service infrastructures

CAMP-BDI: A Pre-emptive Approach for Plan Execution Robustness in Multiagent Systems

Abstract. Belief-Desire-Intention agents in realistic environments may face un-predictable exogenous changes threatening intended plans and debilitative failure effects that threaten reactive recovery. In this paper we present the CAMP-BDI (Capability Aware, Maintaining Plans) approach, where BDI agents utilize intro-spective reasoning to modify intended plans in avoidance of anticipated failure. We also describe an extension of this approach to the distributed case, using a de-centralized process driven by structured messaging. Our results show significant improvements in goal achievement over a reactive failure recovery mechanism in a stochastic environment with debilitative failure effects, and suggest CAMP-BDI offers a valuable complementary approach towards agent robustness.

The APEX framework: prototyping of ubiquitous environments based on Petri Nets

The user experience of ubiquitous environments is a determining factor in their success. The characteristics of such systems must be explored as early as possible to anticipate potential user problems, and to reduce the cost of redesign. However, the development of early prototypes to be evaluated in the target environment can be disruptive to the ongoing system and therefore unacceptable. This paper reports on an ongoing effort to explore how model-based rapid prototyping of ubiquitous environments might be used to avoid actual deployment while still enabling users to interact with a representation of the system. The paper describes APEX, a framework that brings together an existing 3D Application Server with CPN Tools. APEX-based prototypes enable users to navigate a virtual world simulation of the envisaged ubiquitous environment. The APEX architecture and the proposed CPN-based modelling approach are described. An example illustrates their use.Fundação para a Ciência e a Tecnologia (FCT) - bolsa de doutoramento SFRH/BD/41179/200

Congenital deficiency reveals critical role of ISG15 in skin homeostasis

Ulcerating skin lesions are manifestations of human ISG15 deficiency, a type I interferonopathy. However, chronic inflammation may not be their exclusive cause. We describe two siblings with recurrent skin ulcers that healed with scar formation upon corticosteroid treatment. Both had a homozygous nonsense mutation in the ISG15 gene, leading to unstable ISG15 protein lacking the functional domain. We characterized ISG15(-/-) dermal fibroblasts, HaCaT keratinocytes, and human induced pluripotent stem cell-derived vascular endothelial cells. ISG15-deficient cells exhibited the expected hyperinflammatory phenotype, but also dysregulated expression of molecules critical for connective tissue and epidermis integrity, including reduced collagens and adhesion molecules, but increased matrix metalloproteinases. ISG15(-/-) fibroblasts exhibited elevated ROS levels and reduced ROS scavenger expression. As opposed to hyperinflammation, defective collagen and integrin synthesis was not rescued by conjugation-deficient ISG15. Cell migration was retarded in ISG15(-/-) fibroblasts and HaCaT keratinocytes, but normalized under ruxolitinib treatment. Desmosome density was reduced in an ISG15(-/-) 3D epidermis model. Additionally, there were loose architecture and reduced collagen and desmoglein expression, which could be reversed by treatment with ruxolitinib/doxycycline/TGF-beta 1. These results reveal critical roles of ISG15 in maintaining cell migration and epidermis and connective tissue homeostasis, whereby the latter likely requires its conjugation to yet unidentified targets

Development of a quantitative methodology to assess the impacts of urban transport interventions and related noise on well-being

Well-being impact assessments of urban interventions are a difficult challenge, as there is no agreed methodology and scarce evidence on the relationship between environmental conditions and well-being. The European Union (EU) project "Urban Reduction of Greenhouse Gas Emissions in China and Europe" (URGENCHE) explored a methodological approach to assess traffic noise-related well-being impacts of transport interventions in three European cities (Basel, Rotterdam and Thessaloniki) linking modeled traffic noise reduction effects with survey data indicating noise-well-being associations. Local noise models showed a reduction of high traffic noise levels in all cities as a result of different urban interventions. Survey data indicated that perception of high noise levels was associated with lower probability of well-being. Connecting the local noise exposure profiles with the noise-well-being associations suggests that the urban transport interventions may have a marginal but positive effect on population well-being. This paper also provides insight into the methodological challenges of well-being assessments and highlights the range of limitations arising from the current lack of reliable evidence on environmental conditions and well-being. Due to these limitations, the results should be interpreted with caution

Architecting the IoT Paradigm: A Middleware for Autonomous Distributed Sensor Networks

Actualizing Internet of Things undoubtedly constitutes a major challenge of modern computing and is a promising next step in realizing the unification of all seamlessly interacting entities, either human users or participating machines, under a shared, coherent architecture. While it has now become common belief that the related solutions should be based on compatible network infrastructure employing widely accepted communication schemes, the specifics of the intermediate system that would act as global interface for all involved “things” are yet to be determined. A rising trend to define such machine-based entities is through cyber-physical systems, in terms of collaborating elements with physical input and output. Certainly, sensor networks constitute the most representative realization of such systems. Taking these issues and opportunities under consideration, this work proposes a bioinspired distributed architecture for an Internet of Things that exhibits self-organization properties to enable efficient interaction between entities modeled as cyber-physical systems, mainly focusing on sensor networks. Furthermore, a middleware has been implemented according to the proposed architecture, which serves the role of the backbone of this network as a multiagent and autonomous distributed system. The evaluation results demonstrate the self-optimization properties of the introduced scheme and indicate global network convergence

Schistosome Eggs Impair Protective Th1/Th17 Immune Responses Against Salmonella Infection

Countries with a high incidence of helminth infections are characterized by high morbidity and mortality to infections with intracellular pathogens such as Salmonella. Some patients with Salmonella-Schistosoma co-infections develop a so-called “chronic septicemic salmonellosis,” with prolonged fever and enlargement of the liver and spleen. These effects are most likely due to the overall immunoregulatory activities of schistosomes such as induction of Tregs, Bregs, alternatively activated macrophages, and degradation of antibodies. However, detailed underlying mechanisms are not very well investigated. Here, we show that intraperitoneal application of live Schistosoma mansoni eggs prior to infection with Salmonella Typhimurium in mice leads to an impairment of IFN-γ and IL-17 responses together with a higher bacterial load compared to Salmonella infection alone. S. mansoni eggs were found in granulomas in the visceral peritoneum attached to the colon. Immunohistological staining revealed IPSE/alpha-1, a glycoprotein secreted from live schistosome eggs, and recruited basophils around the eggs. Noteworthy, IPSE/alpha-1 is known to trigger IL-4 and IL-13 release from basophils which in turn is known to suppress Th1/Th17 responses. Therefore, our data support a mechanism of how schistosomes impair a protective immune response against Salmonella infection and increase our understanding of helminth-bacterial co-infections