Molecular biology of histidine decarboxylase and prostaglandin receptors

Histamine and prostaglandins (PGs) play a variety of physiological roles as autacoids, which function in the vicinity of their sources and maintain local homeostasis in the body. They stimulate target cells by acting on their specific receptors, which are coupled to trimeric G proteins. For the precise understanding of the physiological roles of histamine and PGs, it is necessary to clarify the molecular mechanisms involved in their synthesis as well as their receptor-mediated responses. We cloned the cDNAs for mouse l-histidine decarboxylase (HDC) and 6 mouse prostanoid receptors (4 PGE2 receptors, PGF receptor, and PGI receptor). We then characterized the expression patterns and functions of these genes. Furthermore, we established gene-targeted mouse strains for HDC and PG receptors to explore the novel pathophysiological roles of histamine and PGs. We have here summarized our research, which should contribute to progress in the molecular biology of HDC and PG receptors

Streptococcus uberis strains isolated from the bovine mammary gland evade immune recognition by mammary epithelial cells, but not of macrophages

Streptococcus uberis is frequently isolated from the mammary gland of dairy cattle. Infection with some strains can induce mild subclinical inflammation whilst others induce severe inflammation and clinical mastitis. We compared here the inflammatory response of primary cultures of bovine mammary epithelial cells (pbMEC) towards S. uberis strains collected from clinical or subclinical cases (seven strains each) of mastitis with the strong response elicited by Escherichia coli. Neither heat inactivated nor live S. uberis induced the expression of 10 key immune genes (including TNF, IL1B, IL6). The widely used virulent strain 0140J and the avirulent strain, EF20 elicited similar responses; as did mutants defective in capsule (hasA) or biofilm formation (sub0538 and sub0539). Streptococcus uberis failed to activate NF-κB in pbMEC or TLR2 in HEK293 cells, indicating that S. uberis particles did not induce any TLR-signaling in MEC. However, preparations of lipoteichoic acid (LTA) from two strains strongly induced immune gene expression and activated NF-κB in pbMEC, without the involvement of TLR2. The immune-stimulatory LTA must be arranged in the intact S. uberis such that it is unrecognizable by the relevant pathogen receptors of the MEC. The absence of immune recognition is specific for MEC, since the same S. uberis preparations strongly induced immune gene expression and NF-κB activity in the murine macrophage model cell RAW264.7. Hence, the sluggish immune response of MEC and not of professional immune cells to this pathogen may aid establishment of the often encountered belated and subclinical phenotype of S. uberis mastitis

Real-Time Imaging Reveals the Dynamics of Leukocyte Behaviour during Experimental Cerebral Malaria Pathogenesis

During experimental cerebral malaria (ECM) mice develop a lethal neuropathological syndrome associated with microcirculatory dysfunction and intravascular leukocyte sequestration. The precise spatio-temporal context in which the intravascular immune response unfolds is incompletely understood. We developed a 2-photon intravital microscopy (2P-IVM)-based brain-imaging model to monitor the real-time behaviour of leukocytes directly within the brain vasculature during ECM. Ly6Chi monocytes, but not neutrophils, started to accumulate in the blood vessels of Plasmodium berghei ANKA (PbA)-infected MacGreen mice, in which myeloid cells express GFP, one to two days prior to the onset of the neurological signs (NS). A decrease in the rolling speed of monocytes, a measure of endothelial cell activation, was associated with progressive worsening of clinical symptoms. Adoptive transfer experiments with defined immune cell subsets in recombinase activating gene (RAG)-1-deficient mice showed that these changes were mediated by Plasmodium-specific CD8+ T lymphocytes. A critical number of CD8+ T effectors was required to induce disease and monocyte adherence to the vasculature. Depletion of monocytes at the onset of disease symptoms resulted in decreased lymphocyte accumulation, suggesting reciprocal effects of monocytes and T cells on their recruitment within the brain. Together, our studies define the real-time kinetics of leukocyte behaviour in the central nervous system during ECM, and reveal a significant role for Plasmodium-specific CD8+ T lymphocytes in regulating vascular pathology in this disease. © 2014 Pai et al

Contesting longstanding conceptualisations of urban green space

Ever since the Victorian era saw the creation of “parks for the people,” health and wellbeing benefits have been considered a primary benefit of urban parks and green spaces. Today, public health remains a policy priority, with illnesses and conditions such as diabetes, obesity and depression a mounting concern, notably in increasingly urbanised environments. Urban green space often is portrayed as a nature-based solution for addressing such health concerns. In this chapter, Meredith Whitten investigates how the health and wellbeing benefits these spaces provide are limited by a narrow perspective of urban green space. Whitten explores how our understandings of urban green space remain rooted in Victorian ideals and calls into question how fit for purpose they are in twenty-first-century cities. Calling on empirical evidence collected in three boroughs in London with changing and increasing demographic populations, she challenges the long-held cultural underpinnings that lead to urban green space being portrayed “as a panacea to urban problems, yet treating it as a ‘cosmetic afterthought’” (Whitten, M, Reconceptualising green space: planning for urban green space in the contemporary city. Doctoral thesis, London School of Economics and Political Science, London, U.K. http://etheses.lse.ac.uk/. Accessed 12 Jun 2019, 2019b, p 18)

Blood Interferon Signatures Putatively Link Lack of Protection Conferred by the RTS,S Recombinant Malaria Vaccine to an Antigen-specific IgE Response

Malaria remains a major cause of mortality and morbidity worldwide. Progress has been made in recent years with the development of vaccines that could pave the way towards protection of hundreds of millions of exposed individuals. Here we used a modular repertoire approach to re-analyze a publically available microarray blood transcriptome dataset monitoring the response to malaria vaccination. We report the seminal identification of interferon signatures in the blood of subjects on days 1, 3 and 14 following administration of the third dose of the RTS,S recombinant malaria vaccine. These signatures at day 1 correlate with protection, and at days 3 and 14 to susceptibility to subsequent challenge of study subjects with live parasites. In addition we putatively link the decreased abundance of interferon-inducible transcripts observed at days 3 and 14 post-vaccination with the elicitation of an antigen-specific IgE response in a subset of vaccine recipients that failed to be protected by the RTS,S vaccine. Furthermore, profiling of antigen-specific levels of IgE in a Mozambican cohort of malaria-exposed children vaccinated with RTS,S identified an association between elevated baseline IgE levels and subsequent development of naturally acquired malaria infection during follow up. Taken together these findings warrant further investigation of the role of antigen-specific IgE in conferring susceptibility to malaria infection

BMC Public Health

BACKGROUND: Population health intervention research raises major conceptual and methodological issues. These require us to clarify what an intervention is and how best to address it. This paper aims to clarify the concepts of intervention and context and to propose a way to consider their interactions in evaluation studies, especially by addressing the mechanisms and using the theory-driven evaluation methodology. MAIN TEXT: This article synthesizes the notions of intervention and context. It suggests that we consider an "interventional system", defined as a set of interrelated human and non-human contextual agents within spatial and temporal boundaries generating mechanistic configurations - mechanisms - which are prerequisites for change in health. The evaluation focal point is no longer the interventional ingredients taken separately from the context, but rather mechanisms that punctuate the process of change. It encourages a move towards theorization in evaluation designs, in order to analyze the interventional system more effectively. More particularly, it promotes theory-driven evaluation, either alone or combined with experimental designs. CONCLUSION: Considering the intervention system, hybridizing paradigms in a process of theorization within evaluation designs, including different scientific disciplines, practitioners and intervention beneficiaries, may allow researchers a better understanding of what is being investigated and enable them to design the most appropriate methods and modalities for characterizing the interventional system. Evaluation methodologies should therefore be repositioned in relation to one another with regard to a new definition of "evidence", repositioning practitioners' expertise, qualitative paradigms and experimental questions in order to address the intervention system more profoundly

Joining forces to build up knowledge in health promotion: lessons from a French coalition initiative

International audienceMeeting Abstract IssueFrench public health authorities increasingly rationalize access to public funding, favoring evidence-based programs. Health Promotion (HP) interventions are especially urged to prove their efficiency in this context. To tackle this issue, HP practitioners hold experiential knowledge (EK) that proves useful to assess both the complexity and efficiency of HP interventions. United by this conviction in a multidisciplinary coalition, HP experts from various backgrounds came together five years ago to promote Experiential Knowledge in HP (EKHP) in France.A national committee to promote EKHP670 HP practitioners were surveyed in 2016. Results reported vast amounts of under-documented and often untapped field expertise in HP and numerous obstacles regarding access to scientific literature or systematic reviews. Consequently, the coalition launched a National Committee for EKHP, meeting 5 times a year since 2016. Members of 6 national HP organizations, of 4 regional HP institutes, national and local public health administrators, researchers, consultants and field workers participate. Steered by the French Society for Public Health and the National Federation for Health Education and Promotion, the committee devised a threefold action plan: 1/ advocate EKHP in all relevant institutional spaces, 2/ develop tools for EKHP, 3/ mobilize for EKHP at the local level.ResultsThe committee designed a method for capitalizing, collecting and circulating EK and published in 2020 a guidebook and a toolkit. French Public Health authorities agreed to share EK nationwide on their online portal. Dissemination within the French HP community has started, through the committee members' networks, and will be amplified with a training program launched in 2021 at the National School of Public Health.LessonsAttention must be brought to HP practitioners’ experiential knowledge, both to recognize HP practitioners' expertise and to help improve the understanding of how HP interventions work.Key messages Experiential knowledge in HP remains undervalued and untapped in France. Dedicated practitioners, policymakers and researchers formed a multidisciplinary committee to promote and disseminate EKHP. A multilevel strategy combining advocacy and tool building can be effective at promoting experiential knowledge. A multidisciplinary coalition provided the necessary context-specific levers in France

Who, why, when and how do people use urban green spaces? A study of users from 18 parks in France

Urban green spaces impact the individual and collective health of populations. At the city level, they act as regulators of environmental hazards and constitute collective protective factors. At the individual level, they constitute social spaces for encounters and rejuvenation. But, these functions depend on the use made of these green spaces which can be inequitable. This paper presents the results of the analysis of the use of green spaces in the 6 French cities selected in the WHO French Healthy City Network conducted as part of the GREENH-City research project