An Inflammation-Centric View of Neurological Disease: Beyond the Neuron

Inflammation is a complex biological response fundamental to how the body deals with injury and infection to eliminate the initial cause of cell injury and effect repair. Unlike a normally beneficial acute inflammatory response, chronic inflammation can lead to tissue damage and ultimately its destruction, and often results from an inappropriate immune response. Inflammation in the nervous system ("neuroinflammation"), especially when prolonged, can be particularly injurious. While inflammation per se may not cause disease, it contributes importantly to disease pathogenesis across both the peripheral (neuropathic pain, fibromyalgia) and central [e.g., Alzheimer disease, Parkinson disease, multiple sclerosis, motor neuron disease, ischemia and traumatic brain injury, depression, and autism spectrum disorder] nervous systems. The existence of extensive lines of communication between the nervous system and immune system represents a fundamental principle underlying neuroinflammation. Immune cell-derived inflammatory molecules are critical for regulation of host responses to inflammation. Although these mediators can originate from various non-neuronal cells, important sources in the above neuropathologies appear to be microglia and mast cells, together with astrocytes and possibly also oligodendrocytes. Understanding neuroinflammation also requires an appreciation that non-neuronal cell-cell interactions, between both glia and mast cells and glia themselves, are an integral part of the inflammation process. Within this context the mast cell occupies a key niche in orchestrating the inflammatory process, from initiation to prolongation. This review will describe the current state of knowledge concerning the biology of neuroinflammation, emphasizing mast cell-glia and glia-glia interactions, then conclude with a consideration of how a cell's endogenousmechanisms might be leveraged to provide a therapeutic strategy to target neuroinflammation

Nanoscale mechanical properties of lipid bilayers and their relevance in biomembrane organization and function

The mechanical properties of biological systems are emerging as fundamental in determining their functional activity. For example, cells continuously probe their environment by applying forces and, at the same time, are exposed to forces produced by the same environment. Also in biological membranes, the activity of membrane related proteins are affected by the overall mechanical properties of the hosting environment. Traditionally, the mesoscopic mechanical properties of lipid bilayers have been studied by micropipette aspiration techniques. In recent years, the possibility of probing mechanical properties of lipid bilayers at the nanoscale has been promoted by the force spectroscopy potentiality of Atomic Force Microscopes (AFM). By acquiring force-curves on supported lipid bilayers (SLBs) it is possible to probe the mechanical properties on a scale relevant to the interaction between membrane proteins and lipid bilayers and to monitor changes of these properties as a result of a changing environment. Here, we review a series of force spectroscopy experiments performed on SLBs with an emphasis on the functional consequences the measured mechanical properties can have on membrane proteins. We also discuss the force spectroscopy experiments on SLBs in the context of theories developed for dynamic force spectroscopy experiments with the aim to extract the kinetic and energetic description of the process of membrane rupture

Choir transhumance in the Filipino Catholic community in Rome

The article is part of a research project (2014-2018) among Christian immigrants in Rome and focuses particularly on the Filipino community. Serena Facci presents the general context of the migrant church experience of Rome, a city historically considered as central to the wider transnational community of Catholic Christians, where, thanks to the hosting politics of the Vicariate, there are several ‘national’ and ‘multinational’ churches, characterised by liturgies in different languages and by repertoires of chants in different geocultural styles. The migrants’ position in the holy city is juxtaposed with the multicentricity of the diaspora and the mediation between the motherland and the new places of residence. Grazia Tuzi shows how the Filipinos in Rome represent this multicentricity through the liturgical services of musical groups and choirs from the peripheral churches surrounding Rome. On Sundays, the Filipino micro-communities proceed in a kind of “transhumant” movement according to a predetermined schedule, from their parishes to the Chaplaincy located in the Basilica of Santa Pudenziana, which is the gathering place of all Filipinos living in Rome. Here they accompany the Sunday liturgy and religious Festivals in performances that bear witness to a remarkable musical variety. The analysis of these musical practices and the complex organization of the choir’s "transhumance" from the periphery to the centre can facilitate the understanding of the processes used by this migrant community in the re-articulation and maintenance of their own identity in the new socio-cultural spheres.  The article is part of a research project (2014-2018) among Christian immigrants in Rome and focuses particularly on the Filipino community. Serena Facci presents the general context of the migrant church experience of Rome, a city historically considered as central to the wider transnational community of Catholic Christians, where, thanks to the hosting politics of the Vicariate, there are several ‘national’ and ‘multinational’ churches, characterised by liturgies in different languages and by repertoires of chants in different geocultural styles. The migrants’ position in the holy city is juxtaposed with the multicentricity of the diaspora and the mediation between the motherland and the new places of residence. Grazia Tuzi shows how the Filipinos in Rome represent this multicentricity through the liturgical services of musical groups and choirs from the peripheral churches surrounding Rome. On Sundays, the Filipino micro-communities proceed in a kind of “transhumant” movement according to a predetermined schedule, from their parishes to the Chaplaincy located in the Basilica of Santa Pudenziana, which is the gathering place of all Filipinos living in Rome. Here they accompany the Sunday liturgy and religious Festivals in performances that bear witness to a remarkable musical variety. The analysis of these musical practices and the complex organization of the choir’s "transhumance" from the periphery to the centre can facilitate the understanding of the processes used by this migrant community in the re-articulation and maintenance of their own identity in the new socio-cultural spheres.

The immunomodulation of porcine immune cells by innate and synthetic host defense peptides

Dendritic cells (DCs) are potent antigen presenting cells (APCs) that link the innate and adaptive immune system by their unique ability to induce and direct immune responses towards various T helper (Th)-type of immune responses such as Th1-, Th2-, Th9-, Th17-, Th22- or T regulatory (TR). The type of Th response generated very much depends on the nature of the antigen encountered and allows for an effective and proficient immune response. For example, Th1 responses are used to clear intracellular pathogens while Th2 responses are needed to clear extracellular pathogens The ability to specifically modulate Th-responses is an area of intense research, as it allows for the development of more effective vaccines and immunotherapeutics. Immunomodulation of DCs is one strategy by which specific Th-type immune responses may be tailored. Current research is focused on identifying agents that have the capacity to immunomodulate DCs such as host defense peptides (HDPs). Apart from their anti-microbial activities, HDPs have a number of immune functions including recruitment and subsequent activation of DCs. The goal of this study was to examine the immunomodulatory effects of HDPs on porcine DC functions. This research was part of a larger multinational research project to develop a novel adjuvant platform for single-immunization vaccines against pertussis in neonates. The pig model was used for this research because of its physiological similarities to humans and the recently developed pertussis infection model in young piglets. A series of experiments was conducted to characterize and describe porcine DC functions. Two subsets of DCs were successfully characterized and tested for their response to stimulation with HDPs. Initial results demonstrated a minimal effect of HDPs on DC functions, therefore we expanded the number of HDPs used to include both synthetic derivatives of HDPs known as innate defense regulators (IDRs) and naturally- occurring HDPs. We examined these effects on peripheral blood mononuclear cells (PBMC) in vitro and found that HDPs induce expression of the chemokine interleukin (IL)-8, which resulted in PBMC recruitment in vitro. We then proceeded to evaluate the HDPs in vivo by intradermally administering them into the flank of pigs. Surprisingly, treatment with the HDPs did not result in recruitment of neutrophils in vivo. We also examined the effects of formulating IDR-1002 as an adjuvant with the academic antigen Keyhole Limpet Hemocyanin (KLH) on the development of KLH-specific immune responses in vaccinated pigs. While there was no difference in antibody titers between vaccinated and control animals, we found that co-formulation with IDR-1002 decreased both antigen-specific and mitogen-induced proliferation in KLH/IDR-1002 vaccinated animals as long as four weeks post-treatment. These results demonstrate that specific IDRs can suppress certain aspects of the pro-inflammatory immune response making them potentially highly versatile tools to modulate and tailor the immune response in disease states characterized by a pro-inflammatory component