Antigen Drives Regulatory B10 Cell Development and Function

B cells mediate immune responses via the secretion of antibody and interactions with other immune cell populations through antigen presentation, costimulation, and cytokine secretion. Although B cells are primarily believed to promote immune responses using the mechanisms described above, some unique regulatory B cell populations that negatively influence inflammation have also been described. Among these is a rare interleukin (IL)-10-producing B lymphocyte subset termed “B10 cells.” B cell-derived IL-10 can inhibit various arms of the immune system, including polarization of Th1/Th2 cell subsets, antigen presentation and cytokine production by monocytes and macrophages, and activation of regulatory T cells. Further studies in numerous autoimmune and inflammatory models of disease have confirmed the ability of B10 cells to negatively regulate inflammation in an IL-10-dependent manner. Although IL-10 is indispensable to the effector functions of B10 cells, how this specialized B cell population is selected in vivo to produce IL-10 is unknown. Some studies have demonstrated a link between B cell receptor (BCR)-derived signals and the acquisition of IL-10 competence. Additionally, whether antigen-BCR interactions are required for B cell IL-10 production during homeostasis as well as active immune responses is a matter of debate. Therefore, the goal of this thesis is to determine the importance of antigen-driven signals during B10 cell development in vivo and during B10 cell-mediated immunosuppression.

Chapter 3 of the dissertation explored the BCR repertoire of spleen and peritoneal cavity B10 cells using single-cell sequencing to lay the foundation for studies to understand the full range of antigens that may be involved in B10 cell selection. In both the spleen and peritoneal cavity B10 cells studied, BCR gene utilization was diverse, and the expressed BCR transcripts were largely unmutated. Thus, B10 cells are likely capable of responding to a wide range of foreign and self-antigens in vivo.

Studies in Chapter 4 determined the predominant antigens that drive B cell IL-10 secretion during homeostasis. A novel in vitro B cell expansion system was used to isolate B cells actively expressing IL-10 in vivo and probe the reactivities of their secreted monoclonal antibodies. B10 cells were found to produce polyreactive antibodies that bound multiple self-antigens. Therefore, in the absence of overarching active immune responses, B cell IL-10 is secreted following interactions with self-antigens.

Chapter 5 of this dissertation investigated whether foreign antigens are capable of driving B10 cell expansion and effector activity during an active immune response. In a model of contact-induced hypersensitivity, in vitro B cell expansion was again used to isolate antigen-specific B10 clones, which were required for optimal immunosuppression.

The studies described in this dissertation shed light on the relative contributions of BCR-derived signals during B10 cell development and effector function. Furthermore, these investigations demonstrate that B10 cells respond to both foreign and self-antigens, which has important implications for the potential manipulation of B10 cells for human therapy. Therefore, B10 cells represent a polyreactive B cell population that provides antigen-specific regulation of immune responses via the production of IL-10.

Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage.

Diarthrodial joints are essential for load bearing and locomotion. Physiologically, articular cartilage sustains millions of cycles of mechanical loading. Chondrocytes, the cells in cartilage, regulate their metabolic activities in response to mechanical loading. Pathological mechanical stress can lead to maladaptive cellular responses and subsequent cartilage degeneration. We sought to deconstruct chondrocyte mechanotransduction by identifying mechanosensitive ion channels functioning at injurious levels of strain. We detected robust expression of the recently identified mechanosensitive channels, PIEZO1 and PIEZO2. Combined directed expression of Piezo1 and -2 sustained potentiated mechanically induced Ca(2+) signals and electrical currents compared with single-Piezo expression. In primary articular chondrocytes, mechanically evoked Ca(2+) transients produced by atomic force microscopy were inhibited by GsMTx4, a PIEZO-blocking peptide, and by Piezo1- or Piezo2-specific siRNA. We complemented the cellular approach with an explant-cartilage injury model. GsMTx4 reduced chondrocyte death after mechanical injury, suggesting a possible therapy for reducing cartilage injury and posttraumatic osteoarthritis by attenuating Piezo-mediated cartilage mechanotransduction of injurious strains.

Wounds that heal and wounds that don't - The role of the IL-33/ST2 pathway in tissue repair and tumorigenesis

IL-33 is a member of the IL-1 family of cytokines. IL-33 is predominantly located within the nucleus of cells where it plays a role in gene regulation. Given the right combination of signals and cellular damage, stored IL-33 is released from the cell where it can interact with its receptor ST2, triggering danger-associated responses and act as a cellular "alarmin". Whilst IL-33/ST2 signalling has been shown to induce potent pro-inflammatory responses that can be detrimental in certain disease states, a dichotomous, protective role of IL-33 in promoting wound healing has also emerged in multiple tissues types. This review will explore the current literature concerning this homeostatic role of IL-33/ST2 in tissue repair and also review its role in uncontrolled wound responses as seen in both fibrosis and tumorigenesis.

Seawater carbonate chemistry and biological processes during experiments with oyster Crassostrea gigas, 2009

An increasing number of studies are now reporting the effects of ocean acidification on a broad range of marine species, processes and systems. Many of these are investigating the sensitive early life-history stages that several major reviews have highlighted as being potentially most susceptible to ocean acidification. Nonetheless there remain few investigations of the effects of ocean acidification on the very earliest, and critical, process of fertilization, and still fewer that have investigated levels of ocean acidification relevant for the coming century. Here we report the effects of near-future levels of ocean acidification (?0.35 pH unit change) on sperm swimming speed, sperm motility, and fertilization kinetics in a population of the Pacific oyster Crassostrea gigas from western Sweden. We found no significant effect of ocean acidification - a result that was well-supported by power analysis. Similar findings from Japan suggest that this may be a globally robust result, and we emphasise the need for experiments on multiple populations from throughout a species' range. We also discuss the importance of sound experimental design and power analysis in meaningful interpretation of non-significant results.

The Narrative Value of Dance Communication: "habitus", musicality and emotion

The richness of dance comes from the need to work with an individual body. Still, the body of the dancer belongs to plural context, crossed by artistic and social traditions, which locate the artists in a given field. We claim that role conflict is an essential component of the structure of collective artistic creativity. We address the production of discourse in a British dance company, with data that spawns from the ethnography ‘Dance and Cognition’, directed by David Kirsh at the University of California, together with WayneMcGregor-Random Dance. Our Critical Discourse Analysis is based on multiple interviews to the dancers and choreographer. Our findings show how creativity in dance seems to be empirically observable, and thus embodied and distributed shaped by the dance habitus of the particular social context.

Of Marx and Makers: an Historical Perspective on Generative Justice

In Marxist frameworks “distributive justice” depends on extracting value through a centralized state. Many new social movements—peer to peer economy, maker activism, community agriculture, queer ecology, etc.—take the opposite approach, keeping value in its unalienated form and allowing it to freely circulate from the bottom up. Unlike Marxism, there is no general theory for bottom-up, unalienated value circulation. This paper examines the concept of “generative justice” through an historical contrast between Marx’s writings and the indigenous cultures that he drew upon. Marx erroneously concluded that while indigenous cultures had unalienated forms of production, only centralized value extraction could allow the productivity needed for a high quality of life. To the contrary, indigenous cultures now provide a robust model for the “gift economy” that underpins open source technological production, agroecology, and restorative approaches to civil rights. Expanding Marx’s concept of unalienated labor value to include unalienated ecological (nonhuman) value, as well as the domain of freedom in speech, sexual orientation, spirituality and other forms of “expressive” value, we arrive at an historically informed perspective for generative justice. 

GPs’ and community pharmacists’ opinions on medication management at transitions of care in Ireland

Objective. The aim of this study was to survey GPs and community pharmacists (CPs) in Ireland regarding current practices of medication management, specifically medication reconciliation, communication between health care providers and medication errors as patients transition in care.
Methods. A national cross-sectional survey was distributed electronically to 2364 GPs, 311 GP Registrars and 2382 CPs. Multivariable associations comparing GPs to CPs were generated and content analysis of free text responses was undertaken.
Results. There was an overall response rate of 17.7% (897 respondents—554 GPs/Registrars and 343 CPs). More than 90% of GPs and CPs were positive about the effects of medication reconciliation on medication safety and adherence. Sixty per cent of GPs reported having no formal system of medication reconciliation. Communication between GPs and CPs was identified as good/very good by >90% of GPs and CPs. The majority (>80%) of both groups could clearly recall prescribing errors, following a transition of care, they had witnessed in the previous 6 months. Free text content analysis corroborated the positive relationship between GPs and CPs, a frustration with secondary care communication, with many examples given of prescribing errors.
Conclusions. While there is enthusiasm for the benefits of medication reconciliation there are limited formal structures in primary care to support it. Challenges in relation to systems that support inter-professional communication and reduce medication errors are features of the primary/secondary care transition. There is a need for an improved medication management system. Future research should focus on the identified barriers in implementing medication reconciliation and systems that can improve it.

E-Government Collaboration in the Swedish Public Sector : Multiple Studies on Collaboration Facilitators and Collaboration Modes

Collaboration in the public sector is imperative to achieve e-government objectives such as improved efficiency and effectiveness of public administration and improved quality of public services. Collaboration across organizational and institutional boundaries requires public organizations to share e-government systems and services through for instance, interoperable information technology and processes. Demands on public organizations to become more open also require that public organizations adopt new collaborative approaches for inviting and engaging citizens in governmental activities. E-government related collaboration in the public sector is challenging, however, and collaboration initiatives often fail. Public organizations need to learn how to collaborate since forms of e-government collaboration and expected outcomes are mostly unknown. How public organizations can collaborate and the expected outcomes are thus investigated in this thesis by studying multiple collaboration cases on the acquisition and implementation of a particular e-government investment (digital archive). This thesis also investigates how e-government collaboration can be facilitated through artifacts. It is done through a case study, where objects that cross boundaries between collaborating communities in the public sector are studied, and by designing a configurable process model integrating several processes for social services. By using design science, this thesis also investigates how an m-government solution that facilitates collaboration between citizens and public organizations can be designed. The thesis contributes to literature through describing five different modes of interorganizational collaboration in the public sector and the expected benefits from each mode. It also contributes with an instantiation of a configurable process model supporting three open social e-services and with evidence of how it can facilitate collaboration. This thesis further describes how boundary objects facilitate collaboration between different communities in an open government design initiative. It contributes with a designed mobile government solution, thereby providing proof of concept and initial design implications for enabling collaboration with citizens through citizen sourcing (outsourcing a governmental activity to citizens through an open call). This thesis also identifies research streams within e-government collaboration research through a literature review and the thesis contributions are related to the identified research streams. This thesis gives directions for future research by suggesting that future research should focus further on understanding e-government collaboration and how information and communication technology can facilitate collaboration in the public sector. It is suggested that further research should investigate m-government solutions to form design theories. Future research should also examine how value can be co-created in e-government collaboration.

Reproductive Patterns and Birth Seasonality in a South-American Breeding Colony of Common Marmosets, Callithrix jacchus

SOUSA,M.B.C. et al. Reproductive Patterns and Birth Seasonality in a South-American Breeding Colony of Common Marmosets, Callithrix jacchus. Primates, v.40, n.2, p. 327-336, Apr. 1999.

Sunray etched Visors for the Jamaican Olympic Team in three colours: yellow, green and black

Design for visors for the delegation from Jamaica to the London Olympic Games 2012. This design was commissioned by PUMA 2012 based on McLean's designs featured in the website House of Flora, which functions as a space of display, archive, folio, point of sale and dissemination. The McLean standard design for visors is a component of the avant garde, pret a porter millinery, accessory design collections, and stylistically customised for the Jamaican team. McLean's oeuvre is original in its integration of the experimental traditions of art school workshop culture with the professional demands of fashion manufacture and trade culture. Combining the innovation of the postmodern urban artisan with the exacting demands of industrial production, dissemination and distribution McLean's design work spans the disparate worlds of national art collections such as the Victoria and Albert Museum (A Hat Anthology Exhibition, and catalogue 2009), London Design Museum ( Fifty Hats that Changed the World 2009). Integrating design considerations of multiple and mass production with the stylistic considerations of the studio workshop McLean brings the wit of the avant garde urban artisan to the structures and systems of fashion industry. The designs reach to a global audience as product users, as well as to the international connoisseurship of crafts and design specialists. The rigour of McLean's research and innovation is evident in the specificity of the stylistic references made through her selection of materials, processes, form, colour and symbolism. A range of cultural references cite the rich fusion of early twentieth century modernist culture in which the disparate worlds of popular, proletarian, culture fertilised the stylistic austerity of high modern formalism. McLean here considers the relationship between millinery and coiffure, following from the millinery piece featured in (Marcel bobbed hairpiece hat), and now brings the considerations of ethnic difference to bear on her design. Afro hair brings user group specificity to the milliner, and the visor design is a resolution of function and style for both protection and display. Connoting the sartorial conventions of workwear headgear, rather than the nineteenth century colonial 'cricketer's' cap, or the twentieth century US 'baseball' peaked cap, McLean's 'Jamaican Olympic Visor' brings distinctively postcolonial meaning to the cultural profile of the heterotopic media space. Designing for the popular culture of Olympic sports, televised and broadcast to global audiences, brings new forms of agency to the fashion designer, and McLan's design deploys a style that is widely recognisable from other popular culture's film and TV depictions of workwear to mark the distinctive tradition of supremacy that black athletes bring to the European traditions of cultural heritage. Supplanting the Arcadian 'laurels' with which winners are, traditionally, crowned, McLean's visor design innovation, suggests that it is not impossible to challenge and transform apparently timeless hierarchies of power and supremacy, so that ex-slaves may also become victors. McLean's fashion designs all work within this reach of fashion towards the carnivalesque inversion of social orderliness through play, display and sartorial activism.

Proprioception in ankle sprain from exercises and bandages

Ankle sprains are the most common injuries in sports, usually causing damage to the lateral ligaments. Recurrence has as usual result permanent instability, and thus loss of proprioception. This fact, together with residual symptoms, is what is known as chronic ankle instability, CAI, or FAI, if it is functional. This problem tries to be solved by improving musculoskeletal stability and proprioception by the application of bandages and performing exercises. The aim of this study has been to review articles (meta-analisis, systematic reviews and revisions) published in 2009-2015 in PubMed, Medline, ENFISPO and BUCea, using keywords such as “sprain instability”, “sprain proprioception”, “chronic ankle instability”. Evidence affirms that there does exist decreased proprioception in patients who suffer from CAI. Rehabilitation exercise regimen is indicated as a treatment because it generates a subjective improvement reported by the patient, and the application of bandages works like a sprain prevention method limiting the range of motion, reducing joint instability and increasing confidence during exercise. As podiatrists we should recommend proprioception exercises to all athletes in a preventive way, and those with CAI or FAI, as a rehabilitation programme, together with the application of bandages. However, further studies should be generated focusing on ways of improving proprioception, and on the exercise patterns that provide the maximum benefit.

Development of a Wireless MEMS Multifunction Sensor System and Field Demonstration of Embedded Sensors for Monitoring Concrete Pavements, TR-637, 2016

Pavements tend to deteriorate with time under repeated traffic and/or environmental loading. By detecting pavement distresses and damage early enough, it is possible for transportation agencies to develop more effective pavement maintenance and rehabilitation programs and thereby achieve significant cost and time savings. The structural health monitoring (SHM) concept can be considered as a systematic method for assessing the structural state of pavement infrastructure systems and documenting their condition. Over the past several years, this process has traditionally been accomplished through the use of wired sensors embedded in bridge and highway pavement. However, the use of wired sensors has limitations for long-term SHM and presents other associated cost and safety concerns. Recently, micro-electromechanical sensors and systems (MEMS) and nano-electromechanical systems (NEMS) have emerged as advanced/smart-sensing technologies with potential for cost-effective and long-term SHM. This two-pronged study evaluated the performance of commercial off-the-shelf (COTS) MEMS sensors embedded in concrete pavement (Final Report Volume I) and developed a wireless MEMS multifunctional sensor system for health monitoring of concrete pavement (Final Report Volume II).

Early stage memory loss interventions: utilization, impact, and the experience of living alone.

Thesis (Ph.D.)--University of Washington, 2016-08

Introduction to the Special Issue on Biomedical and Bioelectronic Circuits for Enhanced Diagnosis and Therapy

The 22 papers in this special issue focus on biomedical and biolectronic circuits for enhanced diagnosis and therapy.