3 resultados para New paradigm
em Duke University
Resumo:
A key challenge in promoting decent work worldwide is how to improve the position of both firms and workers in value chains and global production networks driven by lead firms. This article develops a framework for analysing the linkages between the economic upgrading of firms and the social upgrading of workers. Drawing on studies which indicate that firm upgrading does not necessarily lead to improvements for workers, with a particular focus on the Moroccan garment industry, it outlines different trajectories and scenarios to provide a better understanding of the relationship between economic and social upgrading. The authors 2011 Journal compilation © International Labour Organization 2011.
Resumo:
Natural IgM (nIgM) is constitutively present in the serum, where it aids in the early control of viral and bacterial expansions. nIgM also plays a significant role in the prevention of autoimmune disease by promoting the clearance of cellular debris. However, the cells that maintain high titers of nIgM in the circulation had not yet been identified. Several studies have linked serum nIgM with the presence of fetal-lineage B cells, and others have detected IgM secretion directly by B1a cells in various tissues. Nevertheless, a substantial contribution of undifferentiated B1 cells to nIgM titers is doubtful, as the ability to produce large quantities of antibody (Ab) is a function of the phenotype and morphology of differentiated plasma cells (PCs). No direct evidence exists to support the claim that a B1-cell population directly produces the bulk of circulating nIgM. The source of nIgM thus remained uncertain and unstudied.
In the first part of this study, I identified the primary source of nIgM. Using enzyme-linked immunosorbent spot (ELISPOT) assay, I determined that the majority of IgM Ab-secreting cells (ASCs) in naïve mice reside in the bone marrow (BM). Flow cytometric analysis of BM cells stained for intracellular IgM revealed that nIgM ASCs express IgM and the PC marker CD138 on their surface, but not the B1a cell marker CD5. By spinning these cells onto slides and staining them, following isolation by fluorescence-activated cell sorting (FACS), I found that they exhibit the typical morphological characteristics of terminally differentiated PCs. Transfer experiments demonstrated that BM nIgM PCs arise from a progenitor in the peritoneal cavity (PerC), but not isolated PerC B1a, B1b, or B2 cells. Immunoglobulin (Ig) gene sequence analysis and examination of B1-8i mice, which carry an Ig knockin that prohibits fetal B-cell development, indicated that nIgM PCs differentiate from fetal-lineage B cells. BrdU uptake experiments showed that the nIgM ASC compartment contains a substantial fraction of long-lived plasma cells (LLPCs). Finally, I demonstrated that nIgM PCs occupy a survival niche distinct from that used by IgG PCs.
In the second part of this dissertation, I characterized the unique survival niche of nIgM LLPCs, which maintain constitutive high titers of nIgM in the serum. By using genetically deficient or Ab-depleted mice, I found that neither T cells, type 2 innate lymphoid cells, nor mast cells, the three major hematopoietic producers of IL-5, were required for nIgM PC survival in the BM. However, IgM PCs associate strongly with IL-5-expressing BM stromal cells, which support their survival in vitro when stimulated. In vivo neutralization of IL-5 revealed that, like individual survival factors for IgG PCs, IL-5 is not the sole supporter of IgM PCs, but is likely one of several redundant molecules that together ensure uninterrupted signaling. Thus, the long-lived nIgM PC niche is not composed of hematopoietic sources of IL-5, but a stromal cell microenvironment that provides multiple redundant survival signals.
In the final part of my study, I identified and characterized the precursor of nIgM PCs, which I found in the first project to be resident in the PerC, but not a B1a, B1b, or B2 cell. By transferring PerC cells sorted based on expression of CD19, CD5, and CD11b, I found that only the CD19+CD5+CD11b- population contained cells capable of differentiating into nIgM PCs. Transfer of decreasing numbers of unfractionated PerC cells into Rag1 knockouts revealed an order-of-magnitude drop in the rate of serum IgM reconstitution between stochastically sampled pools of 106 and 3x105 PerC cells, suggesting that the CD19+CD5+CD11b- compartment comprises two cell types, and that interaction between the two necessary for nIgM-PC differentiation. By transferring neonatal liver, I determined that the early hematopoietic environment is required for nIgM PC precursors to develop. Using mice carrying a mutation that disturbs cKit expression, I also found that cKit appears to be required at a critical point near birth for the proper development of nIgM PC precursors.
The collective results of these studies demonstrate that nIgM is the product of BM-resident PCs, which differentiate from a PerC B cell precursor distinct from B1a cells, and survive long-term in a unique survival niche created by stromal cells. My work creates a new paradigm by which to understand nIgM, B1 cell, and PC biology.
Resumo:
This dissertation attempts to retrieve the integration of prayer and theology in the life of the church. Prayer is a spiritual and bodily theological activity that forms Christian identity and virtuous character. The bodily dimension of Christian prayer plays an essential role in theological understanding and moral formation. However, the embodiment of prayer has been mostly neglected in modern academic theology. This study highlights the significance of the body at prayer in theological studies and spiritual formation.
Chapter 1 presents Karl Barth’s theology of prayer as a model of the integration of prayer, theology, and Christian life (lex orandi, lex credendi, lex agendi). However, Barth’s attempt to overcome the dichotomy between theory and practice in theology did not pay much attention to embodiment of prayer. Through ritual studies and phenomenology (Marcel Mauss, Maurice Merleau-Ponty, and Pierre Bourdieu), chapter 2 shows why the bodily dimension of the practice of prayer should be recovered in theology and ministry; then it explains how Christians in the early and medieval church actually prayed with the body, how their bodily actions were understood in their theological paradigms, and how their actions contributed to the formation of Christian character. Chapter 3 narrows the focus to the formation of the heart in the making of Christian character. The practice of prayer has been emphasized not only as an expression of the inner heart of pray-ers but also as a channel of grace that shapes their affections as enduring dispositions of the heart. Furthermore, historically the bodily practice of prayer gave theological authority to the devout Christians who were marginalized in academic theology or ecclesiastical hierarchy, and Chapter 4 presents the lex orandi of praying women who gained their theological knowledge, wisdom, and authority through their exemplary practices of prayer (Catherine of Siena, Mechthild of Magdeburg, Julian of Norwich, Margery Kempe, and Teresa of Avila). These historical examples reveal how Christian communities appreciated and celebrated the theological voices from the margins, which developed from theological embodiments in prayer.
This dissertation concludes that academic theology needs to heed these diverse theological voices, which are nurtured through everyday practice, as an integral part of theological studies. Therefore, it calls for a new paradigm for understanding the relationship between theory and practice in theological education. The integration between theory and bodily practice is necessary for both academic theology and spiritual formation. A more holistic understanding of Christian practices will not only enhance the training of scholars and clergy but also give the laity their own theological voices that will enrich academic theology.