IL-27 receptor signaling regulates CD4+ T cell chemotactic responses during infection.

IL-27 exerts pleiotropic suppressive effects on naive and effector T cell populations during infection and inflammation. Surprisingly, however, the role of IL-27 in restricting or shaping effector CD4(+) T cell chemotactic responses, as a mechanism to reduce T cell-dependent tissue inflammation, is unknown. In this study, using Plasmodium berghei NK65 as a model of a systemic, proinflammatory infection, we demonstrate that IL-27R signaling represses chemotaxis of infection-derived splenic CD4(+) T cells in response to the CCR5 ligands, CCL4 and CCL5. Consistent with these observations, CCR5 was expressed on significantly higher frequencies of splenic CD4(+) T cells from malaria-infected, IL-27R-deficient (WSX-1(-/-)) mice than from infected wild-type mice. We find that IL-27 signaling suppresses splenic CD4(+) T cell CCR5-dependent chemotactic responses during infection by restricting CCR5 expression on CD4(+) T cell subtypes, including Th1 cells, and also by controlling the overall composition of the CD4(+) T cell compartment. Diminution of the Th1 response in infected WSX-1(-/-) mice in vivo by neutralization of IL-12p40 attenuated CCR5 expression by infection-derived CD4(+) T cells and also reduced splenic CD4(+) T cell chemotaxis toward CCL4 and CCL5. These data reveal a previously unappreciated role for IL-27 in modulating CD4(+) T cell chemotactic pathways during infection, which is related to its capacity to repress Th1 effector cell development. Thus, IL-27 appears to be a key cytokine that limits the CCR5-CCL4/CCL5 axis during inflammatory settings

Multicenter Diagnostic Evaluation of OnSite COVID-19 Rapid Test (CTK Biotech) among Symptomatic Individuals in Brazil and the United Kingdom

Evaluating rapid diagnostic tests in diverse populations is essential to improving diagnostic responses as it gives an indication of the accuracy in real-world scenarios. In the case of rapid diagnostic testing within this pandemic, lateral flow tests that meet the minimum requirements for sensitivity and specificity can play a key role in increasing testing capacity, allowing timely clinical management of those infected, and protecting health care systems

FLOW, LIMINALITY, AND EUDAIMONIA: PAGAN RITUAL PRACTICE AS A GATEWAY TO A LIFE WITH MEANING

Paganism is a term applied to a number of nature religions based on traditional indigenous practices. Paganism is practiced through rituals designed to facilitate a flow state that allows practitioners to use magic to achieve their aims. Since the introduction of Wicca to mainstream society in the 1950s, many other Pagan traditions have developed. Similarly, the number of people identifying as Pagan has also increased; in 2011 the number of people identifying as Pagan in the UK census reached 80,153. Despite this growth, Paganism is a topic that is under researched in Psychology. This paper uses Ryff’s theory of Psychological well-being as a frame work through which to explore the ways in which Paganism may be particularly conducive to eudemonic well-being as a result of the flow experiences inherent in its practice. This theory posits six key dimensions of eudaimonia; personal growth, self-acceptance, positive relation with others, autonomy, environmental mastery, and purpose in life. The ways in which each of these dimensions is elicited through Paganism is elucidated

Parasite-specific CD4+IFN-γ+IL-10+ T cells distribute within both lymphoid and non-lymphoid compartments and are controlled systemically by IL-27 and ICOS during blood-stage malaria infection.

Immune-mediated pathology in interleukin-10 (IL-10)-deficient mice during blood-stage malaria infection typically manifests in nonlymphoid organs, such as the liver and lung. Thus, it is critical to define the cellular sources of IL-10 in these sensitive nonlymphoid compartments during infection. Moreover, it is important to determine if IL-10 production is controlled through conserved or disparate molecular programs in distinct anatomical locations during malaria infection, as this may enable spatiotemporal tuning of the regulatory immune response. In this study, using dual gamma interferon (IFN-γ)–yellow fluorescent protein (YFP) and IL-10–green fluorescent protein (GFP) reporter mice, we show that CD4(+) YFP(+) T cells are the major source of IL-10 in both lymphoid and nonlymphoid compartments throughout the course of blood-stage Plasmodium yoelii infection. Mature splenic CD4(+) YFP(+) GFP(+) T cells, which preferentially expressed high levels of CCR5, were capable of migrating to and seeding the nonlymphoid tissues, indicating that the systemically distributed host-protective cells have a common developmental history. Despite exhibiting comparable phenotypes, CD4(+) YFP(+) GFP(+) T cells from the liver and lung produced significantly larger quantities of IL-10 than their splenic counterparts, showing that the CD4(+) YFP(+) GFP(+) T cells exert graded functions in distinct tissue locations during infection. Unexpectedly, given the unique environmental conditions within discrete nonlymphoid and lymphoid organs, we show that IL-10 production by CD4(+) YFP(+) T cells is controlled systemically during malaria infection through IL-27 receptor signaling that is supported after CD4(+) T cell priming by ICOS signaling. The results in this study substantially improve our understanding of the systemic IL-10 response to malaria infection, particularly within sensitive nonlymphoid organs

Study of soft magnetic thin films and patterned devices with MOKE imaging technique

While the conventional microelectronic integrated circuits based on the electron charge are approaching the theoretical limitation in foreseeable future, next generation nonvolatile logic units based on electron spin have potential to build logic networks of low-power consumption. Central to this work is to investigate the magnetic properties of soft magnetic materials and develop a method for in-memory computing based on patterned soft magnetic materials logic units. The mainly result were carried out by Magneto-optical Kerr effect (MOKE) microscopy. By inverting the growth order, the amount of defects can be artificially tuned, and skyrmions are shown to be preferentially formed in samples with more defects. The stable region and the density of the skyrmions can be efficiently controlled in the return magnetization loops by utilizing first-order reversal curves (FORCs). The major contribution of these findings establish a general internal link from sample preparation to skyrmion generation and provides a general method for controlling skyrmion density. Next, the temperature-dependent magnetic properties of MgO/CoFeB/Ta thin films have been investigated. The perpendicular magnetic anisotropy (PMA) gradient in MgO/CoFeB/Ta thin films via the temperature gradient generation sample stage has been studied. This study provides a new easy method to create a PMA gradient that will contribute to the simplification of field-free spintronic devices. Eventually, Y-shaped NiFe nanowire has been investigated. The quasi-static micromagnetic simulations correspond to the experimental results and reveal the principle of device operations. The use of programmable logic units and potential applications for in-memory computing have been further extended based on this nanostructure. The major contribution of this part proposes a feasible paradigm for in-memory computing programmable logic gate, which can significantly reduce the complexity of conventional logic circuits. The results conclusion and discussion for the future works are proposed in the final chapter

WISP1/CCN4: A Potential Target for Inhibiting Prostate Cancer Growth and Spread to Bone

Prostate cancer (PC) is a leading cause of death in men however the factors that regulate its progression and eventual metastasis to bone remain unclear. Here we show that WISP1/CCN4 expression in prostate cancer tissues was up-regulated in early stages of the disease and, further, that it correlated with increased circulating levels of WISP1 in the sera of patients at early stages of the disease. WISP1 was also elevated in the mouse prostate cancer model TRAMP in the hypoplastic diseased tissue that develops prior to advanced carcinoma formation. When the ability of anti-WISP1 antibodies to reduce the spread of PC3-Luc cells to distant sites was tested it showed that twice weekly injections of anti-WISP1 antibodies reduced the number and overall size of distant tumors developed after intracardiac (IC) injection of PC3-Luc cells in mice. The ability of antibodies against WISP1 to inhibit growth of PC3-Luc cancer cells in mice was also evaluated and showed that twice weekly injections of anti-WISP1 antibodies reduced local tumor growth when examined in xenografts. To better understand the mechanism of action, the migration of PC3-Luc cells through membranes with or without a Matrigel™ barrier showed the cells were attracted to WISP1, and that this attraction was inhibited by treatment with anti-WISP1 antibodies. We also show the expression of WISP1 at the bone-tumor interface and in the stroma of early grade cancers suggested WISP1 expression is well placed to play roles in both fostering growth of the cancer and its spread to bone. In summary, the up-regulation of WISP1 in the early stages of cancer development coupled with its ability to inhibit spread and growth of prostate cancer cells makes it both a potential target and an accessible diagnostic marker for prostate cancer