Microglia and Astrocyte Activation by Toll-Like Receptor Ligands: Modulation by PPAR-γ Agonists

Microglia and astrocytes express numerous members of the Toll-like receptor (TLR) family that are pivotal for recognizing conserved microbial motifs expressed by a wide array of pathogens. Despite the critical role for TLRs in pathogen recognition, when dysregulated these pathways can also exacerbate CNS tissue destruction. Therefore, a critical balance must be achieved to elicit sufficient immunity to combat CNS infectious insults and downregulate these responses to avoid pathological tissue damage. We performed a comprehensive survey on the efficacy of various PPAR-γ agonists to modulate proinflammatory mediator release from primary microglia and astrocytes in response to numerous TLR ligands relevant to CNS infectious diseases. The results demonstrated differential abilities of select PPAR-γ agonists to modulate glial activation. For example, 15d-PGJ2 and pioglitazone were both effective at reducing IL-12 p40 release by TLR ligand-activated glia, whereas CXCL2 expression was either augmented or inhibited by 15d-PGJ2, effects that were dependent on the TLR ligand examined. Pioglitazone and troglitazone demonstrated opposing actions on microglial CCL2 production that were TLR ligand-dependent. Collectively, this information may be exploited to modulate the host immune response during CNS infections to maximize host immunity while minimizing inappropriate bystander tissue damage that is often characteristic of such diseases

Microglia and Astrocyte Activation by Toll-Like Receptor Ligands: Modulation by PPAR-gamma Agonists.

Microglia and astrocytes express numerous members of the Toll-like receptor (TLR) family that are pivotal for recognizing conserved microbial motifs expressed by a wide array of pathogens. Despite the critical role for TLRs in pathogen recognition, when dysregulated these pathways can also exacerbate CNS tissue destruction. Therefore, a critical balance must be achieved to elicit sufficient immunity to combat CNS infectious insults and downregulate these responses to avoid pathological tissue damage. We performed a comprehensive survey on the efficacy of various PPAR-gamma agonists to modulate proinflammatory mediator release from primary microglia and astrocytes in response to numerous TLR ligands relevant to CNS infectious diseases. The results demonstrated differential abilities of select PPAR-gamma agonists to modulate glial activation. For example, 15d-PGJ(2) and pioglitazone were both effective at reducing IL-12 p40 release by TLR ligand-activated glia, whereas CXCL2 expression was either augmented or inhibited by 15d-PGJ(2), effects that were dependent on the TLR ligand examined. Pioglitazone and troglitazone demonstrated opposing actions on microglial CCL2 production that were TLR ligand-dependent. Collectively, this information may be exploited to modulate the host immune response during CNS infections to maximize host immunity while minimizing inappropriate bystander tissue damage that is often characteristic of such diseases

Analyses of teachers' perceptions and attitudes of a teacher laptop initiative

This study analyzed the attitudes and perceptions of teachers following the implementation of a teacher laptop initiative. The attitudes and perceptions were documented through a mixed-methods research design that collected both quantitative and qualitative data. Quantitative data were gathered using pretest and posttest surveys. Qualitative data were gathered through focus group interviews and were used to further inform the quantitative data. The quantitative data suggested that a teacher laptop initiative can affect attitudes and perceptions of teachers. Participants in this study increased their overall perception of their computer use and began to adopt technology in the classroom by using it more often. Results suggested that teachers became more comfortable with computers when given a laptop. The quantitative data did not show significance between a teacher laptop initiative and teacher interest toward computers and teacher view of computer significance. This research also suggested that a teacher laptop initiative, coupled with professional development, can better prepare students for the 21st century. An implication of this study was if teachers are given resources and proper training on how to implement technology in the classroom, attitudes and classroom practices can be changed. Participants believed if educators begin to integrate technology in the classroom and model skills for students, technology could help prepare students for the 21st century

Adipose tissue macrophages in insulin-resistant subjects are associated with collagen VI and fibrosis and demonstrate alternative activation

Adipose tissue macrophages are associated with insulin resistance and are linked to changes in the extracellular matrix. To better characterize adipose macrophages, the extracellular matrix, and adipocyte-macrophage interactions, gene expression from adipose tissue and the stromal vascular fraction was assessed for markers of inflammation and fibrosis, and macrophages from obese and lean subjects were counted and characterized immunohistochemically. Coculture experiments examined the effects of adipocyte-macrophage interaction. Collagen VI gene expression was associated with insulin sensitivity and CD68 (r = −0.56 and 0.60, P < 0.0001) and with other markers of inflammation and fibrosis. Compared with adipose tissue from lean subjects, adipose tissue from obese subjects contained increased areas of fibrosis, which correlated inversely with insulin sensitivity (r = −0.58, P < 0.02) and positively with macrophage number (r = 0.70, P < 0.01). Although macrophages in crownlike structures (CLS) were more abundant in obese adipose tissue, the majority of macrophages were associated with fibrosis and were not organized in CLS. Macrophages in CLS were predominantly M1, but most other macrophages, particularly those in fibrotic areas, were M2 and also expressed CD150, a marker of M2c macrophages. Coculture of THP-1 macrophages with adipocytes promoted the M2 phenotype, with a lower level of IL-1 expression and a higher ratio of IL-10 to IL-12. Transforming growth factor-β (TGF-β) was more abundant in M2 macrophages and was further increased by coculture with adipocytes. Downstream effectors of TGF-β, such as plasminogen activator inhibitor-1, collagen VI, and phosphorylated Smad, were increased in macrophages and adipocytes. Thus adipose tissue of insulin-resistant humans demonstrated increased fibrosis, M2 macrophage abundance, and TGF-β activity

Analyses of teachers' perceptions and attitudes of a teacher laptop initiative

This study analyzed the attitudes and perceptions of teachers following the implementation of a teacher laptop initiative. The attitudes and perceptions were documented through a mixed-methods research design that collected both quantitative and qualitative data. Quantitative data were gathered using pretest and posttest surveys. Qualitative data were gathered through focus group interviews and were used to further inform the quantitative data. The quantitative data suggested that a teacher laptop initiative can affect attitudes and perceptions of teachers. Participants in this study increased their overall perception of their computer use and began to adopt technology in the classroom by using it more often. Results suggested that teachers became more comfortable with computers when given a laptop. The quantitative data did not show significance between a teacher laptop initiative and teacher interest toward computers and teacher view of computer significance. This research also suggested that a teacher laptop initiative, coupled with professional development, can better prepare students for the 21st century. An implication of this study was if teachers are given resources and proper training on how to implement technology in the classroom, attitudes and classroom practices can be changed. Participants believed if educators begin to integrate technology in the classroom and model skills for students, technology could help prepare students for the 21st century. (Published By University of Alabama Libraries