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Regulation of neuroinflammation is critical for maintaining central nervous system (CNS) homeostasis and holds therapeutic promise in autoimmune diseases such as multiple sclerosis (MS). Previous studies have highlighted the significance of selective innate signaling in triggering anti-inflammatory mechanisms, which play a protective role in an MS-like disease, experimental autoimmune encephalomyelitis (EAE). However, the individual intra-CNS administration of specific innate receptor ligands or agonists, such as for toll-like receptor 7 (TLR7) and nucleotide-binding oligomerization-domain-containing protein 2 (NOD2), failed to elicit the desired anti-inflammatory response in EAE. In this study, we investigated the potential synergistic effect of targeting both TLR7 and NOD2 simultaneously to prevent EAE progression. Our findings demonstrate that simultaneous intrathecal administration of NOD2- and TLR7-agonists led to synergistic induction of Type I IFN (IFN I) and effectively suppressed EAE in an IFN I-dependent manner. Suppression of EAE was correlated with a significant decrease in the infiltration of monocytes, granulocytes, and natural killer cells, reduced demyelination, and downregulation of IL-1β, CCL2, and IFNγ gene expression in the spinal cord. These results underscore the therapeutic promise of concurrently targeting the TLR7 and NOD2 pathways in alleviating neuroinflammation associated with MS, paving the way for novel and more efficacious treatment strategies. [ABSTRACT FROM AUTHOR]

Pulmonary surfactant protein D (SP-D) is a host defence lectin of the innate immune system that enhances clearance of pathogens and modulates inflammatory responses. Recently it has been found that systemic SP-D is associated with metabolic disturbances and that SP-D deficient mice are mildly obese. However, the mechanism behind SP-D's role in energy metabolism is not known.Here we report that SP-D deficient mice had significantly higher ad libitum energy intake compared to wild-type mice and unchanged energy expenditure. This resulted in accumulation but also redistribution of fat tissue. Blood pressure was unchanged. The change in energy intake was unrelated to the basal levels of hypothalamic Pro-opiomelanocortin (POMC) and Agouti-related peptide (AgRP) gene expression. Neither short time systemic, nor intracereberoventricular SP-D treatment altered the hypothalamic signalling or body weight accumulation.In ad libitum fed animals, serum leptin, insulin, and glucose were significantly increased in mice deficient in SP-D, and indicative of insulin resistance. However, restricted diets eliminated all metabolic differences except the distribution of body fat. SP-D deficiency was further associated with elevated levels of systemic bacterial lipopolysaccharide.In conclusion, our findings suggest that lack of SP-D mediates modulation of food intake not directly involving hypothalamic regulatory pathways. The resulting accumulation of adipose tissue was associated with insulin resistance. The data suggest SP-D as a regulator of energy intake and body composition and an inhibitor of metabolic endotoxemia. SP-D may play a causal role at the crossroads of inflammation, obesity, and insulin resistance.

Through a comparative case study, Sheridan and colleagues explore how makerspaces may function as learning environments. Drawing on field observations, interviews, and analysis of artifacts, videos, and other documents, the authors describe features of three makerspaces and how participants learn and develop through complex design and making practices. They describe how the makerspaces help individuals identify problems, build models, learn and apply skills, revise ideas, and share new knowledge with others. The authors conclude with a discussion of the implications of their findings for this emergent field.

The 2008 commercial video game "Spore" allowed more than a million players to design their own life forms. Starting from single-celled organisms players played through a caricature of natural history. Press coverage of the game's release offer two frames for thinking about the implications of the game. Some scientists and educators saw the game as a troubling teacher of intelligent design, while others suggested it might excite public interest in science. This paper explores the extent to which these two ways of thinking about the game are consistent with what players have done with the game in its online community. This analysis suggests that, at least for the players participating in this community, the game has not seduced them into believing in intelligent design. Instead the activities of these players suggest that the game has played a catalytic role in engaging the public with science. These findings indicate that designers of educational games may wish to consider more deeply tensions between prioritizing accuracy of content in educational games over player engagement.

One of the first places children encounter science and scientists is children's literature. Children's books about science and scientists have, however, received limited scholarly attention. By exploring the history of children's biographies of Marie Curie and Albert Einstein, the two most written about scientist in children's literature, this paper taps this unutilized resource to cultivate a unique perspective on the history of gender and authority in science and science education. Through analysis of explicit discussions of womanhood and science and implicit gendering of Curie and Einstein's school experiences within these books, this study demonstrates that while much has changed in how these stories are framed the gender of the scientist is still central to how they are represented in children's literature.

James Morrison's interview with Trevor Owens explores Zotero, a free, open-source bibliographic tool that works as a Firefox plug-in. Previous bibliographic software, such as EndNote or Refworks, worked either online or offline to collect references and citations. Zotero leverages the power of the browser to allow users to work either online or offline and integrates citations with other research materials in a way that promises to reshape the way research is done. Zotero 2.0, due out in early 2008, will expand the potential of Zotero by providing server-side functions that allow for the sharing of bibliographies and accompanying annotations. (Contains 2 figures.)