Tetraspanin CD82 Organizes Dectin-1 into Signaling Domains to Mediate Cellular Responses to Candida albicans.

Tetraspanins are a family of proteins possessing four transmembrane domains that help in lateral organization of plasma membrane proteins. These proteins interact with each other as well as other receptors and signaling proteins, resulting in functional complexes called "tetraspanin microdomains." Tetraspanins, including CD82, play an essential role in the pathogenesis of fungal infections. Dectin-1, a receptor for the fungal cell wall carbohydrate ß-1,3-glucan, is vital to host defense against fungal infections. The current study identifies a novel association between tetraspanin CD82 and Dectin-1 on the plasma membrane of Candida albicans-containing phagosomes independent of phagocytic ability. Deletion of CD82 in mice resulted in diminished fungicidal activity, increased C. albicans viability within macrophages, and decreased cytokine production (TNF-α, IL-1ß) at both mRNA and protein level in macrophages. Additionally, CD82 organized Dectin-1 clustering in the phagocytic cup. Deletion of CD82 modulates Dectin-1 signaling, resulting in a reduction of Src and Syk phosphorylation and reactive oxygen species production. CD82 knockout mice were more susceptible to C. albicans as compared with wild-type mice. Furthermore, patient C. albicans-induced cytokine production was influenced by two human CD82 single nucleotide polymorphisms, whereas an additional CD82 single nucleotide polymorphism increased the risk for candidemia independent of cytokine production. Together, these data demonstrate that CD82 organizes the proper assembly of Dectin-1 signaling machinery in response to C. albicans.

Incorporating sleep medicine content into medical school through neuroscience core curricula.

OBJECTIVE: To present (1) justification for earmarking sleep medicine education as an essential component of all medical school curricula and (2) various avenues to incorporate sleep medicine exposure into medical school curricula through (primarily) neuroscience and neurology courses. METHODS: Per consensus of a team of leading neurology and sleep medicine educators, an evidence-based rationale for including sleep medicine across a 4-year medical school curriculum is presented along with suggested content, available/vetted resources, and formats for delivering sleep medicine education at various points and through various formats. RESULTS: Growing evidence has linked sleep disorders (e.g., sleep-disordered breathing, chronic insufficient sleep) as risk factors for several neurologic disorders. Medical educators in neurology/neuroscience are now strongly advocating for sleep medicine education in the context of neurology/neuroscience pre and post graduate medical education. Sleep medicine education is also a critical component of a proactive strategy to address physician wellness and burnout. The suggested curriculum proposes a sleep educational exposure time of 2-4 hours per year in the form of lectures, flipped-classroom sessions, clinical opportunities, and online educational tools that would result in a 200%-400% increase in the amount of sleep medicine exposure that US medical schools currently provide. The guidelines are accompanied by the recommendation for use of technological education, to facilitate more seamless curricular incorporation. CONCLUSION: Even in this era with limited flexibility to add content to an already packed medical school curriculum, incorporating sleep medicine exposure into the current medical school curriculum is both justified and feasible.