Vertebrate skin is characterized by its patterned array of appendages, whether feathers, hairs, or scales. In avian skin the distribution of feathers occurs on two distinct spatial levels. Grouping of feathers within discrete tracts, with bare skin lying between the tracts, is termed the macropattern, while the smaller scale periodic spacing between individual feathers is referred to as the micropattern. The degree of integration between the patterning mechanisms that operate on these two scales during development and the mechanisms underlying the remarkable evolvability of skin macropatterns are unknown. A striking example of macropattern variation is the convergent loss of neck feathering in multiple species, a trait associated with heat tolerance in both wild and domestic birds. In chicken, a mutation called Naked neck is characterized by a reduction of body feathering and completely bare neck. Here we perform genetic fine mapping of the causative region and identify a large insertion associated with the Naked neck trait. A strong candidate gene in the critical interval, BMP12/GDF7, displays markedly elevated expression in Naked neck embryonic skin due to a cis-regulatory effect of the causative mutation. BMP family members inhibit embryonic feather formation by acting in a reaction-diffusion mechanism, and we find that selective production of retinoic acid by neck skin potentiates BMP signaling, making neck skin more sensitive than body skin to suppression of feather development. This selective production of retinoic acid by neck skin constitutes a cryptic pattern as its effects on feathering are not revealed until gross BMP levels are altered. This developmental modularity of neck and body skin allows simple quantitative changes in BMP levels to produce a sparsely feathered or bare neck while maintaining robust feather patterning on the body.
Studies of the immune response in chronic helminth infections suggest that parasites modulate the host's immune response. Taenia solium metacestodes, in particular, produce molecules that down-regulate cell-mediated immunity. We have described a small RNA peptide termed metacestode factor (MF) that depresses the murine immune response to Salmonella typhimurium antigens. MF inhibits mitogen-induced proliferation, humoral and cellular responses to metacestode antigens, and inflammation surrounding metacestodes implanted subcutaneously in mice. To assess the effects of MF on cytokine production we stimulated murine spleen cells in vitro with concanavalin A and measured cytokine concentrations in the culture supernatants by enzyme-linked immunosorbent assay. When cultured with MF, the cells showed significantly decreased production of interleukin 2 (IL-2), interferon-gamma (IFN-gamma), and IL-4 as compared with mitogen alone. Exogenous rIL-2 and rIL-4 largely restored the proliferative response (85% and 71% of control cells, respectively). MF also decreased production of tumor necrosis factor-alpha (TNF-alpha) by macrophages stimulated with lipopolysaccharide and IFN-gamma. The TNF-alpha concentration was inversely correlated with the MF concentration. Experiments using spleen cells from mice treated with MF also showed a significant reduction in IL-4 concentration. These results suggest that MF inhibits cytokine production without regard to cell type or cytokine. This may explain the function of this molecule as an inhibitor of the host inflammatory and immune responses.
Abstract. To detect IgG antibodies to Taenia solium, a controlled double-blind study was conducted using 91 coded cerebrospinal fluid samples from patients with neurocysticercosis (NCC) and other neurologic disorders. Samples were tested in an enzyme-linked immunosorbent assay (ELISA) using metacestode excretion/secretion antigens. The results were correlated with data from medical records on the diagnosis of NCC (based on computed tomography and magnetic resonance imaging criteria) and other neurologic disorders. The ELISA results were positive in 22 of the 24 cases with active NCC. In contrast, six cases with calcified cysts (inactive NCC), as well as one case in a transitional stage, were negative. One case with a calcified granuloma and another with a granuloma plus calcifications (classified as inactive NCC) had positive results. The remaining negative results corresponded to other neurologic disorders (58 cases). The results of the ELISA showed a significant difference between active and inactive NCC (P ס 0.0034).
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