Chronic wounds affect 12–15% of patients with diabetes and are associated with a drastic decrease in their quality of life. Here we demonstrate that purified mature naïve B220+/CD19+/IgM+/IgD+ B cells improve healing of acute and diabetic murine wounds after a single topical application. B cell treatment significantly accelerated acute wound closure by 2–3 days in wild-type mice and 5–6 days in obese diabetic mice. The treatment led to full closure in 43% of chronic diabetic wounds, as compared to only 5% in saline-treated controls. Applying equivalent numbers of T cells or disrupted B cells failed to reproduce these effects, indicating that live B cells mediated pro-healing responses. Topically-applied B cell treatment was associated with significantly reduced scar size, increased collagen deposition and maturation, enhanced angiogenesis and increased nerve growth into and under the healing wound. β-III tubulin+ nerve endings in scars of wounds treated acutely with B cells showed increased relative expression of growth-associated protein 43. The improved healing associated with B cell treatment was supported by significantly increased fibroblast proliferation and decreased apoptosis in the wound bed and edges, altered kinetics of neutrophil infiltration, as well as an increase in TGF-β and a significant reduction in MMP2 expression in wound granulation tissue. Our findings indicate that the timeline and efficacy of wound healing can be experimentally manipulated through the direct application of mature, naive B cells, which effectively modify the balance of mature immune cell populations within the wound microenvironment and accelerate the healing process.
The weakly electric fish Apteronotus leptorhynchus produces wave-like electric organ discharges distinguished by a high degree of regularity. Transient amplitude and frequency modulations ("chirps") can be evoked in males by stimulation with the electric field of a conspecific. During these interactions, the males examined in this study produced six types of chirps, including two novel ones. Stimulation of a test fish with a conspecific at various distances showed that two electrically interacting fish must be within 10 cm of each other to evoke chirping behavior in the neighboring fish. The chirp rate of all but one chirp type elicited by the neighboring fish was found to be negatively correlated with the absolute value of the frequency difference between the two interacting fish, but independent of the sign of this difference. Correlation analysis of the instantaneous rates of chirp occurrence revealed two modes of interactions characterized by reciprocal stimulation and reciprocal inhibition. Further analysis of the temporal relationship between the chirps generated by the two fish during electric interactions showed that the chirps generated by one individual follow the chirps of the other with a short latency of approximately 500-1,000 ms. We hypothesize that this "echo response" serves a communicatory function.
In contrast to mammals, teleost fish exhibit an enormous potential to regenerate adult spinal cord tissue after injury. However, the mechanisms mediating this ability are largely unknown. Here, we analyzed the major processes underlying structural and functional regeneration after amputation of the caudal portion of the spinal cord in Apteronotus leptorhynchus, a weakly electric teleost. After a transient wave of apoptotic cell death, cell proliferation started to increase 5 days after the lesion and persisted at high levels for at least 50 days. New cells differentiated into neurons, glia, and ependymal cells. Retrograde tract tracing revealed axonal re-growth and innervation of the regenerate. Functional regeneration was demonstrated by recovery of the amplitude of the electric organ discharge, a behavior generated by spinal motoneurons. Computer simulations indicated that the observed rates of apoptotic cell death and cell proliferation can adequately explain the re-growth of the spinal cord.
The social nature of termites has allowed them to become an ecologically dominant taxon. However, their nesting and foraging habits (decayed wood and/or soil), combined with frequent social interactions, enhances the risk of pathogen transmission. New dispersing kings and queens are especially vulnerable to pathogens due to the metabolic demands of nest construction, courtship, mating, oogenesis, and parental care, all while mounting an immune response to novel pathogens encountered upon leaving the natal nest. To quantify differential allocation of resources during colony establishment in response to disease exposure, Zootermopsis angusticollis kings and queens were paired after one or both individuals received an injection of saline, heat-killed Serratia marcescens (ecologically relevant, Gram-negative, soil bacterium), a sub-lethal dose of live S. marcescens, or were left untreated. We then quantified several indices of fitness, including the survival of the reproductive pair, onset and likelihood of oviposition, number of eggs produced, and egg quality as a function of parental immunological treatment. Our results uncovered complex and dynamic interactions between these fitness measures and pathogenic stress. Overall, pathogenic stress reduced the survival of kings and queens, the likelihood of oviposition and egg total, but not the onset of oviposition or egg quality, indicating that, in the face of disease, queens "opt" to maintain offspring quality over quantity. These impacts appear to be context-dependent-modulated by colony of origin, sex, mass, and the presence of a mate-rather than absolute. The acquisition of resources prior to colony foundation, combined with the effects of pathogenic exposure, can dramatically limit the success of termites. Based on these empirical data, we have developed a conceptual model of the first 30 days of colony life, involving two successive fitness checkpoints, survival and oviposition, followed by an initial growth phase in which the first egg cohort is produced. In summary, we identified not only the intrinsic and extrinsic factors that influence successful termite colony foundation, but also the maternal and paternal pathogen-induced effects. Such effects alter resource allocation decisions of parents toward their offspring, with cascading consequences on colony fitness.
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