The Effects of Isolation on the Sensitization and Habituation of Aggression in the Threespine Stickleback (Gasterosteus aculeatus)

Our previous research showed that territorial threespine sticklebacks are more aggressive toward a male conspecific placed in their territory if they have been housed adjacent to a gravid female rather than a male or a nongravid female. This study replicated the condition of a territorial male with an adjacently housed male and compared the results with isolated territorial males. This permitted us to contrast explanations for the increased aggression when the neighbor was a gravid female. If the social context determines the level of aggression, then males with no neighbors (isolates) might be less aggressive because there would be no unique reproductive resource to protect nor any neighbor to protect resources from. Alternatively, if aggression is higher in the isolated group it might be because there was no male neighbor to redirect aggression toward. We found that isolated males were more aggressive toward an intruded male stimulus than males with a male neighbor. The study also provided evidence that sensitization produced by the appearance of an intruding male energizes other aggressive behavior, but not those related to feeding, nor does it cause increase in general activation as measured by increased locomotion.     

High-resolution optical coherence tomographic imaging of osteoarthritic cartilage during open knee surgery

This study demonstrates the first real-time imaging in vivo of human cartilage in normal and osteoarthritic knee joints at a resolution of micrometers, using optical coherence tomography (OCT). This recently developed high-resolution imaging technology is analogous to B-mode ultrasound except that it uses infrared light rather than sound. Real-time imaging with 11-μm resolution at four frames per second was performed on six patients using a portable OCT system with a handheld imaging probe during open knee surgery. Tissue registration was achieved by marking sites before imaging, and then histologic processing was performed. Structural changes including cartilage thinning, fissures, and fibrillations were observed at a resolution substantially higher than is achieved with any current clinical imaging technology. The structural features detected with OCT were evident in the corresponding histology. In addition to changes in architectural morphology, changes in the birefringent or the polarization properties of the articular cartilage were observed with OCT, suggesting collagen disorganization, an early indicator of osteoarthritis. Furthermore, this study supports the hypothesis that polarization-sensitive OCT may allow osteoarthritis to be diagnosed before cartilage thinning. This study illustrates that OCT, which can eventually be developed for use in offices or through an arthroscope, has considerable potential for assessing early osteoarthritic cartilage and monitoring therapeutic effects for cartilage repair with resolution in real time on a scale of micrometers.     

Trichoderma species--opportunistic, avirulent plant symbionts

Trichoderma spp. are free-living fungi that are common in soil and root ecosystems. Recent discoveries show that they are opportunistic, avirulent plant symbionts, as well as being parasites of other fungi. At least some strains establish robust and long-lasting colonizations of root surfaces and penetrate into the epidermis and a few cells below this level. They produce or release a variety of compounds that induce localized or systemic resistance responses, and this explains their lack of pathogenicity to plants. These root-microorganism associations cause substantial changes to the plant proteome and metabolism. Plants are protected from numerous classes of plant pathogen by responses that are similar to systemic acquired resistance and rhizobacteria-induced systemic resistance. Root colonization by Trichoderma spp. also frequently enhances root growth and development, crop productivity, resistance to abiotic stresses and the uptake and use of nutrients.     

Amino acid substitution at position 99 affects the rate of CRP subunit exchange

We investigated the characteristics of CRP having amino acid substitutions at position 99. Analysis of amino acid residue proximity to cAMP in molecular dynamics (MD) simulations of the CRP:(cAMP)(2) complex [García, A. E., and Harman, J. G. (1996) Protein Sci. 5, 62-71] showed repositioning of tyrosine 99 (Y99) to interact with the equatorial exocyclic oxygen atom of cAMP. To test the role of Y99 in cAMP-mediated CRP activation, Y99 was substituted with alanine (A) or phenylalanine (F). Cells that contained the WT or mutant forms of CRP induced beta-galactosidase in the presence of cAMP. Purified WT, Y99A, and Y99F CRP showed only a 3- to 4-fold difference in cAMP affinity. There were no apparent differences between the three forms of CRP in cAMP binding cooperativity, in CRP:(cAMP)(1) complex binding to lacP DNA, in the formation of CRP:cAMP:RNAP complexes at lacP, or in CRP efficacy in mediating lacP activity in vitro. The apo-form of Y99A CRP was more sensitive to protease than the apo-form of either WT CRP or Y99F CRP. Whereas the WT or Y99F CRP:(cAMP)(1) complexes were cleaved by protease at hinge-region peptide bonds, the Y99A CRP:(cAMP)(1) complex was cleaved at peptide bonds located at the subunit interface. The rates of subunit exchange for Y99A CRP, both in the apo-form and in a 1:1 complex with cAMP, were significantly greater than that measured for WT CRP. The results of this study show that tyrosine 99 contributes significant structural stability to the CRP dimer, specifically in stabilizing subunit association.     

Azathioprine plus prednisone in treatment of pemphigoid.

Twenty-five patients taking part in a controlled trial to compare azathioprine plus prednisone with prednisone alone in the treatment of pemphigoid were followed up for three years. Results showed that the addition of azathioprine 2.5 mg/kg body weight daily reduced the total maintenance dose of prednisone needed by about 45%, with no increase in serious side effects or mortality. The suggestion that azathioprine might increase the risk of disseminated malignancy in elderly patients was not supported. We conclude that in future trials the combination of azathioprine with prednisone should be used as the standard treatment for comparison.     

Autologous stromal vascular fraction cells: A tool for facilitating tolerance in rheumatic disease

Since the days of Medawar, the goal of therapeutic tolerogenesis has been a “Holy Grail” for immunologists. While knowledge of cellular and molecular mechanisms of this process has been increasing at an exponential rate, clinical progress has been minimal. To provide a mechanistic background of tolerogenesis, we overview common processes in the naturally occurring examples of: pregnancy, cancer, oral tolerance and anterior chamber associated immune deviation. The case is made that an easily accessible byproduct of plastic surgery, the adipose stromal vascular fraction, contains elements directly capable of promoting tolerogenesis such as T regulatory cells and inhibitory macrophages. The high content of mesenchymal and hematopoietic stem cells from this source provides the possibility of trophic/regenerative potential, which would augment tolerogenic processes by decreasing ongoing inflammation. We discuss the application of this autologous cell source in the context of rheumatoid arthritis, concluding with some practical examples of its applications.