Overcompensation of plants in response to herbivory and the by-product benefits of mutualism

Plants that overcompensate for herbivory are relatively healthier when damaged. In this mutualistic association, the herbivore benefits from the plant, and the plant benefits from the herbivore's actions. As long as the benefit to the plant outweighs the costs imposed by browsing herbivores, this interaction should remain stable. Many apparently parasitic associations can be mutually beneficial under some environmental conditions.     

Medicinal chemistry and therapeutic potential of CpG DNA

The observation that oligodeoxynucleotides containing CpG dinucleotides (CpG DNA) exhibit several immunological effects has led to their use as therapeutic agents and adjuvants for various diseases. Several CpG DNA drug candidates are currently being evaluated, either as monotherapies or as adjuvants (with vaccines, antibodies, antigens and allergens), in preclinical and clinical trials against cancers, viral and bacterial infections, allergies and asthma. Knowledge gained from studies of the medicinal chemistry of CpG DNA has provided a basis for designing a second generation of CpG DNA agents with desirable cytokine-inducing and potent immunomodulatory activity. This article reviews recent progress in understanding the effects of CpG DNA, the medicinal chemistry of CpG DNA, and its possible therapeutic applications.     

Multiparameter Analysis, including EMT Markers, on Negatively Enriched Blood Samples from Patients with Squamous Cell Carcinoma of the Head and Neck

Epithelial to mesenchymal transition (EMT) has been hypothesized as a mechanism by which cells change phenotype during carcinogenesis, as well as tumor metastasis. Whether EMT is involved in cancer metastasis has a specific, practical impact on the field of circulating tumor cells (CTCs). Since the generally accepted definition of a CTC includes the expression of epithelial surface markers, such as EpCAM, if a cancer cell loses its epithelial surface markers (which is suggested in EMT), it will not be separated and/or identified as a CTC. We have developed, and previously reported on the use of, a purely negative enrichment technology enriching for CTCs in the blood of squamous cell carcinoma of the head and neck (SCCHN). This methodology does not depend on the expression of surface epithelial markers. Using this technology, our initial data on SCCHN patient blood indicates that the presence of CTCs correlates with worse disease-free survival. Since our enrichment is not dependent on epithelial markers, we have initiated investigation of the presence of mesenchymal markers in these CTC cells to include analysis of: vimentin, epidermal growth factor receptor, N-cadherin, and CD44. With the aid of confocal microscopy, we have demonstrated not only presumed CTCs that express and/or contain: a nucleus, cytokeratins, vimentin, and either EGFR, CD44, or N-cadherin, but also cells that contain all of the aforementioned proteins except cytokeratins, suggesting that the cells have undergone the EMT process. We suggest that our negative depletion enrichment methodology provides a more objective approach in identifying and evaluating CTCs, as opposed to positive selection approaches, as it is not subjective to a selection bias and can be tailored to accommodate a variety of cytoplasmic and surface markers which can be evaluated to identify a multitude of phenotypic patterns within CTCs from individual patients, including so-called EMT as presented here.     

Alleviation of heavy metal stress in Spilanthes calva L. (antimalarial herb) by exogenous application of glutathione

To evaluate the role of exogenous application of a phytochelating agent glutathione in increasing resistance against different heavy metals stress, nodal explants excised from 28-day-old in vitro seedlings of Spilanthes calva L. were cultured on Murashige and Skoog’s medium supplemented with 10 μM benzyl adenine and five different concentrations (1, 5, 50, 100, or 200 mg/l) of four heavy metals: As₂O₃, CuSO₄, ZnSO₄, or Pb(NO₃)₂. Data were recorded for percent survival, shoot number, and shoot length after 28 d of heavy metal treatment. All four heavy metals severely inhibited growth and morphogenesis. Pb proved most inhibitory whereas Zn was least effective. Pb was further selected to study the reversal effect of glutathione on morphogenesis. The addition of different concentrations (1, 5, 10, or 25 mg/l) of glutathione to media containing the Pb resulted in a significant improvement in almost all growth parameters. Inclusion of glutathione at 10 mg/l was optimum for maximum reversal of the negative effects of heavy metals on morphogenesis.     

The effect of deleterious mutations and age on recombination in Drosophila melanogaster

At the population level, recombination mediates the efficiency with which selection can eliminate deleterious mutations. At the individual level, deleterious alleles may influence recombination, which would change the rate at which linkage disequilibrium is eroded and thereby alter the efficiency with which deleterious alleles are purged. Here, we test whether the presence of a deleterious allele on one autosome affects recombination on another autosome. We find that deleterious alleles not only alter the rate but also the pattern of recombination. However, there is little support that different deleterious alleles affect recombination in a consistent manner. Because we have detailed information on individual females across their lifetimes, we are able to examine how recombination patterns change with age and find that these patterns are also affected by the presence of deleterious alleles. The differences among genotypes or among age classes are large enough to add substantial noise to genetic mapping experiments that do not consider these sources of variation.     

Long-term in-vivo tumorigenic assessment of human culture-expanded adipose stromal/stem cells

After more than a decade of extensive experimentation, the promise of stem cells to revolutionize the field of medicine has negotiated their entry into clinical trial. Adipose tissue specifically holds potential as an attainable and abundant source of stem cells. Currently undergoing investigation are adipose stem cell (ASC) therapies for diabetes and critical limb ischemia, among others. In the enthusiastic pursuit of regenerative therapies, however, questions remain regarding ASC persistence and migration, and, importantly, their safety and potential for neoplasia. To date, assays of in vivo ASC activity have been limited by early end points. We hypothesized that with time, ASCs injected subcutaneously undergo removal by normal tissue turnover and homeostasis, and by the host's immune system. In this study, a high dose of culture expanded ASCs was formulated and implanted as multicellular aggregates into immunocompromised mice, which were maintained for over one year. Animals were monitored for toxicity, and surviving cells quantified at study endpoint. No difference in growth/weight or lifespan was found between cell-treated and vehicle treated animals, and no malignancies were detected in treated animals. Moreover, real-time PCR for a human specific sequence, ERV-3, detected no persistent ASCs. With the advent of clinical application, clarification of currently enigmatic stem cell properties has become imperative. Our study represents the longest duration determination of stem cell activity in vivo, and contributes strong evidence in support of the safety of adipose derived stem cell applications.