Mechanisms and development of self–other distinction in dyads and groups

This opinion piece offers a commentary on the four papers that address the theme of the development of self and other understanding with a view to highlighting the important contribution of developmental research to understanding of mechanisms of social cognition. We discuss potential mechanisms linking self–other distinction and empathy, implications for grouping motor, affective and cognitive domains under a single mechanism, applications of these accounts for joint action and finally consider self–other distinction in group versus dyadic settings.     

Development of an Automated and Sensitive Microfluidic Device for Capturing and Characterizing Circulating Tumor Cells (CTCs) from Clinical Blood Samples

Current analysis of circulating tumor cells (CTCs) is hindered by sub-optimal sensitivity and specificity of devices or assays as well as lack of capability of characterization of CTCs with clinical biomarkers. Here, we validate a novel technology to enrich and characterize CTCs from blood samples of patients with metastatic breast, prostate and colorectal cancers using a microfluidic chip which is processed by using an automated staining and scanning system from sample preparation to image processing. The Celsee system allowed for the detection of CTCs with apparent high sensitivity and specificity (94% sensitivity and 100% specificity). Moreover, the system facilitated rapid capture of CTCs from blood samples and also allowed for downstream characterization of the captured cells by immunohistochemistry, DNA and mRNA fluorescence in-situ hybridization (FISH). In a subset of patients with prostate cancer we compared the technology with a FDA-approved CTC device, CellSearch and found a higher degree of sensitivity with the Celsee instrument. In conclusion, the integrated Celsee system represents a promising CTC technology for enumeration and molecular characterization.     

Th17 Pathway As a Target for Multipotent Stromal Cell Therapy in Dogs: Implications for Translational Research

Detrimental Th17 driven inflammatory and autoimmune disease such as Crohn’s disease, graft versus host disease and multiple sclerosis remain a significant cause of morbidity and mortality worldwide. Multipotent stromal/stem cell (MSC) inhibit Th17 polarization and activation in vitro and in rodent models. As such, MSC based therapeutic approaches are being investigated as novel therapeutic approaches to treat Th17 driven diseases in humans. The significance of naturally occurring diseases in dogs is increasingly recognized as a realistic platform to conduct pre-clinical testing of novel therapeutics. Full characterization of Th17 cells in dogs has not been completed. We have developed and validated a flow-cytometric method to detect Th17 cells in canine blood. We further demonstrate that Th17 and other IL17 producing cells are present in tissues of dogs with naturally occurring chronic inflammatory diseases. Finally, we have determined the kinetics of a canine specific Th17 polarization in vitro and demonstrate that canine MSC inhibit Th17 polarization in vitro, in a PGE₂ independent mechanism. Our findings provide fundamental research tools and suggest that naturally occurring diseases in dogs, such as inflammatory bowel disease, may be harnessed to translate novel MSC based therapeutic strategies that target the Th17 pathway.     

Models for Trypanosoma evansi (surra), its control and economic impact on small-hold livestock owners in the Philippines

Simple demographic and infectious disease models of buffaloes and other domestic hosts for animal trypanosomosis (surra) caused by Trypanosoma evansi were developed. The animal models contained deterministic and stochastic elements and were linked to simulate the benefit of control regimes for surra in village domestic animal populations in Mindanao, Philippines. The impact of the disease on host fertility and mortality were key factors in determining the economic losses and net-benefit from the control regimes. If using a high (99%) efficacy drug in surra-moderate to high risk areas, then treating all animals twice each year yielded low prevalence in 2 years; targeted treatment of clinically sick animals, constantly monitored (monthly), required 75% fewer treatments but took longer to reach a low prevalence than treating all animals twice each year. At high drug efficacy both of these treatment strategies increased the benefit over untreated animals by 81%. If drug efficacy declined then the benefit obtained from twice yearly treatment of all animals declined rapidly compared with regular monitoring and targeting treatment to clinically sick animals. The current control regimen applied in the Philippines of annual sero-testing for surra and only treating sero-positive animals provided the lowest net-benefit of all the control options simulated and would not be regarded as effective control. The total net-benefit from effective surra control for a typical village in a moderate/high risk area was 7.9 million pesos per annum (US $158,000). The value added to buffaloes, cattle, horses, goats/sheep and pigs as a result of this control was US $88, $84, $151, $7, $114 per animal/year, respectively.     

Genetic structure of a wide-spectrum chicken gene pool

The genetic structure of 65 chicken populations was studied using 29 simple sequence repeat loci. Six main clusters which corresponded to geographical origins and histories were identified: Brown Egg Layers; predominantly Broilers; native Chinese breeds or breeds with recent Asian origin; predominantly breeds of European derivation; a small cluster containing populations with no common history and populations that had breeding history with White Leghorn. Another group of populations that shared their genome with several clusters was defined as 'Multi-clusters'. Gallus gallus gallus (Multi-clusters), one of the subspecies of the Red Jungle Fowl, which was previously suggested to be one of the ancestors of the domesticated chicken, has almost no shared loci with European and White Egg layer populations. In a further sub-clustering of the populations, discrimination between all the 65 populations was possible, and relationships between each were suggested. The genetic variation between populations was found to account for about 34% of the total genetic variation, 11% of the variation being between clusters and 23% being between populations within clusters. The suggested clusters may assist in future studies of genetic aspects of the chicken gene pool.     

Do foliar endophytes affect grass litter decomposition? A microcosm approach using Lolium multiflorum

Symbiotic infection with fungal endophytes has been shown to decrease herbivory in several temperate grasses. We tested the hypothesis that foliar endophytes of grasses may also affect below-ground processes upon their host death, by altering the litter quality for detritivores or the microenvironment for decomposition. Microcosm–litterbag experiments were used to assess decay rates for litter produced by endophyte ( Neotyphodium sp.) infected vs uninfected Lolium multiflorum plants, and to examine endophyte-mediated effects of prior site occupants on current litter decomposition. We found that litter from endophyte-infected L. multiflorum decomposed more slowly than litter from endophyte-free conspecifics and from a naturally uninfected grass, Bromus unioloides . Furthermore, the endophyte–grass association modified the decomposition environment, so that B. unioloides litter decomposed faster when placed underneath a thick layer of endophyte-free L. multiflorum litter. Litter decay rates increased with the amount of root debris remaining in situ from the previous season, but were not affected by the infection status of prior site occupants. The lower decomposability of litter from infected L. multiflorum plants persisted across a range of microenvironments, as determined by different amounts of above-ground litter and soil moisture conditions. Endophyte infection tended to reduce the N content of decaying litter; however, litter N and C/N ratio mainly accounted for interspecific differences in decomposition. Our results imply that fungal endophytes not only can affect herbivory food chains, but also soil organisms and the ecosystem processes they regulate. This study suggests a novel role for symbiotic foliar endophytes in linking above-ground and below-ground sub-systems.     

MiR-101 and miR-144 Regulate the Expression of the CFTR Chloride Channel in the Lung

The Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is a chloride channel that plays a critical role in the lung by maintaining fluid homeostasis. Absence or malfunction of CFTR leads to Cystic Fibrosis, a disease characterized by chronic infection and inflammation. We recently reported that air pollutants such as cigarette smoke and cadmium negatively regulate the expression of CFTR by affecting several steps in the biogenesis of CFTR protein. MicroRNAs (miRNAs) have recently received a great deal of attention as both biomarkers and therapeutics due to their ability to regulate multiple genes. Here, we show that cigarette smoke and cadmium up-regulate the expression of two miRNAs (miR-101 and miR-144) that are predicted to target CFTR in human bronchial epithelial cells. When premature miR-101 and miR-144 were transfected in human airway epithelial cells, they directly targeted the CFTR 3′UTR and suppressed the expression of the CFTR protein. Since miR-101 was highly up-regulated by cigarette smoke in vitro, we investigated whether such increase also occurred in vivo. Mice exposed to cigarette smoke for 4 weeks demonstrated an up-regulation of miR-101 and suppression of CFTR protein in their lungs. Finally, we show that miR-101 is highly expressed in lung samples from patients with severe chronic obstructive pulmonary disease (COPD) when compared to control patients. Taken together, these results suggest that chronic cigarette smoking up-regulates miR-101 and that this miRNA could contribute to suppression of CFTR in the lungs of COPD patients.