Cell-based cancer gene therapy: breaking tolerance or inducing autoimmunity?

This review examines the mechanisms involved in anti-tumor immunity and how peptides present in many tumor types (tumor-associated antigens) are recognized by T cells from tumor-bearing cancer patients. Tumor-associated antigens are derived from proteins that are also expressed in normal cells. It is predicted that immune responses to such peptides will be compromised by self-tolerance or that stimulation of effective immune responses will be accompanied by autoimmunity. We also consider that the immunity induced against two autoantigens, which are highly conserved in vertebrates, involve qualitatively different mechanisms, such as the production of antibodies and cell-mediated immune responses. However, both pathways lead to tumor immunity and identical phenotypic manifestations of autoimmunity. Appropriate selection of the optimal tumor antigen is critical for the induction of an anti-tumor immune response. Thus, we stress that the methods for antigen presentation using dendritic cells play a critical role in the development of tumor vaccines, to break immune tolerance and induce a strong immune response against them. The viability and feasibility of expansion of canine dendritic cells from bone marrow and peripheral blood ex vivo for the treatment of spontaneous cancers in dogs is also discussed.     

Impact features on Stardust: implications for comet 81P/Wild 2 dust

Particles emanating from comet 81P/Wild 2 collided with the Stardust spacecraft at 6.1 kilometers per second, producing hypervelocity impact features on the collector surfaces that were returned to Earth. The morphologies of these surprisingly diverse features were created by particles varying from dense mineral grains to loosely bound, polymineralic aggregates ranging from tens of nanometers to hundreds of micrometers in size. The cumulative size distribution of Wild 2 dust is shallower than that of comet Halley, yet steeper than that of comet Grigg-Skjellerup.     

Detecting epistatic effects associated with cotton traits by a modified MDR approach

Genetic expression of a trait is complicated and it is usually associated with many genes including their interactions (epistasis) and genotype-by-environment interactions. Genetic mapping currently focuses primarily on additive models or marginal genetic effects due to the complexity of epistatic effects. Thus, there exists a need to appropriately identify favorable epistatic effects for important biological traits. Several multifactor dimensionality reduction (MDR) based methods are important resources to identify high-order gene–gene interactions. These methods are mainly focused on human genetic studies. Many traits in plant systems are not only quantitatively inherited but also are often measured in repeated field plots under multiple environments. In this study, we proposed a mixed model based MDR approach, which is suitable for inclusion of various fixed and random effects. This approach was used to analyze a cotton data set that included eight agronomic and fiber traits and 20 DNA markers. The results revealed high order epistatic effects were detected for most of these traits using this modified MDR approach.     

The technology path to deep greenhouse gas emissions cuts by 2050: the pivotal role of electricity

Several states and countries have adopted targets for deep reductions in greenhouse gas emissions by 2050, but there has been little physically realistic modeling of the energy and economic transformations required. We analyzed the infrastructure and technology path required to meet California's goal of an 80% reduction below 1990 levels, using detailed modeling of infrastructure stocks, resource constraints, and electricity system operability. We found that technically feasible levels of energy efficiency and decarbonized energy supply alone are not sufficient; widespread electrification of transportation and other sectors is required. Decarbonized electricity would become the dominant form of energy supply, posing challenges and opportunities for economic growth and climate policy. This transformation demands technologies that are not yet commercialized, as well as coordination of investment, technology development, and infrastructure deployment.     

Novel bivalent vectored vaccine for control of myxomatosis and rabbit haemorrhagic disease

A novel, recombinant myxoma virus-rabbit haemorrhagic disease virus (RHDV) vaccine has been developed for the prevention of myxomatosis and rabbit haemorrhagic disease (RHD). A number of laboratory studies are described illustrating the safety and efficacy of the vaccine following subcutaneous administration in laboratory rabbits from four weeks of age onwards. In these studies, both vaccinated and unvaccinated control rabbits were challenged using pathogenic strains of RHD and myxoma viruses, and 100 per cent of the vaccinated rabbits were protected against both myxomatosis and RHD.     

Influence of birth order,birth weight,colostrum and serum immunoglobulin G on neonatal piglet survival

Background

Intake of colostrum after birth is essential to stimulate intestinal growth and function, and to provide systemic immunological protection via absorption of Immunoglobulin G (IgG). The birth order and weight of 745 piglets (from 75 litters) were recorded during a one-week period of farrowing. Only pigs weighing greater than 0.68 kg birth weight were chosen for the trial. Sow colostrum was collected during parturition, and piglets were bled between 48 and 72 hours post-birth. Piglet serum IgG and colostral IgG concentrations were determined by radial immunodiffusion.

Results

Sow parity had a significant (P < 0.001) effect on sow colostral IgG concentration, being 5% higher in multiparous females. Sow colostral IgG concentration explained 6% and piglet birth order accounted for another 4% of the variation observed in piglet serum IgG concentration (P < 0.05); however, birth weight had no detectable effect. Piglet serum IgG concentration had both a linear (P < 0.05) and quadratic effect (P < 0.05) on % survival. Piglets with 1,000 mg/dl serum IgG or less (n=24) had a 67% survival; whereas, piglets with IgG concentrations between 2250 to 2500 mg/dl (n=247) had a 91% survival. Birth order had no detectable effect on survival, but birth weight had a positive linear effect (P < 0.05). Piglets weighing 0.9 kg (n = 107) at birth had a 68% survival rate, and those weighing 1.6 kg (n = 158) had an 89% survival.

Conclusion

We found that the combination of sow colostrum IgG concentration and birth order can account for 10% of the variation of piglet serum IgG concentration and that piglets with less than 1,000 mg/dl IgG serum concentration and weight of 0.9 kg at birth had low survival rate when compared to their larger siblings. The effective management of colostrum uptake in neonatal piglets in the first 24 hrs post-birth may potentially improve survival from birth to weaning.     

Fatal overdose after ingestion of a transdermal fentanyl patch in two non‐human primates

Case history and presentationTwo non-human primates (Macaca fascicularis), weight 3.5 kg, enrolled in an experimental protocol received a 25 μg hour^?1 transdermal fentanyl patch for postoperative analgesia. The following day both animals were clinically normal, but after a new induction of anaesthesia with ketamine, they developed severe and prolonged respiratory distress, profound coma and myosis.Management and follow-upAttempted reversal with naloxone was ineffective. After several hours of ventilation, both primates eventually died, 7 and 15 hours after ketamine injection, respectively. In both cases, the patch was discovered in the animal's cheek pouch. Subsequent fentanyl serum concentration measurements (8.29 and 14.80 μg L^?1) confirmed fentanyl overdose.ConclusionsThis report of two fatal intoxications in non-human primates secondary to ingestion of a transdermal fentanyl patch demonstrates that this method of analgesia is inappropriate for non-human primates, because of their tendency to chew almost anything they can reach.     

Theileria buffeli infection of a Michigan cow confirmed by small subunit ribosomal RNA gene analysis

Theileria buffeli, generally a benign parasite of cattle, has been reported in animals from Texas, Missouri and North Carolina. To date, there have been no reports of the parasite in cattle residing in northern portions of the US. An 8-year-old cow (Maine Anjou x Angus cross-bred) in Michigan presented with hemoglobinuria and a packed cell volume of 9. Blood films stained with Giemsa showed numerous intraerythrocytic parasites morphologically consistent with T. buffeli. The parasite was confirmed to be T. buffeli by SSU rRNA gene sequence analysis (SSU rRNA sequence, Type A). This represents the first report of this parasite in an animal in Michigan.