Physiologic assessment of blood glucose homeostasis via combined intravenous glucose and insulin testing in horses

OBJECTIVE: To characterize the physiologic response to i.v. bolus injection of glucose and insulin for development of a combined glucose-insulin test (CGIT) in horses. ANIMALS: 6 healthy mares and 1 mare each with pituitary adenoma and urolithiasis. PROCEDURE: Horses were given a CGIT (glucose, 150 mg/kg; insulin, 0.1 U/kg); results were compared with a singular i.v. glucose tolerance test (GTT; 150 mg/kg) and a singular i.v. insulin sensitivity test (IST; 0.1 U/kg). Healthy horses were also given a CGIT after receiving xylazine and undergoing stress. RESULTS: Physiologically, the CGIT resulted in a 2-phase curve with positive (hyperglycemic) and negative (hypoglycemic) portions; the positive phase came first (250% of baseline at 1 minute). The descending segment declined linearly to baseline by approximately 30 minutes and to a nadir at 58% of baseline by 75 minutes. After a 35-minute valley, a linear ascent to baseline began. Addition of insulin in the CGIT increased glucose utilization by approximately 4.5 times during the positive phase but not during the negative phase. The diseases' effects and experimental inhibition of insulin secretion with xylazine and stress were detectable by use of the 2 phases of the CGIT. Only a single positive phase resulted from the GTT and a single negative phase from the IST CONCLUSIONS AND CLINICAL RELEVANCE: The CGIT resulted in a consistent, well-defined glycemia profile, which can be disrupted experimentally or by a disease process. The CGIT has clinical potential because it provides integrated information and more information than either the singular GTT or IST.     

In vitro investigation of the effects of nonsteroidal anti-inflammatory drugs, prostaglandin E2, and prostaglandin F2alpha on contractile activity of the third compartment of the stomach of llamas

OBJECTIVE: To determine the in vitro effect of prostaglandin (PG) E2, PGF2alpha, and the nonsteroidal anti-inflammatory drugs (NSAIDs) indomethacin, ketoprofen, and nabumetone on the contractile strength of the circular smooth muscle layer of the third compartment of the stomach of llamas. SAMPLE POPULATION: Specimens of the third compartment obtained from 5 healthy adult llamas. PROCEDURE: Full-thickness tissue samples were collected from the third compartment immediately after euthanasia. Specimens were cut into strips oriented along the circular muscle layer and mounted in a tissue bath system. Incremental amounts of ketoprofen, nabumetone, indomethacin, PGE2, and PGF2alpha were added, and contractile strength (amplitude of contractions) was recorded. RESULTS: Generally, PGE2 reduced contractile strength of the circular smooth layer of the third compartment, whereas PGF2alpha, increased the strength of contractions. The activity of the NSAIDs was generally excitatory in a concentration-dependent manner, although significant changes were induced only by administration of indomethacin. CONCLUSIONS AND CLINICAL RELEVANCE: On isolated smooth muscle strips of the third compartment of llamas, exogenous PGE2 and PGF2alpha had a variable effect on contractile strength. Administration of the NSAIDs did not inhibit contractility and would not be likely to induce stasis of the third compartment in the absence of an underlying disease process.     

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.     

Extrachromosomal microDNAs and chromosomal microdeletions in normal tissues

We have identified tens of thousands of short extrachromosomal circular DNAs (microDNA) in mouse tissues as well as mouse and human cell lines. These microDNAs are 200 to 400 base pairs long, are derived from unique nonrepetitive sequence, and are enriched in the 5'-untranslated regions of genes, exons, and CpG islands. Chromosomal loci that are enriched sources of microDNA in the adult brain are somatically mosaic for microdeletions that appear to arise from the excision of microDNAs. Germline microdeletions identified by the "Thousand Genomes" project may also arise from the excision of microDNAs in the germline lineage. We have thus identified a previously unknown DNA entity in mammalian cells and provide evidence that their generation leaves behind deletions in different genomic loci.     

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.