Comprehensive multiplexed protein quantitation delineates eosinophilic and neutrophilic experimental asthma

Background: Improvements in asthma diagnosis and management require deeper understanding of the heterogeneity of the complex airway inflammation. We hypothesise that differences in the two major inflammatory phenotypes of asthma; eosinophilic and neutrophilic asthma, will be reflected in the lung protein expression profile of murine asthma models and can be delineated using proteomics of bronchoalveolar lavage (BAL). Methods: BAL from mice challenged with ovalbumin (OVA/OVA) alone (standard model of asthma, here considered eosinophilic) or OVA in combination with endotoxin (OVA/LPS, model of neutrophilic asthma) was analysed using liquid chromatography coupled to high resolution mass spectrometry, and compared with steroid-treated animals and healthy controls. In addition, conventional inflammatory markers were analysed using multiplexed ELISA (Bio-Plex T assay). Multivariate statistics was performed on integrative proteomic fingerprints using principal component analysis. Proteomic data were complemented with lung mechanics and BAL cell counts. Results: Several of the analysed proteins displayed significant differences between the controls and either or both of the two models reflecting eosinophilic and neutrophilic asthma. Most of the proteins found with mass spectrometry analysis displayed a considerable increase in neutrophilic asthma compared with the other groups. Conversely, the larger number of the inflammatory markers analysed with Bio-Plex T analysis were found to be increased in the eosinophilic model. In addition, major inflammation markers were correlated to peripheral airway closure, while commonly used asthma biomarkers only reflect central inflammation. Conclusion: Our data suggest that the commercial markers we are currently relying on to diagnose asthma subtypes are not giving us comprehensive or specific enough information. The analysed protein profiles allowed to discriminate the two models and may add useful information for characterization of different asthma phenotypes

Genetics against race: Science, politics and affirmative action in Brazil

This article analyses interrelations between genetic ancestry research, political conflict and social identity. It focuses on the debate on race-based affirmative action policies, which have been implemented in Brazil since the turn of the century. Genetic evidence of high levels of admixture in the Brazilian population has become a key element of arguments that question the validity of the category of race for the development of public policies. In response, members of Brazil’s black movement have dismissed the relevance of genetics by arguing, first, that in Brazil race functions as a social – rather than a biological – category, and, second, that racial classification and discrimination in this country are based on appearance, rather than on genotype. This article highlights the importance of power relations and political interests in shaping public engagements with genetic research and their social consequences

Feeding high-moisture corn grain silage to broilers fed alternative diets and maintained at different environmental temperatures

The effects of the dietary substitution of dry corn by high-moisture corn grain silage (HMCGS) were evaluated on the performance, nutrient digestibility and serum biochemical parameters of broilers reared in an alternative production system and submitted to different environmental temperatures. A total of 288 one-day-old male Cobb chicks were distributed according to a randomized block design in a 3x4 factorial arrangement: three environmental temperatures (hot, thermoneutral or cold) and four levels of HMCGS in substitution of dry corn (0%, 20%, 40% or 60%). The acid analysis showed that the evaluated HMCGS contained average percentage values of ethanol, lactic acid, and acetic acid (expressed in 100% of dry matter) of 0.7690, 2.7320 and 0.0249%, respectively. Propionic and butyric acids were not detected. Dry corn and HMCGS presented pH values of 5.8 and 3.3, respectively. The inclusion of HMCGS reduced dietary pH, as shown by the values of 5.7, 5.4, 5.1 and 4.8 recorded for the diets containing 0%, 20%, 40% and 60% of HMCGS, respectively. There was no significant interaction between diets and environmental temperature. HMCGS may replace up to 40% dry corn in broiler diets when performance, triglyceride levels, and HDL-cholesterol ratio is considered, and up to 60% when nutrient digestibility is evaluated. High environmental temperature impairs broiler performance, nutrient digestibility, and serum biochemistry, demonstrating the influence of environmental temperature on broiler metabolism and performance.Fundação para o Desenvolvimento da UNESP (FUNDUNESP)Sao Paulo State Univ UNESP Dracena, Anim Sci Sch, Sao Paulo, BrazilSao Paulo State Univ UNESP Botucatu, Sch Vet Med &Anim Sci, Dept Anim Breeding &Nutr, Sao Paulo, BrazilSao Paulo State Univ UNESP Botucatu, Inst Biosci, Dept Physiol, Sao Paulo, BrazilUniv Sao Paulo USP Pirassununga, Sch Vet Med &Anim Sci, Dept Anim Nutr &Prod, Sao Paulo, BrazilState Univ Maringa UEM Maringa, Dept Anim Sci, Sao Paulo, BrazilSao Paulo State Univ UNESP Dracena, Anim Sci Sch, Sao Paulo, BrazilSao Paulo State Univ UNESP Botucatu, Sch Vet Med &Anim Sci, Dept Anim Breeding &Nutr, Sao Paulo, BrazilSao Paulo State Univ UNESP Botucatu, Inst Biosci, Dept Physiol, Sao Paulo, Brazi

Animal models of asthma

Animal models of asthma are a tool that allows studies to be conducted in the setting of an intact immune and respiratory system. These models have highlighted the importance of T-helper type 2 driven allergic responses in the progression of asthma and have been useful in the identification of potential drug targets for interventions involving allergic pathways. However, a number of drugs that have been shown to have some efficacy in animal models of asthma have shown little clinical benefit in human asthmatics. This may be due to a number of factors including the species of animal chosen and the methods used to induce an asthmatic phenotype in animals that do not normally develop a disease that could be characterized as asthma. The range of animal models available is vast, with the most popular models being rodents (inbred mice and rats) and guinea-pigs, which have the benefit of being easy to handle and being relatively cost effective compared with other models that are available. The recent advances in transgenic technology and the development of species-specific probes, particularly in mice, have allowed detailed mechanistic studies to be conducted. Despite these advances in technology, there are a number of issues with current animal models of asthma that must be recognized including the disparity in immunology and anatomy between these species and humans, the requirement for adjuvant during senitization in most models, the acute nature of the allergic response that is induced and the use of adult animals as the primary disease model. Some larger animal models using sheep and dogs have been developed that may address some of these issues but they also have different biology from humans in many ways and are extremely costly, with very few probes available for characterizing allergic responses in the airway in these species. As research in this area continues to expand, the relative merits and limitations of each model must be defined and understood in order to evaluate the information that is obtained from these models and to extrapolate these findings to humans so that effective drug therapies can be developed. Despite these issues, animal models have been, and will continue to be, vital in understanding the mechanisms that are involved in the development and progression of asthma