Metabolomics, lipidomics and proteomics profiling of myoblasts infected with Trypanosoma cruzi after treatment with different drugs against Chagas disease.

INTRODUCTION: Chagas disease, the most important parasitic infection in Latin America, is caused by the intracellular protozoan Trypanosoma cruzi. To treat this disease, only two nitroheterocyclic compounds with toxic side effects exist and frequent treatment failures are reported. Hence there is an urgent need to develop new drugs. Recently, metabolomics has become an efficient and cost-effective strategy for dissecting drug mode of action, which has been applied to bacteria as well as parasites, such as different Trypanosome species and forms. OBJECTIVES: We assessed if the metabolomics approach can be applied to study drug action of the intracellular amastigote form of T. cruzi in a parasite-host cell system. METHODS: We applied a metabolic fingerprinting approach (DI-MS and NMR) to evaluate metabolic changes induced by six different (candidate) drugs in a parasite-host cell system. In a second part of our study, we analyzed the impact of two drugs on polar metabolites, lipid and proteins to evaluate if affected pathways can be identified. RESULTS: Metabolic signatures, obtained by the fingerprinting approach, resulted in three different clusters. Two can be explained by already known of mode actions, whereas the three experimental drugs formed a separate cluster. Significant changes induced by drug action were observed in all the three metabolic fractions (polar metabolites, lipids and proteins). We identified a general impact on the TCA cycle, but no specific pathways could be attributed to drug action, which might be caused by a high percentage of common metabolome between a eukaryotic host cell and a eukaryotic parasite. Additionally, ion suppression effects due to differences in abundance between host cells and parasites may have occurred. CONCLUSION: We validated the metabolic fingerprinting approach to a complex host-cell parasite system. This technique can potentially be applied in the early stage of drug discovery and could help to prioritize early leads or reconfirmed hits for further development

Validation of food store environment secondary data source and the role of neighborhood deprivation in Appalachia, Kentucky

Background Based on the need for better measurement of the retail food environment in rural settings and to examine how deprivation may be unique in rural settings, the aims of this study were: 1) to validate one commercially available data source with direct field observations of food retailers; and 2) to examine the association between modified neighborhood deprivation and the modified retail food environment score (mRFEI). Methods Secondary data were obtained from a commercial database, InfoUSA in 2011, on all retail food outlets for each census tract. In 2011, direct observation identifying all listed food retailers was conducted in 14 counties in Kentucky. Sensitivity and positive predictive values (PPV) were compared. Neighborhood deprivation index was derived from American Community Survey data. Multinomial regression was used to examine associations between neighborhood deprivation and the mRFEI score (indicator of retailers selling healthy foods such as low-fat foods and fruits and vegetables relative to retailers selling more energy dense foods). Results The sensitivity of the commercial database was high for traditional food retailers (grocery stores, supermarkets, convenience stores), with a range of 0.96-1.00, but lower for non-traditional food retailers; dollar stores (0.20) and Farmer’s Markets (0.50). For traditional food outlets, the PPV for smaller non-chain grocery stores was 38%, and large chain supermarkets was 87%. Compared to those with no stores in their neighborhoods, those with a supercenter [OR 0.50 (95% CI 0.27. 0.97)] or convenience store [OR 0.67 (95% CI 0.51, 0.89)] in their neighborhood have lower odds of living in a low deprivation neighborhood relative to a high deprivation neighborhood. Conclusion The secondary commercial database used in this study was insufficient to characterize the rural retail food environment. Our findings suggest that neighborhoods with high neighborhood deprivation are associated with having certain store types that may promote less healthy food options

Significance of Input Correlations in Striatal Function

The striatum is the main input station of the basal ganglia and is strongly associated with motor and cognitive functions. Anatomical evidence suggests that individual striatal neurons are unlikely to share their inputs from the cortex. Using a biologically realistic large-scale network model of striatum and cortico-striatal projections, we provide a functional interpretation of the special anatomical structure of these projections. Specifically, we show that weak pairwise correlation within the pool of inputs to individual striatal neurons enhances the saliency of signal representation in the striatum. By contrast, correlations among the input pools of different striatal neurons render the signal representation less distinct from background activity. We suggest that for the network architecture of the striatum, there is a preferred cortico-striatal input configuration for optimal signal representation. It is further enhanced by the low-rate asynchronous background activity in striatum, supported by the balance between feedforward and feedback inhibitions in the striatal network. Thus, an appropriate combination of rates and correlations in the striatal input sets the stage for action selection presumably implemented in the basal ganglia

Measures of the Consumer Food Store Environment: A Systematic Review of the Evidence 2000–2011

Description of the consumer food environment has proliferated in publication. However, there has been a lack of systematic reviews focusing on how the consumer food environment is associated with the following: (1) neighborhood characteristics; (2) food prices; (3) dietary patterns; and (4) weight status. We conducted a systematic review of primary, quantitative, observational studies, published in English that conducted an audit of the consumer food environment. The literature search included electronic, hand searches, and peer-reviewed from 2000 to 2011. Fifty six papers met the inclusion criteria. Six studies reported stores in low income neighborhoods or high minority neighborhoods had less availability of healthy food. While, four studies found there was no difference in availability between neighborhoods. The results were also inconsistent for differences in food prices, dietary patterns, and weight status. This systematic review uncovered several key findings. (1) Systematic measurement of determining availability of food within stores and store types is needed; (2) Context is relevant for understanding the complexities of the consumer food environment; (3) Interventions and longitudinal studies addressing purchasing habits, diet, and obesity outcomes are needed; and (4) Influences of price and marketing that may be linked with why people purchase certain items