Integrating gene and protein expression data with genome-scale metabolic networks to infer functional pathways

This article has been made available through the Brunel Open Access Publishing Fund. Copyright @ 2013 Pey et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: The study of cellular metabolism in the context of high-throughput -omics data has allowed us to decipher novel mechanisms of importance in biotechnology and health. To continue with this progress, it is essential to efficiently integrate experimental data into metabolic modeling. Results: We present here an in-silico framework to infer relevant metabolic pathways for a particular phenotype under study based on its gene/protein expression data. This framework is based on the Carbon Flux Path (CFP) approach, a mixed-integer linear program that expands classical path finding techniques by considering additional biophysical constraints. In particular, the objective function of the CFP approach is amended to account for gene/protein expression data and influence obtained paths. This approach is termed integrative Carbon Flux Path (iCFP). We show that gene/protein expression data also influences the stoichiometric balancing of CFPs, which provides a more accurate picture of active metabolic pathways. This is illustrated in both a theoretical and real scenario. Finally, we apply this approach to find novel pathways relevant in the regulation of acetate overflow metabolism in Escherichia coli. As a result, several targets which could be relevant for better understanding of the phenomenon leading to impaired acetate overflow are proposed. Conclusions: A novel mathematical framework that determines functional pathways based on gene/protein expression data is presented and validated. We show that our approach is able to provide new insights into complex biological scenarios such as acetate overflow in Escherichia coli.Basque Governmen

Kinetic parameters for nutrient enhanced crude oil biodegradation in intertidal marine sediments

Availability of inorganic nutrients, particularly nitrogen and phosphorous, is often a primary control on crude oil hydrocarbon degradation in marine systems. Many studies have empirically determined optimum levels of inorganic N and P for stimulation of hydrocarbon degradation. Nevertheless, there is a paucity of information on fundamental kinetic parameters for nutrient enhanced crude oil biodegradation that can be used to model the fate of crude oil in bioremediation programmes that use inorganic nutrient addition to stimulate oil biodegradation. Here we report fundamental kinetic parameters (Ks and qmax) for nitrate-and phosphate-stimulated crude oil biodegradation under nutrient limited conditions and with respect to crude oil, under conditions where N and P are not limiting. In the marine sediments studied, crude oil degradation was limited by both N and P availability. In sediments treated with 12.5 mg/g of oil but with no addition of N and P, hydrocarbon degradation rates, assessed on the basis of CO2 production, were 1.10 ± 0.03 μmol CO2/g wet sediment/day which were comparable to rates of CO2 production in sediments to which no oil was added (1.05 ± 0.27 μmol CO2/g wet sediment/day). When inorganic nitrogen was added alone maximum rates of CO2 production measured were 4.25 ± 0.91 μmol CO2/g wet sediment/day. However, when the same levels of inorganic nitrogen were added in the presence of 0.5% P w/w of oil (1.6 μmol P/g wet sediment) maximum rates of measured CO2 production increased more than four-fold to 18.40 ± 1.04 μmol CO2/g wet sediment/day. Ks and qmax estimates for inorganic N (in the form of sodium nitrate) when P was not limiting were 1.99 ± 0.86 μmol/g wet sediment and 16.16 ± 1.28 μmol CO2/g wet sediment/day respectively. The corresponding values for P were 63 ± 95 nmol/g wet sediment and 12.05 ± 1.31 μmol CO2/g wet sediment/day. The qmax values with respect to N and P were not significantly different (P < 0.05). When N and P were not limiting Ks and qmax for crude oil were 4.52 ± 1.51 mg oil/g wet sediment and 16.89 ± 1.25 μmol CO2/g wet sediment/day. At concentrations of inorganic N above 45 μmol/g wet sediment inhibition of CO2 production from hydrocarbon degradation was evident. Analysis of bacterial 16S rRNA genes indicated that Alcanivorax spp. were selected in these marine sediments with increasing inorganic nutrient concentration, whereas Cycloclasticus spp. were more prevalent at lower inorganic nutrient concentrations. These data suggest that simple empirical estimates of the proportion of nutrients added relative to crude oil concentrations may not be sufficient to guarantee successful crude oil bioremediation in oxic beach sediments. The data we present also help define the maximum rates and hence timescales required for bioremediation of beach sediments

A note on "symmetric" vielbeins in bimetric, massive, perturbative and non perturbative gravities

We consider a manifold endowed with two different vielbeins $E^{A}{}_{\mu}$ and $L^{A}{}_{\mu}$ corresponding to two different metrics $g_{\mu\nu}$ and $f_{\mu\nu}$. Such a situation arises generically in bimetric or massive gravity (including the recently discussed version of de Rham, Gabadadze and Tolley), as well as in perturbative quantum gravity where one vielbein parametrizes the background space-time and the other the dynamical degrees of freedom. We determine the conditions under which the relation $g^{\mu\nu} E^{A}{}_{\mu} L^{B}{}_{\nu} = g^{\mu\nu} E^{B}{}_{\mu} L^{A}{}_{\nu}$ can be imposed (or the "Deser-van Nieuwenhuizen" gauge chosen). We clarify and correct various statements which have been made about this issue.Comment: 20 pages. Section 7, prop. 6 and 7. added. Some results made more precis

Consumer acceptance of yellow, provitamin A-biofortified maize in KwaZulu-Natal

Objectives: To assess the acceptance of popular maize food products (phutu, thin porridge and samp), prepared with yellow, provitamin A-biofortified maize varieties, in 212 subjects between the ages of three and 55 years, from rural KwaZulu-Natal.Design: A cross-sectional study.Method: Preschool, primary school and secondary school subjects were randomly selected from two primary schools and one secondary school, respectively, while adult subjects constituted a convenience sample. Pre- and primary school children completed a paired preference test. Secondary school and adult subjects completed a five-point facial hedonic and a preference ranking test. Focus group discussions were conducted using adult subjects.Results: Preschool children preferred yellow maize to white maize food products: phutu (81% vs. 19%; p-value &lt; 0.001), thin porridge (75% vs. 25%; p-value &lt; 0.001) and samp (73% vs. 27%; p-value &lt; 0.001). There was no statistically significant difference in preference for white and yellow maize by primary school children. Secondary school and adult subjects preferred white maize to yellow maize. Focus group discussions confirmed the preference for white maize by the adults.Conclusion: The study findings suggest that yellow, provitamin A-biofortified maize has the potential to succeed as a new strategy of dealing with the serious problem of vitamin A deficiency, especially among children of preschool age. However, in older groups, this strategy is unlikely to be successful, unless other strategies are implemented, including intensive nutrition education programmes on the nutritional benefits of the maize, targeting the market price at which yellow maize is sold, increasing its availability in local grocery stores, and improving its sensory properties through breeding.Keywords: yellow maize, provitamin A, vitamin A deficiency, consumer acceptanc

Acceptance of a ready-to-use supplementary food by stable HIV-treated and HIV and tuberculosis (co-infected)-treated patients

Objectives: The objective of the study was to determine consumer  acceptance and perceptions of a ready-to-use supplementary food (RUSF)by subjects treated for human immunodeficiency virus (HIV) and HIV and tuberculosis (co-infected subjects).Design: A cross-sectional study was conducted.Subjects: One hundred and thirty-nine stable HIV-treated and HIV and tuberculosis (co-infected)-treated patients participated in the study. Sixty-eight healthy subjects served as the control group.Setting: The setting was Northdale Hospital and Grey’s Hospital in  Pietermaritzburg, KwaZulu-Natal.Outcome measures: Acceptance of the RUSF was assessed using a five-point facial hedonic scale by stable HIV-treated and HIV and tuberculosis (co-infected)-treated patients (n = 139) from Northdale Hospital and Grey’s Hospital in Pietermaritzburg, KwaZulu-Natal. Perceptions of the RUSF were determined through focus group discussions in which HIV-treated and HIV and tuberculosis (co-infected)-treated patients (n = 43) participated.Results: The overall acceptance of the RUSF was significantly associated with the health status of the subjects (p-value &lt; 0.05). Overall, the product was liked by more than 90% of the HIV-treated and HIV and tuberculosis (co-infected)-treated individuals compared to 85% of the control group. More than 90% of the HIV-treated and HIV and tuberculosis   (co-infected)-treated individuals liked the taste, compared to 87% of the control group. The colour and mouth feel were rated to be “good” by more than 80% of the HIV-treated and HIV and tuberculosis (coinfected)-treated group, compared to approximately 70% of the healthy group. Focus group discussions revealed that the subjects perceived the mouth feel of the RUSF to be “rough”, and that as a health supplement, the RUSF should be provided free of charge, or at a reasonable cost, at public health centres.Conclusion: The RUSF was found to be highly acceptable to stable   HIV-treated and HIV and tuberculosis (co-infected)-treated subjects, although concern was raised about the mouth feel

On the Concept of a Notational Variant

In the study of modal and nonclassical logics, translations have frequently been employed as a way of measuring the inferential capabilities of a logic. It is sometimes claimed that two logics are “notational variants” if they are translationally equivalent. However, we will show that this cannot be quite right, since first-order logic and propositional logic are translationally equivalent. Others have claimed that for two logics to be notational variants, they must at least be compositionally intertranslatable. The definition of compositionality these accounts use, however, is too strong, as the standard translation from modal logic to first-order logic is not compositional in this sense. In light of this, we will explore a weaker version of this notion that we will call schematicity and show that there is no schematic translation either from first-order logic to propositional logic or from intuitionistic logic to classical logic

Pacing Profiles in Competitive Track Races: Regulation of Exercise Intensity is related to Cognitive Ability

Pacing has been defined as the goal-directed regulation of exercise intensity over an exercise bout, in which athletes need to decide how and when to invest their energy. The purpose of this study was to explore if the regulation of exercise intensity during competitive track races is different between runners with and without intellectual impairment, which is characterized by significant limitations in intellectual functioning (IQ ≤ 75) and adaptive behavioral deficits, diagnosed before the age of 18. The samples included elite runners with intellectual impairment (N = 36) and a comparison group of world class runners without impairment (N = 39), of which 47 were 400 m runners (all male) and 28 were 1500 m-runners (15 male and 13 female). Pacing was analyzed by means of 100 m split times (for 400 m races) and 200 m split times (for 1500 m races). Based on the split times, the average velocity was calculated for four segments of the races. Velocity fluctuations were defined as the differences in velocity between consecutive race segments. A mixed model ANOVA revealed significant differences in pacing profiles between runners with and without intellectual impairment (p < 0.05). Maximal velocity of elite 400 m runners with intellectual impairment in the first race segment (7.9 ± 0.3 m/s) was well below the top-velocity reached by world level 400 m runners without intellectual impairment (8.9 ± 0.2 m/s), and their overall pace was slower (F = 120.7, p < 0.05). In addition, both groups followed a different pacing profile and inter-individual differences in pacing profiles were larger, with differences most pronounced for 1500 m races. Whereas, male 1500 m-runners without intellectual impairment reached a high velocity in the first 100 m (7.2 ± 0.1 m/s), slowly decelerated in the second race segment (−0.6 ± 0.1 m/s), and finished with an end sprint (+0.9 ± 0.1 m/s); the 1500 m runners with intellectual impairment started slower (6.1 ± 0.3 m/s), accelerated in the second segment (+0.2 ± 0.7 m/s), and then slowly decreased until the finish (F = 6.8, p < 0.05). Our findings support the hypothesis that runners with intellectual impairment have difficulties to efficiently self-regulate their exercise intensity. Their limited cognitive resources may constrain the successful integration of appropriate pacing strategies during competitive races