MetaboTools: A comprehensive toolbox for analysis of genome-scale metabolic models

Metabolomic data sets provide a direct read-out of cellular phenotypes and are increasingly generated to study biological questions. Our previous work revealed the potential of analyzing extracellular metabolomic data in the context of the metabolic model using constraint-based modeling. Through this work, which consists of a protocol, a toolbox, and tutorials of two use cases, we make our methods available to the broader scientific community. The protocol describes, in a step-wise manner, the workflow of data integration and computational analysis. The MetaboTools comprise the Matlab code required to complete the workflow described in the protocol. Tutorials explain the computational steps for integration of two different data sets and demonstrate a comprehensive set of methods for the computational analysis of metabolic models and stratification thereof into different phenotypes. The presented workflow supports integrative analysis of multiple omics data sets. Importantly, all analysis tools can be applied to metabolic models without performing the entire workflow. Taken together, this protocol constitutes a comprehensive guide to the intra-model analysis of extracellular metabolomic data and a resource offering a broad set of computational analysis tools for a wide biomedical and non-biomedical research community

The Impact Of Continuous Prenatal And Early Postpartum Maternal Vitamin D Supplementation On The Vitamin D Status Of Exclusively Breastfed Infants

ABSTRACT In the United States, at least 50% of breastfeeding mothers are vitamin D deficient, increasing risk for vitamin D deficiency in exclusively breastfed infants. A gap in knowledge exists regarding best practices in maternal vitamin D supplementation during pregnancy and lactation that will yield adequate infant vitamin D levels. The objective of this study was to identify the combined effect of maternal prenatal and postnatal vitamin D supplementation on vitamin D transfer to exclusively breastfed infants. Additionally, due to the immune modulating effects of vitamin D, maternal pro- and anti-inflammatory cytokines were measured across pregnancy and the postpartum. A double-blind, randomized controlled trial design was used. A total of 16 pregnant women were enrolled in the study at 24-28 weeks gestation. The control group (N= 6) received a prenatal vitamin containing vitamin D 400 IU daily plus a placebo void of vitamin D. The experimental group (N=7) received the same prenatal vitamin plus a capsule containing 3400 IU vitamin D, for a total of 3800 IU daily. Participants continued their assigned supplements through 4-6 weeks of lactation. Pertinent pregnancy, delivery, and postnatal health data were collected on maternal and infant participants. Serum levels of 25-hydroxyvitamin D were measured in maternal participants at enrollment and in both maternal and infant participants at delivery and after 4-6 weeks of lactation. Maternal plasma TNF-alpha, IL-6, and IL-10 were measured at enrollment, delivery and 4-6 weeks of lactation. There was a significant effect of maternal vitamin D supplementation on maternal 25-hydroxyvitamin D at delivery (p=0.044) and at 4-6 weeks of lactation (p=0.002). A significant difference in the infant participant groups at delivery was also found (p=0.017), however this was not significant at 4-6 weeks of lactation (p=0.256). Controlling for maternal baseline using repeated measures techniques, the overall effect of maternal vitamin D supplementation on infant 25-hydroxyvitamin D approached significance (p=0.065). There was no impact of vitamin D supplementation on maternal cytokine production. This study adds novel information regarding the impact of continuous prenatal to postpartum maternal vitamin D supplementation on the vitamin D status of exclusively breastfed infants

Dewetting of thin films on heterogeneous substrates: Pinning vs. coarsening

We study a model for a thin liquid film dewetting from a periodic heterogeneous substrate (template). The amplitude and periodicity of a striped template heterogeneity necessary to obtain a stable periodic stripe pattern, i.e. pinning, are computed. This requires a stabilization of the longitudinal and transversal modes driving the typical coarsening dynamics during dewetting of a thin film on a homogeneous substrate. If the heterogeneity has a larger spatial period than the critical dewetting mode, weak heterogeneities are sufficient for pinning. A large region of coexistence between coarsening dynamics and pinning is found.Comment: 4 pages, 4 figure

Bifurcation analysis of the behavior of partially wetting liquids on a rotating cylinder

We discuss the behavior of partially wetting liquids on a rotating cylinder using a model that takes into account the effects of gravity, viscosity, rotation, surface tension and wettability. Such a system can be considered as a prototype for many other systems where the interplay of spatial heterogeneity and a lateral driving force in the proximity of a first- or second-order phase transition results in intricate behavior. So does a partially wetting drop on a rotating cylinder undergo a depinning transition as the rotation speed is increased, whereas for ideally wetting liquids the behavior \bfuwe{only changes quantitatively. We analyze the bifurcations that occur when the rotation speed is increased for several values of the equilibrium contact angle of the partially wetting liquids. This allows us to discuss how the entire bifurcation structure and the flow behavior it encodes changes with changing wettability. We employ various numerical continuation techniques that allow us to track stable/unstable steady and time-periodic film and drop thickness profiles. We support our findings by time-dependent numerical simulations and asymptotic analyses of steady and time-periodic profiles for large rotation numbers

The relation of steady evaporating drops fed by an influx and freely evaporating drops

We discuss a thin film evolution equation for a wetting evaporating liquid on a smooth solid substrate. The model is valid for slowly evaporating small sessile droplets when thermal effects are insignificant, while wettability and capillarity play a major role. The model is first employed to study steady evaporating drops that are fed locally through the substrate. An asymptotic analysis focuses on the precursor film and the transition region towards the bulk drop and a numerical continuation of steady drops determines their fully non-linear profiles. Following this, we study the time evolution of freely evaporating drops without influx for several initial drop shapes. As a result we find that drops initially spread if their initial contact angle is larger than the apparent contact angle of large steady evaporating drops with influx. Otherwise they recede right from the beginning