Supplemental files for Eating versus skipping breakfast has no discernible effect on obesity-related anthropometric outcomes: a systematic review and meta-analysis.

These are the supplemental files for the manuscript entitled, Eating versus skipping breakfast has no discernible effect on obesity-related anthropometric outcomes: a systematic review and meta-analysis. To calculate the meta-analyses: calculations.R - Updated. Calculates individual effect sizes for each study; this file is sourced by metaanalysis with subgroup.R; update to account for updates to the data for Neumann et al. 2016. metaanalysis with subgroup and cumulative.R - updated from metaanalysis.R from version 1 and metaanalysis with subgroup.R from version 2. Reproduces the composite forest plot, summary table, and outputs. Includes a subgroup analysis stratified by baseline breakfast habit, and tests for the interaction between baseline habit and assigned breakfast condition. Now includes a cumulative analysis in which studies are added based on duration, from longest to shortest. neumann2016.csv - updated. Contains the raw data from Neumann et al. 2016, incorporating the corrections sent to us by the authors rho estimates for farshchi.R - Uses data from Geliebter et al. to estimate within-condition pre-post correlations; these calculations are manually included in calculations.R. PRISMA checklist.doc is the PRISMA checklist for the article with sections listed instead of page numbers, given that page numbers may change depending on viewing format. Updated with the subgroup analysis. Subgroup analysis - methods and results.pdf describes the methods and results of the subgroup analysis testing the interaction between baseline breakfast habits and assigned breakfast habits. Includes forest plots and summary table for the five anthropometric measurements that had enough comparisons to estimate an effect: body weight, BMI, body fat percentage, fat mass, lean mass. Cumulative analysis - methods and results.pdf describes the methods and results of the cumulative meta-analysis in which studies were added based on study duration from longest to shortest. Includes cumulative plots for the two anthropometric measurements that had enough comparisons for a meaningful cumulative analysis: body weight and BMI

Glucose Signaling Is Important for Nutrient Adaptation during Differentiation of Pleomorphic African Trypanosomes

The African trypanosome has evolved mechanisms to adapt to changes in nutrient availability that occur during its life cycle. During transition from mammalian blood to insect vector gut, parasites experience a rapid reduction in environmental glucose. Here we describe how pleomorphic parasites respond to glucose depletion with a focus on parasite changes in energy metabolism and growth. Long slender bloodstream form parasites were rapidly killed as glucose concentrations fell, while short stumpy bloodstream form parasites persisted to differentiate into the insect-stage procyclic form parasite. The rate of differentiation was lower than that triggered by other cues but reached physiological rates when combined with cold shock. Both differentiation and growth of resulting procyclic form parasites were inhibited by glucose and nonmetabolizable glucose analogs, and these parasites were found to have upregulated amino acid metabolic pathway component gene expression. In summary, glucose transitions from the primary metabolite of the blood-stage infection to a negative regulator of cell development and growth in the insect vector, suggesting that the hexose is not only a key metabolic agent but also an important signaling molecule

Shotgun Kinetic Target-Guided Synthesis Approach Enables the Discovery of Small-Molecule Inhibitors against Pathogenic Free-Living Amoeba Glucokinases

Pathogenic free-living amoebae (pFLA) can cause life-threatening central nervous system (CNS) infections and warrant the investigation of new chemical agents to combat the rise of infection from these pathogens. Naegleria fowleri glucokinase (NfGlck), a key metabolic enzyme involved in generating glucose-6-phosphate, was previously identified as a potential target due to its limited sequence similarity with human Glck (HsGlck). Herein, we used our previously demonstrated multifragment kinetic target-guided synthesis (KTGS) screening strategy to identify inhibitors against pFLA glucokinases. Unlike the majority of previous KTGS reports, our current study implements a “shotgun” approach, where fragments were not biased by predetermined binding potentials. The study resulted in the identification of 12 inhibitors against 3 pFLA glucokinase enzymesNfGlck, Balamuthia mandrillaris Glck (BmGlck), and Acanthamoeba castellanii Glck (AcGlck). This work demonstrates the utility of KTGS to identify small-molecule binders for biological targets where resolved X-ray crystal structures are not readily accessible

Shotgun Kinetic Target-Guided Synthesis Approach Enables the Discovery of Small-Molecule Inhibitors against Pathogenic Free-Living Amoeba Glucokinases

Pathogenic free-living amoebae (pFLA) can cause life-threatening central nervous system (CNS) infections and warrant the investigation of new chemical agents to combat the rise of infection from these pathogens. Naegleria fowleri glucokinase (NfGlck), a key metabolic enzyme involved in generating glucose-6-phosphate, was previously identified as a potential target due to its limited sequence similarity with human Glck (HsGlck). Herein, we used our previously demonstrated multifragment kinetic target-guided synthesis (KTGS) screening strategy to identify inhibitors against pFLA glucokinases. Unlike the majority of previous KTGS reports, our current study implements a “shotgun” approach, where fragments were not biased by predetermined binding potentials. The study resulted in the identification of 12 inhibitors against 3 pFLA glucokinase enzymesNfGlck, Balamuthia mandrillaris Glck (BmGlck), and Acanthamoeba castellanii Glck (AcGlck). This work demonstrates the utility of KTGS to identify small-molecule binders for biological targets where resolved X-ray crystal structures are not readily accessible