New challenges in studying nutrition-disease interactions in the developing world.

Latest estimates indicate that nutritional deficiencies account for 3 million child deaths each year in less-developed countries. Targeted nutritional interventions could therefore save millions of lives. However, such interventions require careful optimization to maximize benefit and avoid harm. Progress toward designing effective life-saving interventions is currently hampered by some serious gaps in our understanding of nutrient metabolism in humans. In this Personal Perspective, we highlight some of these gaps and make some proposals as to how improved research methods and technologies can be brought to bear on the problems of undernourished children in the developing world

Transferable interactions of Li+ and Mg2+ ions in polarizable models

Therapeutic implications of Li(+), in many cases, stem from its ability to inhibit certain Mg(2+)-dependent enzymes, where it interacts with or substitutes for Mg(2+). The underlying details of its action are, however, unknown. Molecular simulations can provide insights, but their reliability depends on how well they describe relative interactions of Li(+) and Mg(2+) with water and other biochemical groups. Here, we explore, benchmark, and recommend improvements to two simulation approaches: the one that employs an all-atom polarizable molecular mechanics (MM) model and the other that uses a hybrid quantum and MM implementation of the quasi-chemical theory (QCT). The strength of the former is that it describes thermal motions explicitly and that of the latter is that it derives local contributions from electron densities. Reference data are taken from the experiment, and also obtained systematically from CCSD(T) theory, followed by a benchmarked vdW-inclusive density functional theory. We find that the QCT model predicts relative hydration energies and structures in agreement with the experiment and without the need for additional parameterization. This implies that accurate descriptions of local interactions are essential. Consistent with this observation, recalibration of local interactions in the MM model, which reduces errors from 10.0 kcal/mol to 1.4 kcal/mol, also fixes aqueous phase properties. Finally, we show that ion–ligand transferability errors in the MM model can be reduced significantly from 10.3 kcal/mol to 1.2 kcal/mol by correcting the ligand’s polarization term and by introducing Lennard-Jones cross-terms. In general, this work sets up systematic approaches to evaluate and improve molecular models of ions binding to proteins

Acute effects of a thermogenic nutritional supplement on cycling time to exhaustion and muscular strength in college-aged men

<p>Abstract</p> <p>Background</p> <p>The purpose of the present study was to examine the acute effects of a thermogenic nutritional supplement containing caffeine, capsaicin, bioperine, and niacin on muscular strength and endurance performance.</p> <p>Methods</p> <p>Twenty recreationally-active men (mean ± SD age = 21.5 ± 1.4 years; stature = 178.2 ± 6.3 cm; mass = 76.5 ± 9.9 kg; VO_{2 PEAK}= 3.05 ± 0.59 L/min^-1) volunteered to participate in this randomized, double-blinded, placebo-controlled, cross-over study. All testing took place over a three-week period, with each of the 3 laboratory visits separated by 7 days (± 2 hours). During the initial visit, a graded exercise test was performed on a Lode Corival cycle ergometer (Lode, Groningen, Netherlands) until exhaustion (increase of 25 W every 2 min) to determine the maximum power output (W) at the VO_{2 PEAK}(Parvo Medics TrueOne^®2400 Metabolic Measurement System, Sandy, Utah). In addition, one-repetition maximum (1-RM) strength was assessed using the bench press (BP) and leg press (LP) exercises. During visits 2 and 3, the subjects were asked to consume a capsule containing either the active supplement (200 mg caffeine, 33.34 mg capsaicin, 5 mg bioperine, and 20 mg niacin) or the placebo (175 mg of calcium carbonate, 160 mg of microcrystalline cellulose, 5 mg of stearic acid, and 5 mg of magnesium stearate in an identical capsule) 30 min prior to the testing. Testing included a time-to-exhaustion (TTE) ride on a cycle ergometer at 80% of the previously-determined power output at VO_{2 PEAK}followed by 1-RM LP and BP tests.</p> <p>Results</p> <p>There were no differences (<it>p </it>> 0.05) between the active and placebo trials for BP, LP, or TTE. However, for the BP and LP scores, the baseline values (visit 1) were less than the values recorded during visits 2 and 3 (<it>p </it>≤ 0.05).</p> <p>Conclusion</p> <p>Our findings indicated that the active supplement containing caffeine, capsaicin, bioperine, and niacin did not alter muscular strength or cycling endurance when compared to a placebo trial. The lack of increases in BP and LP strength and cycle ergometry endurance elicited by this supplement may have been related to the relatively small dose of caffeine, the high intensity of exercise, the untrained status of the participants, and/or the potential for caffeine and capsaicin to increase carbohydrate oxidation.</p

Acute effects of a thermogenic nutritional supplement on cycling time to exhaustion and muscular strength in college-aged men

This is the publisher's version, also available electronically from http://www.jissn.com/content/6/1/15.The purpose of the present study was to examine the acute effects of a thermogenic nutritional supplement containing caffeine, capsaicin, bioperine, and niacin on muscular strength and endurance performance. Methods Twenty recreationally-active men (mean ± SD age = 21.5 ± 1.4 years; stature = 178.2 ± 6.3 cm; mass = 76.5 ± 9.9 kg; VO2 PEAK = 3.05 ± 0.59 L/min-1) volunteered to participate in this randomized, double-blinded, placebo-controlled, cross-over study. All testing took place over a three-week period, with each of the 3 laboratory visits separated by 7 days (± 2 hours). During the initial visit, a graded exercise test was performed on a Lode Corival cycle ergometer (Lode, Groningen, Netherlands) until exhaustion (increase of 25 W every 2 min) to determine the maximum power output (W) at the VO2 PEAK (Parvo Medics TrueOne® 2400 Metabolic Measurement System, Sandy, Utah). In addition, one-repetition maximum (1-RM) strength was assessed using the bench press (BP) and leg press (LP) exercises. During visits 2 and 3, the subjects were asked to consume a capsule containing either the active supplement (200 mg caffeine, 33.34 mg capsaicin, 5 mg bioperine, and 20 mg niacin) or the placebo (175 mg of calcium carbonate, 160 mg of microcrystalline cellulose, 5 mg of stearic acid, and 5 mg of magnesium stearate in an identical capsule) 30 min prior to the testing. Testing included a time-to-exhaustion (TTE) ride on a cycle ergometer at 80% of the previously-determined power output at VO2 PEAK followed by 1-RM LP and BP tests. Results There were no differences (p > 0.05) between the active and placebo trials for BP, LP, or TTE. However, for the BP and LP scores, the baseline values (visit 1) were less than the values recorded during visits 2 and 3 (p ≤ 0.05). Conclusion Our findings indicated that the active supplement containing caffeine, capsaicin, bioperine, and niacin did not alter muscular strength or cycling endurance when compared to a placebo trial. The lack of increases in BP and LP strength and cycle ergometry endurance elicited by this supplement may have been related to the relatively small dose of caffeine, the high intensity of exercise, the untrained status of the participants, and/or the potential for caffeine and capsaicin to increase carbohydrate oxidation

Strengthening Public Health in Wisconsin Through the Wisconsin Clinical Laboratory Network

The Wisconsin Clinical Laboratory Network (WCLN) at the University of Wisconsin–Madison is a partnership of 138 clinical and public health laboratories (as of February 2019) coordinated by the Wisconsin State Laboratory of Hygiene. This article describes the WCLN, its current activities, and lessons learned through this partnership. A laboratory technical advisory group, which consists of representatives from clinical laboratories, provides clinical laboratory perspective to the WCLN and fosters communication among laboratories. Activities and resources available through the WCLN include annual regional meetings, annual technical workshops, webinars, an email listserv, laboratory informational messages, in-person visits by a WCLN coordinator to clinical laboratories, and laboratory-based surveillance data and summaries distributed by the Wisconsin State Laboratory of Hygiene. One challenge to maintaining the WCLN is securing continual funding for network activities. Key lessons learned from this partnership of more than 20 years include the importance of in-person meetings, the clinical perspective of the laboratory technical advisory group, and providing activities and resources to clinical laboratories to foster sharing of data and clinical specimens for public health surveillance and outbreak response

Percent body fat estimations in college men using field and laboratory methods: A three-compartment model approach

Background: Methods used to estimate percent body fat can be classified as a laboratory or field technique. However, the validity of these methods compared to multiple-compartment models has not been fully established. The purpose of this study was to determine the validity of field and laboratory methods for estimating percent fat (%fat) in healthy college-age men compared to the Siri three-compartment model (3C). Methods: Thirty-one Caucasian men (22.5 ± 2.7 yrs; 175.6 ± 6.3 cm; 76.4 ± 10.3 kg) had their %fat estimated by bioelectrical impedance analysis (BIA) using the BodyGram™ computer program (BIA-AK) and population-specific equation (BIA-Lohman), near-infrared interactance (NIR) (Futrex® 6100/XL), four circumference-based military equations [Marine Corps (MC), Navy and Air Force (NAF), Army (A), and Friedl], air-displacement plethysmography (BP), and hydrostatic weighing (HW). Results: All circumference-based military equations (MC = 4.7% fat, NAF = 5.2% fat, A = 4.7% fat, Friedl = 4.7% fat) along with NIR (NIR = 5.1% fat) produced an unacceptable total error (TE). Both laboratory methods produced acceptable TE values (HW = 2.5% fat; BP = 2.7% fat). The BIA-AK, and BIA-Lohman field methods produced acceptable TE values (2.1% fat). A significant difference was observed for the MC and NAF equations compared to both the 3C model and HW (p < 0.006). Conclusion: Results indicate that the BP and HW are valid laboratory methods when compared to the 3C model to estimate %fat in college-age Caucasian men. When the use of a laboratory method is not feasible, BIA-AK, and BIA-Lohman are acceptable field methods to estimate %fat in this population

Managing hybridization of a recovering endangered species: The red wolf \u3ci\u3eCanis rufus\u3c/i\u3e as a case study

Hybridization presents a unique challenge for conservation biologists and managers. While hybridization is an important evolutionary process, hybridization is also a threat formany native species. The endangered species recovery effort for the red wolf Canis rufus is a classic system for understanding and addressing the challenges of hybridization. From 1987‒1993, 63 red wolves were released from captivity in eastern North Carolina, USA, to establish a free-ranging, non-essential experimental population. By 1999, managers recognized hybridization with invasive coyotes Canis latrans was the single greatest threat to successful recovery, and an adaptive management plan was adopted with innovative approaches for managing the threat of hybridization. Here we review the application and results of the adaptive management efforts from 1993 to 2013 by comparing: (1) the numbers of wolves, coyotes, and hybrids captured, (2) the numbers of territorial social groups with presumed breeding capabilities, (3) the number of red wolf and hybrid litters documented each year and (4) the degree of coyote introgression into the wild red wolf gene pool. We documented substantial increases in the number of known red wolves and red wolf social groups from 1987–2004 followed by a plateau and slight decline by 2013.The number of red wolf litters exceeded hybrid litters each year and the proportion of hybrid litters per year averaged 21%. The genetic composition of the wild red wolf population is estimated to include \u3c 4% coyote ancestry from recent introgression since reintroduction. We conclude that the adaptive management plan was effective at reducing the introgression of coyote genes into the red wolf population, but population recovery of red wolves will require continuation of the current management plan, or alternative approaches, for the foreseeable future. More broadly, we discuss the lessons learned from red wolf adaptive management that could assist other endangered species recovery efforts facing the challenge of minimizing hybridizatio

The scale of population structure in Arabidopsis thaliana

The population structure of an organism reflects its evolutionary history and influences its evolutionary trajectory. It constrains the combination of genetic diversity and reveals patterns of past gene flow. Understanding it is a prerequisite for detecting genomic regions under selection, predicting the effect of population disturbances, or modeling gene flow. This paper examines the detailed global population structure of Arabidopsis thaliana. Using a set of 5,707 plants collected from around the globe and genotyped at 149 SNPs, we show that while A. thaliana as a species self-fertilizes 97% of the time, there is considerable variation among local groups. This level of outcrossing greatly limits observed heterozygosity but is sufficient to generate considerable local haplotypic diversity. We also find that in its native Eurasian range A. thaliana exhibits continuous isolation by distance at every geographic scale without natural breaks corresponding to classical notions of populations. By contrast, in North America, where it exists as an exotic species, A. thaliana exhibits little or no population structure at a continental scale but local isolation by distance that extends hundreds of km. This suggests a pattern for the development of isolation by distance that can establish itself shortly after an organism fills a new habitat range. It also raises questions about the general applicability of many standard population genetics models. Any model based on discrete clusters of interchangeable individuals will be an uneasy fit to organisms like A. thaliana which exhibit continuous isolation by distance on many scales

Genome-wide association Scan of dental caries in the permanent dentition

Background: Over 90% of adults aged 20 years or older with permanent teeth have suffered from dental caries leading to pain, infection, or even tooth loss. Although caries prevalence has decreased over the past decade, there are still about 23% of dentate adults who have untreated carious lesions in the US. Dental caries is a complex disorder affected by both individual susceptibility and environmental factors. Approximately 35-55% of caries phenotypic variation in the permanent dentition is attributable to genes, though few specific caries genes have been identified. Therefore, we conducted the first genome-wide association study (GWAS) to identify genes affecting susceptibility to caries in adults. Methods: Five independent cohorts were included in this study, totaling more than 7000 participants. For each participant, dental caries was assessed and genetic markers (single nucleotide polymorphisms, SNPs) were genotyped or imputed across the entire genome. Due to the heterogeneity among the five cohorts regarding age, genotyping platform, quality of dental caries assessment, and study design, we first conducted genome-wide association (GWA) analyses on each of the five independent cohorts separately. We then performed three meta-analyses to combine results for: (i) the comparatively younger, Appalachian cohorts (N = 1483) with well-assessed caries phenotype, (ii) the comparatively older, non-Appalachian cohorts (N = 5960) with inferior caries phenotypes, and (iii) all five cohorts (N = 7443). Top ranking genetic loci within and across meta-analyses were scrutinized for biologically plausible roles on caries. Results: Different sets of genes were nominated across the three meta-analyses, especially between the younger and older age cohorts. In general, we identified several suggestive loci (P-value ≤ 10E-05) within or near genes with plausible biological roles for dental caries, including RPS6KA2 and PTK2B, involved in p38-depenedent MAPK signaling, and RHOU and FZD1, involved in the Wnt signaling cascade. Both of these pathways have been implicated in dental caries. ADMTS3 and ISL1 are involved in tooth development, and TLR2 is involved in immune response to oral pathogens. Conclusions: As the first GWAS for dental caries in adults, this study nominated several novel caries genes for future study, which may lead to better understanding of cariogenesis, and ultimately, to improved disease predictions, prevention, and/or treatment