Aberrant Water Homeostasis Detected by Stable Isotope Analysis

While isotopes are frequently used as tracers in investigations of disease physiology (i.e., 14C labeled glucose), few studies have examined the impact that disease, and disease-related alterations in metabolism, may have on stable isotope ratios at natural abundance levels. The isotopic composition of body water is heavily influenced by water metabolism and dietary patterns and may provide a platform for disease detection. By utilizing a model of streptozotocin (STZ)-induced diabetes as an index case of aberrant water homeostasis, we demonstrate that untreated diabetes mellitus results in distinct combinations, or signatures, of the hydrogen (δ2H) and oxygen (δ18O) isotope ratios in body water. Additionally, we show that the δ2H and δ18O values of body water are correlated with increased water flux, suggesting altered blood osmolality, due to hyperglycemia, as the mechanism behind this correlation. Further, we present a mathematical model describing the impact of water flux on the isotopic composition of body water and compare model predicted values with actual values. These data highlight the importance of factors such as water flux and energy expenditure on predictive models of body water and additionally provide a framework for using naturally occurring stable isotope ratios to monitor diseases that impact water homeostasis

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

Evaluation of childhood nutrition by dietary survey and stable isotope analyses of hair and breath

Objectives: The natural abundances of carbon, nitrogen, and sulfur stable isotopes in hair, and of carbon isotopes in breath serve as quantitative biomarkers of protein and carbohydrate sources, but applicability of isotopes for evaluating children's diet has not been demonstrated. In this study, we sought to describe the stable isotope patterns observed in the hair and breath of children and to assess dietary variations in relation to age and ethnicity, hypothesizing that these would reflect dietary differences across age and ethnic groups and would correlate with intake variables derived from a Food Frequency Questionnaire. Methods: Data were obtained from a cross-sectional study of non-Hispanic white (N = 115) and Hispanic (N = 97) children, aged 9–16 years, in Salt Lake City, Utah. Sampling included a hair sample, breath samples (AM and PM), and a youth/adolescent food questionnaire (YAQ). Hair was analyzed for carbon (δ13C), nitrogen (δ15N), and sulfur (δ34S) isotopes, and breath samples for δ13CAM/PM of respired CO2. Results: Non-Hispanic whites had lower δ13C, δ15N, δ13CAM, and δ13CPM values than Hispanics. Hair δ13C and δ15N values were correlated with protein sources, particularly for non-Hispanics. Breath δ13C values were correlated with carbohydrate sources, particularly for Hispanic students. Non-Hispanic white students reported greater intake of total protein, animal protein, dairy, and grain than Hispanic students. Hispanic students reported higher intake of carbohydrates, particularly sweetened beverages. Conclusion: While YAQ and stable isotope data reflected strong cultural influences in diet, no significant gender-based nor age-based differences were detected. Significant covariation between YAQ and isotopes existed and demonstrate the potential of stable isotopes for characterizing children's diet.Fil: Valenzuela, Luciano Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Sociales. Departamento de Arqueología. Laboratorio de Ecología Evolutiva Humana (Sede Quequén); ArgentinaFil: O'Grady, Shannon P.. University Of Utah. Department Of Biology; Estados UnidosFil: Enright, Lindsey E.. University Of Utah. Department Of Biology; Estados UnidosFil: Murtaugh, Maureen. Huntsman Cancer Institute; Estados UnidosFil: Sweeney, Carol. Huntsman Cancer Institute; Estados UnidosFil: Ehleringer, James R.. University Of Utah. Department Of Biology; Estados Unido

Isotopic values of body water relative to blood glucose.

<p>Isotopic signature of body water (y1 axis) and blood glucose values (y2 axis) over the 5 week study period relative to the isotopic signature of drinking water (−DW). Time 0 is prior to STZ treatment. (A) δ²H of body water and blood glucose values of VEH treated (○ and □, respectively; n = 7) and STZ treated (• and ▪, respectively; n = 6) mice. (B) δ¹⁸O of body water and blood glucose values of VEH treated (○ and □, respectively ; n = 7) and STZ treated (• and ▪, respectively; n = 6) mice. Bars delineate standard deviation for duplicate sample analyses.</p

Isotopic values of continental tap water relative to body water.

<p>Measured δ²H and δ¹⁸O values of tap water samples collected from 18 states across the continental United States (•) and body water (urine) samples collected within Salt Lake City, Utah (○). The simple linear regression between the hydrogen and oxygen of tap water (δ²H = 8.06¹⁸O+6.15, r² = 0.992) and body water (δ²H = 8.91δ¹⁸O−9.72, r² = 0.962) are also shown.</p

Isotopic values of body water relative to model predictions.

<p>Isotopic signature of body water of VEH (○) and STZ (•) mice relative to body water model predictions in which the only model variant is water influx. (A) Measured δ²H relative to δ¹⁸O of body water for all animals over the entire 5-week study period. The curve depicts model predictions for δ²H and δ¹⁸O values over a range of water influx values. (B) Measured δ²H values of body water and (C) δ¹⁸O values of body water relative to average drinking water per day of 9 individual animals (mL/day). The bold curve on each panel indicates values predicted by our mathematical model of the isotopic composition of body water using a total energy expenditure (TEE) of 37.4 KJ/day. Correlations between the model and measured δ²H and δ¹⁸O of body water yielded an r² = 0.83 and r² = 0.79, respectively. The lighter curve on each panel indicates values predicted by our mathematical model of the isotopic composition of body water using a TEE of 65.0 KJ/day. Correlations between the model and measured δ²H and δ¹⁸O of body water yielded an r² = 0.96 and r² = 0.96, respectively. Bars delineate standard deviation for sample analyses.</p

Values used in body water modeling.

<p>Where applicable, values for modeling exercises completed with a total energy expenditure of 37.4 and 65.0 KJ/day are included.</p

Water flux of VEH and STZ mice.

<p>Average water intake (▪) and urine output (□) from VEH treated (n = 6) and STZ treated mice (n = 6), at 1 week and 4 weeks post-injection. Bars delineate standard deviation within each group. Urine output from VEH treated mice was less than 5ml/day and below measurement precision.</p

The TB structural genomics consortium: a decade of progress

The TB Structural Genomics Consortium is a worldwide organization of collaborators whose mission is the comprehensive structural determination and analyses of Mycobacterium tuberculosis proteins to ultimately aid in tuberculosis diagnosis and treatment. Congruent to the overall vision, Consortium members have additionally established an integrated facilities core to streamline M. tuberculosis structural biology and developed bioinformatics resources for data mining. This review aims to share the latest Consortium developments with the TB community, including recent structures of proteins that play significant roles within M. tuberculosis. Atomic resolution details may unravel mechanistic insights and reveal unique and novel protein features, as well as important protein-protein and protein-ligand interactions, which ultimately lead to a better understanding of M. tuberculosis biology and may be exploited for rational, structure-based therapeutics design.Nicholas Chim ... John Bruning ... et al