Aberrant water homeostasis detected by stable isotope analysis

Journal ArticleWhile 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 (d2H) and oxygen (d18O) isotope ratios in body water. Additionally, we show that the d2H and d18O 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

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

Colorado Plateau Coring Project, Phase I (CPCP-I): a continuously cored, globally exportable chronology of Triassic continental environmental change from western North America

Phase 1 of the Colorado Plateau Coring Project (CPCP-I) recovered a total of over 850&thinsp;m of stratigraphically overlapping core from three coreholes at two sites in the Early to Middle and Late Triassic age largely fluvial Moenkopi and Chinle formations in Petrified Forest National Park (PFNP), northeastern Arizona, USA. Coring took place during November and December of 2013 and the project is now in its post-drilling science phase. The CPCP cores have abundant detrital zircon-producing layers (with survey LA-ICP-MS dates selectively resampled for CA-ID-TIMS U-Pb ages ranging in age from at least 210 to 241&thinsp;Ma), which together with their magnetic polarity stratigraphy demonstrate that a globally exportable timescale can be produced from these continental sequences and in the process show that a prominent gap in the calibrated Phanerozoic record can be filled. The portion of core CPCP-PFNP13-1A for which the polarity stratigraphy has been completed thus far spans  ∼ 215 to 209&thinsp;Ma of the Late Triassic age, and strongly validates the longer Newark-Hartford Astrochronostratigraphic-calibrated magnetic Polarity Time-Scale (APTS) based on cores recovered in the 1990s during the Newark Basin Coring Project (NBCP).Core recovery was  ∼ 100&thinsp;% in all holes (Table 1). The coreholes were inclined  ∼ 60–75° approximately to the south to ensure azimuthal orientation in the nearly flat-lying bedding, critical to the interpretation of paleomagentic polarity stratigraphy. The two longest of the cores (CPCP-PFNP13-1A and 2B) were CT-scanned in their entirety at the University of Texas High Resolution X-ray CT Facility in Austin, TX, and subsequently along with 2A, all cores were split and processed at the CSDCO/LacCore Facility, in Minneapolis, MN, where they were scanned for physical property logs and imaging. While remaining the property of the Federal Government, the archive half of each core is curated at the NSF-sponsored LacCore Core Repository and the working half is stored at the Rutgers University Core Repository in Piscataway, NJ, where the initial sampling party was held in 2015 with several additional sampling events following. Additional planned study will recover the rest of the polarity stratigraphy of the cores as additional zircon ages, sedimentary structure and paleosol facies analysis, stable isotope geochemistry, and calibrated XRF core scanning are accomplished. Together with strategic outcrop studies in Petrified Forest National Park and environs, these cores will allow the vast amount of surface paleontological and paleoenvironmental information recorded in the continental Triassic of western North America to be confidently placed in a secure context along with important events such as the giant Manicouagan impact at  ∼ 215.5&thinsp;Ma (Ramezani et al., 2005) and long wavelength astronomical cycles pacing global environmental change and trends in atmospheric gas composition during the dawn of the dinosaurs.</p

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Variations in human body water isotope composition across the United States

Accurate human provenancing using stable isotopes depends directly on solid understandings of the geographic and individual factors affecting isotope variability and incorporation into human tissues. Transfer of isotopic, and therefore spatial, information between environmental water and biological tissues is mediated by the isotopic composition of body water. Thus, there is a need to study body water isotope ratios at a population level and over a large isotopic and geographic range. We evaluated oxygen (δ18Obw) and hydrogen (δ2Hbw) isotope values of body water from 72 volunteers in 10 different cities across the US, and over a 5–10-day period. We analyzed covariates (e.g., water intake, physical activity, biometrics, gender) that might explain individual stable isotope ratio variations and tested a predictive model that incorporates the δ-values of drinking water, food, and O2 as well as individual variables to predict the δ-values of body water. The individual variability in body water isotope values overtime (mean 0.3‰ for δ18Obw and 2.3‰ for δ2Hbw) was lower than the intra-city variability (mean 0.9‰ for δ18Obw and 6.9‰ for δ2Hbw). Body water isotope values differed among cities (ANOVA: δ18Obw F = 97.2, p < 0.001; δ2Hbw F = 176.2, p < 0.001). However, significant overlap among some cities with different drinking water was discovered. We detected significant covariation of measured drinking water and human body water isotope values (both isotope systems R2 ≥ 0.89, p < 0.001) and small but significant effects of the average daily exercise and amount of fluid intake. The differences between measured and model-predicted body water values (mean 0.12 ± 1.2‰ for Δδ18O and −1.2 ± 8.2‰ for Δδ2H) were statistically indistinguishable from zero (Δδ18O t = −0.751, p = 0.45; Δδ2H t = 1.133, p = 0.26). Here we show that community level variation exists in the δ18Obw and δ2Hbw values and the primary drivers are the regional differences in drinking water isotopes. Consistency of the body water isotope composition over the study period suggests that tissues would incorporate a stable isotope signal over time. The amount of drinking water and physical activity influence body water values, while the variation in the isotopic values of food may contribute to regional level variability, but that still remains to be assessed further. The human body water model provides accurate estimates for measured values, capturing and reproducing the main features of the body water isotope variation across space.Fil: Valenzuela, Luciano Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil; 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); Argentina. University Of Utah. School of Biological Sciences; Estados UnidosFil: O'Grady, Shannon P.. University Of Utah. School of Biological Sciences; Estados UnidosFil: Ehleringer, James R.. University Of Utah. School of Biological Sciences; Estados Unido

Process evaluation of a technology-delivered screening and brief intervention for substance use in primary care

Psychotherapy process research examines the content of treatment sessions and their association with outcomes in an attempt to better understand the interactions between therapists and clients, and to elucidate mechanisms of behavior change. A similar approach is possible in technology-delivered interventions, which have an interaction process that is always perfectly preserved and rigorously definable. The present study sought to examine the process of participants' interactions with a computer-delivered brief intervention for drug use, from a study comparing computer- and therapist-delivered brief interventions among adults at two primary health care centers in New Mexico. Specifically, we sought to describe the pattern of participants' (N = 178) choices and reactions throughout the computer-delivered brief intervention, and to examine associations between that process and intervention response at 3-month follow-up. Participants were most likely to choose marijuana as the first substance they wished to discuss (n = 114, 64.0%). Most participants indicated that they had not experienced any problems as a result of their drug use (n = 108, 60.7%), but nearly a third of these (n = 32, 29.6%) nevertheless indicated a desire to stop or reduce its use; participants who did report negative consequences were most likely to endorse financial or relationship concerns. However, participant ratings of the importance of change or of the helpfulness of personalized normed feedback were unrelated to changes in substance use frequency. Design of future e-interventions should consider emphasizing possible benefits of quitting rather than the negative consequences of drug use, and—when addressing consequences—should consider focusing on the impacts of substance use on relationship and financial aspects. These findings are an early but important step toward using process evaluation to optimize e-intervention content

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