Three weeks of interrupting sitting lowers fasting glucose and glycemic variability, but not glucose tolerance, in free-living women and men with obesity

Funding This work was supported by grants from the Novo Nordisk Foundation (NNF14OC0011493, NNF14OC0009941, NNF18CC0034900), Swedish Diabetes Foundation (DIA2018-357), Diabetes Wellness Sverige (1849-PG), Swedish Research Council (2015-00165, 2018-02389), the Strategic Research Programme in Diabetes at Karolinska Institutet (2009-1068), the Knut and Alice Wallenberg Foundation (2018-0094), and the Stockholm County Council (SLL20170159). D.D. is supported by the National Health and Medical Research Council and the Victorian Government’s OIS scheme. Acknowledgements We thank the Swedish Metabolomics Centre (Umeå University) for assisting with the lipidomic analysis and Mariam Nordstrand for efforts in the recruitment and screening of participants, and in muscle biopsy procedure. The current addresses for S.P. and B.M.G. are the School of Life Sciences, University of Nottingham, Nottingham, UK, and The Rowett Institute, University of Aberdeen, Aberdeen, UK, respectively.Peer reviewedPostprin

On the magnetic fields generated by experimental dynamos

We review the results obtained by three successful fluid dynamo experiments and discuss what has been learnt from them about the effect of turbulence on the dynamo threshold and saturation. We then discuss several questions that are still open and propose experiments that could be performed to answer some of them.Comment: 40 pages, 13 figure

Bottom mixed layer oxygen dynamics in the Celtic Sea

The seasonally stratified continental shelf seas are highly productive, economically important environments which are under considerable pressure from human activity. Global dissolved oxygen concentrations have shown rapid reductions in response to anthropogenic forcing since at least the middle of the twentieth century. Oxygen consumption is at the same time linked to the cycling of atmospheric carbon, with oxygen being a proxy for carbon remineralisation and the release of CO2. In the seasonally stratified seas the bottom mixed layer (BML) is partially isolated from the atmosphere and is thus controlled by interplay between oxygen consumption processes, vertical and horizontal advection. Oxygen consumption rates can be both spatially and temporally dynamic, but these dynamics are often missed with incubation based techniques. Here we adopt a Bayesian approach to determining total BML oxygen consumption rates from a high resolution oxygen time-series. This incorporates both our knowledge and our uncertainty of the various processes which control the oxygen inventory. Total BML rates integrate both processes in the water column and at the sediment interface. These observations span the stratified period of the Celtic Sea and across both sandy and muddy sediment types. We show how horizontal advection, tidal forcing and vertical mixing together control the bottom mixed layer oxygen concentrations at various times over the stratified period. Our muddy-sand site shows cyclic spring-neap mediated changes in oxygen consumption driven by the frequent resuspension or ventilation of the seabed. We see evidence for prolonged periods of increased vertical mixing which provide the ventilation necessary to support the high rates of consumption observed

First trimester diagnosis and screening for fetal aneuploidy

Maternal serum screening for neural tube defects and fetal aneuploidy in the second trimester has been incorporated into obstetrical practice over the past two decades. Now, as a result of several multicenter trials, first trimester screening between 11 and 14 weeks has been shown to be an effective and reliable screening test for Down syndrome and trisomy 18. Benefits of first trimester screening include earlier identification of the pregnancy at risk for fetal aneuploidy and anatomic defects, in particular, cardiac anomalies, and the option of earlier diagnosis by chorionic villus sampling, if available. This policy updates the American College of Medical Genetics policy statement entitled Second Trimester Maternal Serum Screening for Fetal Open Neural Tube Defects and Aneuploidy (2004) and complements the sections of American College of Medical Genetic’s Standards and Guidelines for Clinical Genetics Laboratories entitled “Prenatal screening for Down syndrome that includes first trimester biochemistry and/or ultrasound measurements.

Lung adenocarcinoma originates from retrovirus infection of proliferating type 2 pneumocytes during pulmonary post-natal development or tissue repair

Jaagsiekte sheep retrovirus (JSRV) is a unique oncogenic virus with distinctive biological properties. JSRV is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, OPA) and possessing a major structural protein that functions as a dominant oncoprotein. Lung cancer is the major cause of death among cancer patients. OPA can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmonary carcinogenesis. In this study, we demonstrated that lung adenocarcinoma in sheep originates from infection and transformation of proliferating type 2 pneumocytes (termed here lung alveolar proliferating cells, LAPCs). We excluded that OPA originates from a bronchioalveolar stem cell, or from mature post-mitotic type 2 pneumocytes or from either proliferating or non-proliferating Clara cells. We show that young animals possess abundant LAPCs and are highly susceptible to JSRV infection and transformation. On the contrary, healthy adult sheep, which are normally resistant to experimental OPA induction, exhibit a relatively low number of LAPCs and are resistant to JSRV infection of the respiratory epithelium. Importantly, induction of lung injury increased dramatically the number of LAPCs in adult sheep and rendered these animals fully susceptible to JSRV infection and transformation. Furthermore, we show that JSRV preferentially infects actively dividing cell in vitro. Overall, our study provides unique insights into pulmonary biology and carcinogenesis and suggests that JSRV and its host have reached an evolutionary equilibrium in which productive infection (and transformation) can occur only in cells that are scarce for most of the lifespan of the sheep. Our data also indicate that, at least in this model, inflammation can predispose to retroviral infection and cancer

Prevalence of Disorders Recorded in Dogs Attending Primary-Care Veterinary Practices in England

Purebred dog health is thought to be compromised by an increasing occurence of inherited diseases but inadequate prevalence data on common disorders have hampered efforts to prioritise health reforms. Analysis of primary veterinary practice clinical data has been proposed for reliable estimation of disorder prevalence in dogs. Electronic patient record (EPR) data were collected on 148,741 dogs attending 93 clinics across central and south-eastern England. Analysis in detail of a random sample of EPRs relating to 3,884 dogs from 89 clinics identified the most frequently recorded disorders as otitis externa (prevalence 10.2%, 95% CI: 9.1-11.3), periodontal disease (9.3%, 95% CI: 8.3-10.3) and anal sac impaction (7.1%, 95% CI: 6.1-8.1). Using syndromic classification, the most prevalent body location affected was the head-and-neck (32.8%, 95% CI: 30.7-34.9), the most prevalent organ system affected was the integument (36.3%, 95% CI: 33.9-38.6) and the most prevalent pathophysiologic process diagnosed was inflammation (32.1%, 95% CI: 29.8-34.3). Among the twenty most-frequently recorded disorders, purebred dogs had a significantly higher prevalence compared with crossbreds for three: otitis externa (P = 0.001), obesity (P = 0.006) and skin mass lesion (P = 0.033), and popular breeds differed significantly from each other in their prevalence for five: periodontal disease (P = 0.002), overgrown nails (P = 0.004), degenerative joint disease (P = 0.005), obesity (P = 0.001) and lipoma (P = 0.003). These results fill a crucial data gap in disorder prevalence information and assist with disorder prioritisation. The results suggest that, for maximal impact, breeding reforms should target commonly-diagnosed complex disorders that are amenable to genetic improvement and should place special focus on at-risk breeds. Future studies evaluating disorder severity and duration will augment the usefulness of the disorder prevalence information reported herein

Customized birth weight for gestational age standards: Perinatal mortality patterns are consistent with separate standards for males and females but not for blacks and whites

BACKGROUND: Some currently available birth weight for gestational age standards are customized but others are not. We carried out a study to provide empirical justification for customizing such standards by sex and for whites and blacks in the United States. METHODS: We studied all male and female singleton live births and stillbirths (22 or more weeks of gestation; 500 g birth weight or over) in the United States in 1997 and 1998. White and black singleton live births and stillbirths were also examined. Qualitative congruence between gestational age-specific growth restriction and perinatal mortality rates was used as the criterion for identifying the preferred standard. RESULTS: The fetuses at risk approach showed that males had higher perinatal mortality rates at all gestational ages compared with females. Gestational age-specific growth restriction rates based on a sex-specific standard were qualitatively consistent with gestational age-specific perinatal mortality rates among males and females. However, growth restriction patterns among males and females based on a unisex standard could not be reconciled with perinatal mortality patterns. Use of a single standard for whites and blacks resulted in gestational age-specific growth restriction rates that were qualitatively congruent with patterns of perinatal mortality, while use of separate race-specific standards led to growth restriction patterns that were incompatible with patterns of perinatal mortality. CONCLUSION: Qualitative congruence between growth restriction and perinatal mortality patterns provides an outcome-based justification for sex-specific birth weight for gestational age standards but not for the available race-specific standards for blacks and whites in the United States

The yeast P5 type ATPase, Spf1, regulates manganese transport into the endoplasmic reticulum

The endoplasmic reticulum (ER) is a large, multifunctional and essential organelle. Despite intense research, the function of more than a third of ER proteins remains unknown even in the well-studied model organism Saccharomyces cerevisiae. One such protein is Spf1, which is a highly conserved, ER localized, putative P-type ATPase. Deletion of SPF1 causes a wide variety of phenotypes including severe ER stress suggesting that this protein is essential for the normal function of the ER. The closest homologue of Spf1 is the vacuolar P-type ATPase Ypk9 that influences Mn2+ homeostasis. However in vitro reconstitution assays with Spf1 have not yielded insight into its transport specificity. Here we took an in vivo approach to detect the direct and indirect effects of deleting SPF1. We found a specific reduction in the luminal concentration of Mn2+ in ∆spf1 cells and an increase following it’s overexpression. In agreement with the observed loss of luminal Mn2+ we could observe concurrent reduction in many Mn2+-related process in the ER lumen. Conversely, cytosolic Mn2+-dependent processes were increased. Together, these data support a role for Spf1p in Mn2+ transport in the cell. We also demonstrate that the human sequence homologue, ATP13A1, is a functionally conserved orthologue. Since ATP13A1 is highly expressed in developing neuronal tissues and in the brain, this should help in the study of Mn2+-dependent neurological disorders