Discovery of new mutually orthogonal bioorthogonal cycloaddition pairs through computational screening.

Density functional theory (DFT) calculations and experiments in tandem led to discoveries of new reactivities and selectivities involving bioorthogonal sydnone cycloadditions. Dibenzocyclooctyne derivatives (DIBAC and BARAC) were identified to be especially reactive dipolarophiles, which undergo the (3+2) cycloadditions with N-phenyl sydnone with the rate constant of up to 1.46 M-1 s-1. Most signifcantly, the sydnone-dibenzocyclooctyne and norbornene-tetrazine cycloadditions were predicted to be mutually orthogonal. This was validated experimentally and used for highly selective fluorescence labeling of two proteins simultaneously

The Acute Effect of Magnesium Supplementation on Endothelial Function: A randomized cross-over pilot study

: Magnesium (Mg) deficiency might be a catalyst in the process of endothelial dysfunction, an early event in the pathogenesis of atherosclerosis. The aim of this study was to determine the acute effect of an oral Mg supplement as compared to control on endothelial function assessed by flow-mediated dilatation (FMD). Nineteen participants (39 years, body mass index (BMI) 22.9 kg/m2 ) completed this randomized cross-over study. Blood pressure (BP) and FMD were measured and blood samples were taken before participants drank 200 mL water, with or without an over the counter Mg supplement (450 mg and 300 mg for men and women). Measurements were repeated at 60 and 120 min. There was a statistically significant two-way interaction between treatment and time on serum Mg (p = 0.037). A difference of −0.085 mm in FMD was observed 60-min post drink in the control group, as compared to baseline FMD, and no difference was observed in the supplement group as compared to baseline. Despite the non-significant interaction between treatment and time on FMD, once adjusted for baseline, the difference seen in the control group and the lack of change in the supplement group at 60 min post-drink suggests that Mg might attenuate the reduction in FMD post-prandiall

Grüneisen parameter of hcp‐Fe to 171 GPa

We measured the phonon density of states (DOS) of hexagonal close-packed iron (ɛ-Fe) with high statistical quality using nuclear resonant inelastic X-ray scattering and in situ X-ray diffraction experiments between pressures of 30 GPa and 171 GPa and at 300 K, with a neon pressure medium up to 69 GPa. The shape of the phonon DOS remained similar at all compression points, while the maximum (cutoff) energy increased regularly with decreasing volume. As a result, we present a generalized scaling law to describe the volume dependence of ɛ-Fe's total phonon DOS which, in turn, is directly related to the ambient temperature vibrational Grüneisen parameter (γ_(vib)). Fitting our individual γ_(vib) data points with γ_(vib) = γ_(vib),0(V/V0)^q, a common parameterization, we found an ambient pressure γ_(vib,0) = 2.0 ± 0.1 for the range q = 0.8 to 1.2. We also determined the Debye sound velocity (v_D) from the low-energy region of the phonon DOS and our in situ measured volumes, and used the volume dependence of v_D to determine the commonly discussed Debye Grüneisen parameter (γ_D). Comparing our γ_(vib)(V) and γ_D(V), we found γ_(vib) to be ∼10% larger than γ_D at any given volume. Finally, applying our γ_(vib)(V) to a Mie-Grüneisen type relationship and an approximate form of the empirical Lindemann melting criterion, we predict the vibrational thermal pressure and estimate the high-pressure melting behavior of ɛ-Fe at Earth's core pressures

Evaluating Otter Reintroduction Outcomes Using Genetic Spatial Capture-Recapture Modified for Dendritic Networks

Monitoring the demographics and genetics of reintroduced populations is critical to evaluating reintroduction success, but species ecology and the landscapes that they inhabit often present challenges for accurate assessments. If suitable habitats are restricted to hierarchical dendritic networks, such as river systems, animal movements are typically constrained and may violate assumptions of methods commonly used to estimate demographic parameters. Using genetic detection data collected via fecal sampling at latrines, we demonstrate applicability of the spatial capture–recapture (SCR) network distance function for estimating the size and density of a recently reintroduced North American river otter (Lontra canadensis) population in the Upper Rio Grande River dendritic network in the southwestern United States, and we also evaluated the genetic outcomes of using a small founder group (n = 33 otters) for reintroduction. Estimated population density was 0.23–0.28 otter/km, or 1 otter/3.57–4.35 km, with weak evidence of density increasing with northerly latitude (β = 0.33). Estimated population size was 83–104 total otters in 359 km of riverine dendritic network, which corresponded to average annual exponential population growth of 1.12–1.15/year since reintroduction. Growth was ≥40% lower than most reintroduced river otter populations and strong evidence of a founder effect existed 8–10 years post-reintroduction, including 13–21% genetic diversity loss, 84%–87% genetic effective population size decline, and rapid divergence from the source population (FST accumulation = 0.06/generation). Consequently, genetic restoration via translocation of additional otters from other populations may be necessary to mitigate deleterious genetic effects in this small, isolated population. Combined with non-invasive genetic sampling, the SCR network distance approach is likely widely applicable to demogenetic assessments of both reintroduced and established populations of multiple mustelid species that inhabit aquatic dendritic networks, many of which are regionally or globally imperiled and may warrant reintroduction or augmentation efforts

Benefits of Real-Time Continuous Glucose Monitoring in Pregnancy

In recent years, continuous glucose monitoring (CGM) has become increasingly available with the introduction of devices that are specifically approved for use during pregnancy. Evidence in the form of randomized-controlled trials and cohort studies continues to build support for the use of CGM during pregnancy to improve measures of maternal glycemia as well as obstetric and neonatal outcomes. Based on data from the CGM in pregnant women with type 1 diabetes (CONCEPTT) trial alongside a Swedish cohort study of real-world outcomes of pregnant women with type 1 diabetes, the UK National Institute for Health and Clinical Excellence (NICE) guidelines now recommend that real-time CGM be offered to all pregnant women with type 1 diabetes. Based on these guidelines, all pregnant individuals in the United Kingdom with type 1 diabetes will receive government-funded real-time CGM for a 12-month duration. These guidelines are a game-changer and will continue to facilitate more widespread access to CGM use in the United Kingdom and beyond. This review describes the role of CGM in the management of diabetes in pregnancy, discusses contemporary maternal glucose levels and their relationship with outcomes in diabetes pregnancies, and examines the high-quality, randomized-controlled trial and the real-world clinical data evaluating the impact of CGM use

Biases in Long-term NO2 Averages Inferred from Satellite Observations Due to Cloud Selection Criteria

Retrievals of atmospheric trace gas column densities from space are compromised by the presence of clouds, requiring most studies to exclude observations with significant cloud fractions in the instrument's field of view. Using NO2 observations at three ground stations representing urban, suburban, and rural environments, and tropospheric vertical column densities measured by the Ozone Monitoring Instrument (OMI) over each site, we show that the observations from space represent monthly averaged ground-level pollutant conditions well (R=0.86) under relatively cloud-free conditions. However, by analyzing the ground-level data and applying the OMI cloud fraction as a filter, we show there is a significant bias in long-term averaged NO2 as a result of removing the data during cloudy conditions. For the ground-based sites considered in this study, excluding observations on days when OMI-derived cloud fractions were greater than 0.2 causes 12:00-14:00 mean summer mixing ratios to be underestimated by 12%+/-6%, 20%+/-7%, and 40%+/-10% on average (+/-1 standard deviation) at the urban, suburban, and rural sites respectively. This bias was investigated in particular at the rural site, a region where pollutant transport is the main source of NO2, and where longterm observations of NOy were also available. Evidence of changing photochemical conditions and a correlation between clear skies and the transport of cleaner air masses play key roles in explaining the bias. The magnitude of a bias is expected to vary from site to site depending on meteorology and proximity to NOx sources, and decreases when longer averaging times of ground station data (e.g. 24-h) are used for the comparison

Estimating the stability of heartbeat counting in middle childhood: a twin study

There is growing interest in interoception, the perception of the body’s internal state, and its relevance for health across development. Most evidence linking interoception to health has used the heartbeat counting task. However, the temporal stability of the measure, particularly during childhood, and the etiological factors that underlie stability, remain largely unexamined. Using data from the ECHO twin sample we estimated the magnitude of genetic and environmental influences on the stability of heartbeat counting across two years (age 8-10), the longest timeframe examined. Heartbeat counting accuracy was modestly correlated across time, (r=.35), and accuracy improved with age. Non-shared environmental factors accounted for the most variance at both time points and were the main contributors to temporal stability of heartbeat counting. Future research should seek to identify these non-shared environmental factors and elucidate whether this relatively modest stability reflects variability of interoception across development or unreliability of the heartbeat counting task