Recent advances in stable isotope measurements now allow for detailed investigations of the sources, transformations, and deposition of reactive nitrogen (N) species. Stable isotopes show promise as ...a complementary tool for apportioning emissions sources that contribute to deposition and also for developing a more robust understanding of the transformations that can influence these isotope ratios. Methodological advances have facilitated the unprecedented examination of the isotopic composition of reactive N species in the atmosphere and in precipitation including nitrogen oxides (NOx = nitric oxide (NO) + nitrogen dioxide (NO2)), atmospheric nitrate (NO3−), nitric acid (HNO3), ammonia (NH3), and ammonium (NH4+). This isotopic information provides new insight into the mechanisms of transformation and cycling of reactive N in the atmosphere and moreover helps resolve the contribution of multiple NOx and NH3 emission sources to deposition across landscapes, regions, and continents. Here, we highlight the current state of knowledge regarding the isotopic ratios of NOx and NH3 emission sources and chemical alterations of isotopic ratios during atmospheric transformations. We also highlight illustrative examples where isotopic approaches are used and review recent methodological advances. While these highlights are not an exhaustive review of the literature, we hope they provide a glimpse of the potential for these methods to help resolve knowledge gaps regarding total N deposition to Earth surfaces. We conclude with promising opportunities for future research in the short-, medium-, and long-term.
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•Isotopes of reactive nitrogen species can aid in understanding emissions sources and chemical transformations that contribute to reactive nitrogen deposition.•Methodological advances have ushered in an unprecedented examination of reactive nitrogen isotope chemistry.•Here, we review advances in methods, applications, and gains in knowledge during the past decade.•We conclude with promising opportunities for future research in the short, medium-, and long-term.
High-producing Holstein Friesian dairy cattle have a characteristic black and white coat, often with large proportions of black. Compared to a light coat color, black absorbs more solar radiation ...which is a contributing factor to heat stress in cattle. To better adapt dairy cattle to rapidly warming climates, we aimed to lighten their coat color by genome editing.
Using gRNA/Cas9-mediated editing, we introduced a three bp deletion in the pre-melanosomal protein 17 gene (PMEL) proposed as causative variant for the semi-dominant color dilution phenotype observed in Galloway and Highland cattle. Calves generated from cells with homozygous edits revealed a strong color dilution effect. Instead of the characteristic black and white markings of control calves generated from unedited cells, the edited calves displayed a novel grey and white coat pattern.
This, for the first time, verified the causative nature of the PMEL mutation for diluting the black coat color in cattle. Although only one of the calves was healthy at birth and later succumbed to a naval infection, the study showed the feasibility of generating such edited animals with the possibility to dissect the effects of the introgressed edit and other interfering allelic variants that might exist in individual cattle and accurately determine the impact of only the three bp change.
Nursing students in a community health course implemented a quality improvement project with active older adults (AOA). This article describes a process for transitioning an in-person community ...health quality improvement (QI) project to online.
To communicate with AOA, students created a blog, "Healthy Living From Home," that enabled communication among the AOA, partner organizations staff, and students. A quick response code was created that linked to the 6-week program. At the end of the 6 weeks, participants were asked to complete a survey.
Data collected from the QI project website tracked more than 1,000 visits to the blog. Participants rated project enjoyment, helpfulness, and educational content as 4.5 on a 5-point Likert scale.
Using a multifocal online format to engage with AOA was successful and can continue to be used in the future.
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Physiologically based pharmacokinetic (PBPK) modeling is a valuable tool in drug development and regulatory assessment, as it offers the opportunity to simulate the pharmacokinetics of a compound, ...with a mechanistic understanding, in a variety of populations and situations. This work reviews the use and impact of such modeling in selected regulatory procedures submitted to the European Medicines Agency (EMA) before the end of 2015, together with its subsequent reflection in public documents relating to the assessment of these procedures. It is apparent that the reference to PBPK modeling in regulatory public documents underrepresents its use. A positive trend over time of the number of PBPK models submitted is shown, and in a number of cases the results of these may impact the decision‐making process or lead to recommendations in the product labeling. These results confirm the need for regulatory guidance in this field, which is currently under development by the EMA.
The notion that family support may buffer individuals under adversity from poor outcomes has been theorized to have important implications for mental and physical health, but little is known about ...the biological mechanisms that explain these links. We hypothesized that adults who grew up in low socioeconomic status (SES) households but who experienced high levels of maternal warmth would be protected from the pro-inflammatory states typically associated with low SES. A total of 53 healthy adults (aged 25-40 years) low in SES early in life were assessed on markers of immune activation and systemic inflammation. Genome-wide transcriptional profiling also was conducted. Low early-life SES individuals who had mothers, who expressed high warmth toward them, exhibited less Toll-like receptor-stimulated production of interleukin 6, and reduced bioinformatic indications of pro-inflammatory transcription factor activity (NF-κB) and immune activating transcription factor activity (AP-1) compared to those who were low in SES early in life but experienced low maternal warmth. To the extent that such effects are causal, they suggest the possibility that the detrimental immunologic effects of low early-life SES environments may be partly diminished through supportive family climates.
We examine the effect of (in)congruence between leaders' and teams' power distance values on team effectiveness. We hypothesize that the (in)congruence between these values would differentially ...predict team effectiveness, with procedural justice climate serving as a mediator. Using multisource data and polynomial regression, we found that similarities (and differences) between leaders' and their teams' power distance values can have consequential effects on teams' justice climate and, ultimately, their effectiveness (viz., team performance and team organizational citizenship behavior). We conclude that to fully understand the implications of power distance, one should consider the multiple perspectives of both leaders and team members.
Heart failure with preserved ejection fraction (HFpEF) is a common syndrome with a pressing shortage of therapies. Exercise intolerance is a cardinal symptom of HFpEF, yet its pathophysiology remains ...uncertain.
We investigated the mechanism of exercise intolerance in 134 patients referred for cardiopulmonary exercise testing: 79 with HFpEF and 55 controls. We performed cardiopulmonary exercise testing with invasive monitoring to measure hemodynamics, blood gases, and gas exchange during exercise. We used these measurements to quantify 6 steps of oxygen transport and utilization (the O
pathway) in each patient with HFpEF, identifying the defective steps that impair each one's exercise capacity (peak Vo
). We then quantified the functional significance of each O
pathway defect by calculating the improvement in exercise capacity a patient could expect from correcting the defect.
Peak Vo
was reduced by 34±2% (mean±SEM,
<0.001) in HFpEF compared with controls of similar age, sex, and body mass index. The vast majority (97%) of patients with HFpEF harbored defects at multiple steps of the O
pathway, the identity and magnitude of which varied widely. Two of these steps, cardiac output and skeletal muscle O
diffusion, were impaired relative to controls by an average of 27±3% and 36±2%, respectively (
<0.001 for both). Due to interactions between a given patient's defects, the predicted benefit of correcting any single one was often minor; on average, correcting a patient's cardiac output led to a 7±0.5% predicted improvement in exercise intolerance, whereas correcting a patient's muscle diffusion capacity led to a 27±1% improvement. At the individual level, the impact of any given O
pathway defect on a patient's exercise capacity was strongly influenced by comorbid defects.
Systematic analysis of the O
pathway in HFpEF showed that exercise capacity was undermined by multiple defects, including reductions in cardiac output and skeletal muscle diffusion capacity. An important source of disease heterogeneity stemmed from variation in each patient's personal profile of defects. Personalized O
pathway analysis could identify patients most likely to benefit from treating a specific defect; however, the system properties of O
transport favor treating multiple defects at once, as with exercise training.
With the recent achievement of extremely high-quality epitaxial interfaces between InAs nanowires and superconducting Al shells with strong superconductor-semiconductor tunnel coupling, a new regime ...of proximity-induced superconductivity in semiconductors can be explored where the induced gap may be similar in value to the bulk Al gap (large gap) with negligible subgap conductance (hard gap). We propose several experimentally relevant consequences of this large-gap strong-coupling regime for tunneling experiments, and we comment on the prospects of this regime for topological superconductivity. In particular, we show that the advantages of having a strong spin-orbit coupling and a large spin g factor in the semiconductor nanowire may both be compromised in this strongly coupled limit, and somewhat weaker interface tunneling may be necessary for achieving optimal proximity superconductivity in the semiconductor nanowire. We derive a minimal, generic theory for the strong-coupling hard-gap regime obtaining good qualitative agreement with the experiment and pointing out future directions for further progress toward Majorana nanowires in hybrid semiconductor-superconductor structures.
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