With multidrug resistant bacteria on the rise, new antibiotic approaches are required. Although a number of new small molecule antibiotics are currently in the development pipeline with many more in ...preclinical development, the clinical options and practices for infection control must be expanded. Biologics and non-antibiotic adjuvants offer this opportunity for expansion. Nevertheless, to avoid known mechanisms of resistance, intelligent combination approaches for multiple simultaneous and complimentary therapies must be designed. Combination approaches should extend beyond biologically active molecules to include smart controlled delivery strategies. Infection control must integrate antimicrobial stewardship, new antibiotic molecules, biologics, and delivery strategies into effective combination therapies designed to 1) fight the infection, 2) avoid resistance, and 3) protect the natural microbiome. This review explores these developing strategies in the context of circumventing current mechanisms of resistance.
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We describe results from a new technique for the prediction of complete, self-consistent X-ray spectra from three-dimensional general relativistic magnetohydrodynamic (GRMHD) simulations of black ...hole accretion flows. Density and cooling rate data from a harm3d GRMHD simulation are post-processed by an improved version of the Monte Carlo radiation transport code pandurata (in the corona) and the Feautrier solver ptransx (in the disk), with xstar subroutines. The codes are run in a sequential, iterative fashion to achieve globally energy-conserving and self-consistent radiation fields, temperature maps, and photoionization equilibria. The output is the X-ray spectrum as seen by a distant observer, including features, such as the Fe K emission line and corresponding K-edge absorption trough, due to disk reprocessing of coronal power. For the example cases we consider-a non-rotating 10 M black hole with solar abundances, accreting at 0.01, 0.03, 0.1, or 0.3 Eddington-we find spectra resembling actual observations of stellar-mass black holes in the soft or steep power-law state: broad thermal peaks (at 1-3 keV), steep power laws extending to high energy (Γ = 2.7-4.5), and prominent, asymmetric Fe K emission lines with equivalent widths in the range 40-400 eV (larger EW at lower accretion rates). By starting with simulation data, we obviate the need for parameterized descriptions of the accretion flow geometry-no a priori specification of the corona's shape or flux, or the disk temperature or density, etc., is needed. Instead, we apply the relevant physical principles to simulation output using appropriate numerical techniques; this procedure allows us to calculate inclination-dependent spectra after choosing only a small number of physically meaningful parameters: black hole mass and spin, accretion rate, and elemental abundances.
School-based physical activity and running programmes, such as The Daily Mile™, are increasing in popularity globally. The aim of this research was to examine the acute impact of such classroom ...physical activity breaks on cognition and affective wellbeing.
A total of 5463 school pupils from 332 schools took part in a citizen science project with a repeated measures design. They completed tasks of cognition (inhibition, verbal, and visuo-spatial working memory) and the Children's Feeling Scale and Felt Arousal Scale before and after three different outdoor activities: a classroom break of 15 min of self-paced activity, a near maximal exhaustion activity (the bleep test), and a no-exercise control group where pupils sat or stood outside. Wellbeing and fitness were examined as mediators of the relationship between outdoor activity and cognition.
Fifteen minutes of self-paced outdoor activity was beneficial for pupils' cognition and wellbeing in comparison to both other activities (Cohen's d effect sizes ranging from 0.04 to 0.22; small). The relationship with cognition was not mediated by participants' fitness level and was only partially mediated by wellbeing. Change scores for alertness were higher after the bleep test compared to the control activity but similar for all other outcomes.
Taking a break from the classroom to complete 15 min of self-paced physical activity should be considered a worthwhile activity by class teachers, school management, and policymakers. Additionally, more intense physical activity should not be considered to be detrimental.
N-Heterocyclic carbenes catalyze the oxidation of allylic, propargylic, and benzylic alcohols to esters with manganese(IV) oxide in excellent yields. A variety of ester derivatives can be ...synthesized, including protected carboxylates. This one-pot tandem oxidation represents the first organocatalytic oxidation of alcohols to esters. Saturated esters can also be accessed from aldehydes using this method. Through the utilization of a chiral catalyst, the acyl−heteroazolium intermediate becomes a chiral acylating agent, which can desymmetrize meso-1,2-diols.
Taste and smell play a key role in our ability to perceive foods. Overconsumption of highly palatable energy-dense foods can lead to increased caloric intake and obesity. Thus there is growing ...interest in the study of the biological mediators of fat taste and associated olfaction as potential targets for pharmacologic and nutritional interventions in the context of obesity and health. The number of studies examining mechanisms underlying fat taste and smell has grown rapidly in the last 5 years. Therefore, the purpose of this systematic review is to summarize emerging evidence examining the biological mechanisms of fat taste and smell. A literature search was conducted of studies published in English between 2014 and 2021 in adult humans and animal models. Database searches were conducted using PubMed, EMBASE, Scopus, and Web of Science for key terms including fat/lipid, taste, and olfaction. Initially, 4,062 articles were identified through database searches, and a total of 84 relevant articles met inclusion and exclusion criteria and are included in this review. Existing literature suggests that there are several proteins integral to fat chemosensation, including cluster of differentiation 36 (CD36) and G protein-coupled receptor 120 (GPR120). This systematic review will discuss these proteins and the signal transduction pathways involved in fat detection. We also review neural circuits, key brain regions, ingestive cues, postingestive signals, and genetic polymorphism that play a role in fat perception and consumption. Finally, we discuss the role of fat taste and smell in the context of eating behavior and obesity.
How should ecologists and evolutionary biologists analyze nonnormal data that involve random effects? Nonnormal data such as counts or proportions often defy classical statistical procedures. ...Generalized linear mixed models (GLMMs) provide a more flexible approach for analyzing nonnormal data when random effects are present. The explosion of research on GLMMs in the last decade has generated considerable uncertainty for practitioners in ecology and evolution. Despite the availability of accurate techniques for estimating GLMM parameters in simple cases, complex GLMMs are challenging to fit and statistical inference such as hypothesis testing remains difficult. We review the use (and misuse) of GLMMs in ecology and evolution, discuss estimation and inference and summarize ‘best-practice’ data analysis procedures for scientists facing this challenge.
Single-cell technologies (RNA-sequencing, flow cytometry) are critical tools to reveal how cell heterogeneity impacts developmental pathways. The placenta is a fetal exchange organ, containing a ...heterogeneous mix of mesenchymal cells (fibroblasts, myofibroblasts, perivascular, and progenitor cells). Placental mesenchymal stromal cells (pMSC) are also routinely isolated, for therapeutic and research purposes. However, our understanding of the diverse phenotypes of placental mesenchymal lineages, and their relationships remain unclear. We designed a 23-colour flow cytometry panel to assess mesenchymal heterogeneity in first-trimester human placentae. Four distinct mesenchymal subsets were identified; CD73
+
CD90
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mesenchymal cells, CD146
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CD271
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perivascular cells, podoplanin
+
CD36
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stromal cells, and CD26
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CD90
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myofibroblasts. CD73
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CD90
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and podoplanin + CD36+ cells expressed markers consistent with cultured pMSCs, and were explored further. Despite their distinct ex-vivo phenotype, in culture CD73
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CD90
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cells and podoplanin
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CD36
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cells underwent phenotypic convergence, losing CD271 or CD36 expression respectively, and homogenously exhibiting a basic MSC phenotype (CD73
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CD90
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CD31
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CD144
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CD45
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). However, some markers (CD26, CD146) were not impacted, or differentially impacted by culture in different populations. Comparisons of cultured phenotypes to pMSCs further suggested cultured pMSCs originate from podoplanin
+
CD36
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cells. This highlights the importance of detailed cell phenotyping to optimise therapeutic capacity, and ensure use of relevant cells in functional assays.
Abstract
Globally, thunderstorms are responsible for a significant fraction of rainfall, and in the mid-latitudes often produce extreme weather, including large hail, tornadoes and damaging winds. ...Despite this importance, how the global frequency of thunderstorms and their accompanying hazards has changed over the past 4 decades remains unclear. Large-scale diagnostics applied to global climate models have suggested that the frequency of thunderstorms and their intensity is likely to increase in the future. Here, we show that according to ERA5 convective available potential energy (CAPE) and convective precipitation (CP) have decreased over the tropics and subtropics with simultaneous increases in 0–6 km wind shear (BS06). Conversely, rawinsonde observations paint a different picture across the mid-latitudes with increasing CAPE and significant decreases to BS06. Differing trends and disagreement between ERA5 and rawinsondes observed over some regions suggest that results should be interpreted with caution, especially for CAPE and CP across tropics where uncertainty is the highest and reliable long-term rawinsonde observations are missing.
The oral microbiome is incredibly complex, containing a diverse complement of microbiota that has previously been categorized into 6 broad phyla. While techniques such as next-generation sequencing ...have contributed to a better understanding of the composition of the oral microbiome, the role it plays in human health and disease is still under investigation. Previous studies have identified that a more diverse microbiome is advantageous for health. Therefore, alterations to the physical or mental health that are of interest in this study, such as stress, are the factors that decrease microbial diversity, leading to the potential for dysbiosis and disease disposition. Intensive Surgical Skills Week (ISSW) is a hyper-realistic simulation training week for military medical students that takes place at the Strategic Operations (STOPS) facility in San Diego, CA. This training week puts students through mass causality simulations and requires them to work through distinct roles within the healthcare team, providing an almost ideal environment to assess the impact of acute stress on oral microbiome diversity. Based on the literature on stress and microbiota, we hypothesized that the high stress simulation events at ISSW will impact the composition and diversity of the oral microbiome.
To investigate this hypothesis, thirty-seven (
= 37) second-or third-year medical students who are enlisted in a branch of the military and who attended ISSW in July of 2021 were included in the study. Student participants were divided into 7 teams to complete the hyper-realistic simulations (SIMs) at ISSW. A pilot of sixty-four buccal samples (
= 64) from three of the seven teams were sent for analysis at the University of Missouri Metagenomic Center.
We saw an overall increase in species richness at the end of ISSW when looking at all samples (
= 64). Fourteen significantly different bacteria were identified from the beginning to the end of data collection. Additionally, third year medical students appear to have a greater species richness compared to second year medical students. Further, third year medical students had a statically significant difference in their oral microbiome richness from beginning to end of data collection (
= 0.008).
Our preliminary data indicates that physical and psychological stress can impact the composition of the oral microbiome. The analyses in this study show that using the oral microbiome as an indicator of stress is promising and may provide evidence to support stress management practices.
The Jovian flywheel model was developed to explain the remarkable steadiness of the observed corotation lag in Jupiter's magnetosphere. The key conclusion of that research was that the observed lag ...is primarily due to slippage within the neutral atmosphere, with only a small fraction of it arising from slippage between the thermosphere and magnetosphere. Moreover, the neutral wind profile in the atmosphere responds very slowly, so it acts as a mechanical flywheel to dampen out temporal variations with timescales less than several months. We adapt the model for Saturn by allowing the Pedersen conductance to differ in the northern and southern hemispheres. In steady state, the two neutral thermospheres then have different rotation rates that can slowly vary with the season on Saturn as solar illumination of the poles varies.
Plain Language Summary
The time for Saturn to rotate once is difficult to measure from Earth. For many questions, the key is the magnetic field's rotation period, which is fixed to the planet's core. Voyager measured regular variations in the magnetic field and radio waves that implied a rotation period of 10 hr, 40 min, which was accepted as Saturn's period for over two decades. When Cassini arrived, the rotation period was 10 min longer and slowly varied over the next 13 years. Additional data showed that the north and south hemispheres actually have different varying slowly periods. We propose an explanation. As charged particles move through Saturn's magnetic field (its “magnetosphere”), they change rotational speed, just as ballet dancers change speed by shifting their limbs. This puts electromagnetic stress on the planet's atmosphere and causes a high‐altitude layer to rotate more slowly. The summer hemisphere is more directly exposed to solar ultraviolet radiation, which makes it conduct electricity better. Electrical currents go preferentially to that hemisphere, which slows the atmosphere more than in the winter hemisphere. The result is a longer summer period compared to the winter. As the seasons change, the rotation periods should swap between North and South, as is observed.
Key Points
Seasonal ionospheric conductivity variations cause magnetospheric plasma dynamics to exert unequal torques on Saturn's neutral atmosphere
The northern and southern thermospheres acquire unequal rotation periods that vary slowly because of their very large moments of inertia
Effects of ionosphere‐thermosphere coupling can show simultaneous, unequal periods, thus explaining the observed variable dual periodicity
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