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The width of the Inter-Tropical Convergence Zone (ITCZ) affects tropical rainfall, Earth's albedo, large-scale circulation, and climate sensitivity. To better understand the ITCZ width and its effects on global climate, we present a protocol to force changes in ITCZ width in climate models. Starting from an aquaplanet configuration with a slab ocean, adding surface heat fluxes in the deep tropics forces the ITCZ to narrow, and subtracting them causes it to widen. The protocol successfully generates changes in ITCZ width in all four climate models used in this study. ITCZ width in each model responds linearly to forcing magnitude and sign. Comparing across the four climate models, a response to varying ITCZ width that is remarkably consistent among models is the ITCZ strength, which is greater the narrower the ITCZ. On the other hand, the effect of varying ITCZ width on climate sensitivity is divergent among our four models, varying even in sign. Results from this pilot study highlight the connections between surface fluxes, ITCZ width, and the wider climate. A comprehensive model intercomparison project (MIP) has the potential to advance understanding of both the physical processes shaping ITCZ width and its influence on remote atmospheric circulations and global climate. [ABSTRACT FROM AUTHOR]

Monsoon depressions (MDs) are synoptic‐scale storms that occur during the summer phase of the global monsoon cycle and whose dynamical mechanisms remain incompletely understood. To gain insight into the dynamics governing the large‐scale structure of MDs, we formulate an idealised moist‐thermal quasi‐geostrophic model that includes distinct thermal and moisture fields in simple forms. A linear‐stability analysis of the model, with basic states corresponding to typical monsoon conditions, shows three distinct mode classifications: thermal‐Rossby modes, heavy precipitating modes, and a moist‐thermal mode. In the linearised model, the presence of a background precipitation gradient strengthens thermal‐Rossby modes by coupling the dynamics to latent heating. The separation of heavy precipitating modes from fast‐propagating thermal‐Rossby modes is further examined with numerical experiments of large‐amplitude MDs. Wind‐induced evaporation is found to amplify large‐amplitude MDs in conditions analogous to those over the northern Bay of Bengal. An energetic analysis shows the pathways by which the MDs derive energy from the background state. A further series of experiments through a continuum of meridional temperature gradients demonstrates the sensitivity of large‐scale MD dynamics to the background state and suggests a possible mechanism to explain variations in the propagation direction of MDs. [ABSTRACT FROM AUTHOR]

We analyse the real part of one-loop five-parton amplitudes in the next-to-multi-Regge kinematic (NMRK) limit, to leading power, and to finite order in the dimensional regularisation parameter. To leading logarithmic (LL) accuracy, it is known that five-parton amplitudes in this limit are given to all-orders by a single factorised expression, in which the pair of partons which are not well-separated in rapidity are described by a two-parton emission vertex. In this study, we investigate the one-loop amplitudes at next-to-leading logarithmic (NLL) accuracy, and find that is has a more complex structure. In particular, it is found that the purely gluonic amplitudes are compatible with an analogous factorisation of individual colour structures. From the one-loop amplitudes we extract one-loop two-parton emission vertices, which are functions of a subset of the momenta of the amplitude. In the multi-Regge kinematic (MRK) limit, the vertices themselves factorise into the known one-loop single-parton emission vertices and Lipatov vertex, with rapidity dependence governed by the one-loop gluon Regge trajectory, as required by compatibility with the known MRK limit of amplitudes. The one-loop two-parton emission vertices are necessary ingredients for the construction of the next-to-next-to leading order (NNLO) jet impact factors in the BFKL framework. [ABSTRACT FROM AUTHOR]

This paper examines the impact of climate risk on macroeconomic activity for thirty countries using over a century of panel time series data. The key innovation of our paper is to use a factor stochastic volatility approach to decompose climate change into global and country-specific climate risk and to consider their distinct impact upon macroeconomic activity. To allow for country heterogeneity, we also differentiate the impact of climate risk upon advanced and emerging economies. While the existing literature has focused on country based climate risk shocks, our results suggest idiosyncratic or country-specific climate risk shocks are relatively unimportant. Global climate risk, on the other hand, has a negative and relatively more important impact on macroeconomic activity. In particular, we find that both advanced and emerging countries are adversely impacted by global climate risk shocks. [ABSTRACT FROM AUTHOR]

The width of the ITCZ affects tropical rainfall, Earth's albedo, large-scale circulation and climate sensitivity; yet we do not understand what controls it. To better understand the ITCZ width and its effects on global climate, we present a protocol to force changes in ITCZ width in climate models. Starting from an aquaplanet configuration with a slab ocean, adding surface heat fluxes in the deep tropics forces the ITCZ to narrow, and subtracting them causes it to widen. The protocol successfully generates changes in ITCZ width in four climate models; within each model, ITCZ width responds linearly to forcing magnitude and sign. Comparing across the four climate models, a response to varying ITCZ width that is remarkably consistent among models is the ITCZ strength, which is greater the narrower the ITCZ. On the other hand, the effect of varying ITCZ width on climate sensitivity is divergent among our four models, varying even in sign. These results indicate that idealized model experiments have the potential to increase our understanding of ITCZ width. [ABSTRACT FROM AUTHOR]

One of the limiting factors to developing plasma thrusters on alternative propellants is the cost associated with changing the diagnostic tools, which are often propellant-dependent. For laser induced fluorescence (LIF), which is typically used for ion velocity distribution measurements to determine ion trajectories and potential profiles, either new lasers need to be bought, which are tuned to the wavelength of the new element's excitation level, or a costly tunable laser is required. A method to use existing LIF setups designed for xenon on any propellant has been demonstrated on a Hall thruster operating on krypton. In the demonstration test, a small amount of xenon (0.01%–4%) was mixed with the main krypton propellant for use as a diagnostic tracer, and xenon ion velocities were measured while also monitoring changes in the mean discharge current and oscillations. High signal-to-noise ratios in LIF data acquired along the channel centerline were obtained with tracer gas fractions ≤1% that negligibly affected the thruster operation. These results and comparison of the emission spectra of xenon and other common propellants suggest that the tracer LIF method should be broadly applicable to LIF measurements in Hall thrusters operating on alternative propellants. [ABSTRACT FROM AUTHOR]

Observational data and numerical models suggest that, under climate change, elevated and non-elevated land surfaces warm at different rates. Proposed drivers of this 'elevation-dependent warming' (EDW) include surface albedo and water vapour feedbacks, the temperature dependence of longwave emission, and aerosols. Yet the relative importance of each proposed mechanism both regionally and at large scales is unclear, highlighting an incomplete physical understanding of EDW. Here we use gridded observations, atmospheric reanalysis, and a range of climate model simulations to investigate EDW over the historical period across the tropics and subtropics (40° S to 40° N). Observations, reanalysis, and fully-coupled models exhibit annual-mean warming trends (1959–2014), binned by surface elevation, that are larger over elevated surfaces and broadly consistent across datasets. EDW varies by season, with stronger observed signals in boreal autumn and winter. Analysis of large ensembles of single-forcing simulations (1959–2005) suggests historical EDW is likely a forced response of the climate system rather than an artefact of internal variability, and is primarily driven by increasing greenhouse gas concentrations. To gain quantitative insight into the mechanisms contributing to large-scale EDW, a forcing/feedback framework based on top-of-atmosphere energy balance is applied to the fully-coupled models. This framework identifies the Planck and surface albedo feedbacks as being robust drivers of EDW (i.e., enhancing warming over elevated surfaces), with energy transport by the atmospheric circulation also playing an important role. In contrast, water vapour and cloud feedbacks along with weaker radiative forcing in elevated regions oppose EDW. Implications of the results for understanding future EDW are discussed. [ABSTRACT FROM AUTHOR]

A key implication of the well known wet‐get‐wetter/dry‐get‐drier (WGW) scaling is that model biases in the representation of precipitation and evaporation in the present climate lead to spurious projected changes under global warming. Here we estimate the extent of such spurious changes in projections by 60 models participating in phases 5 and 6 of the Coupled Model Intercomparison Project. Utilizing known thermodynamic constraints on evaporation, we show that the WGW scaling can be applied to precipitation and evaporation separately (specific WGW scaling), which we use to correct for spurious projected changes in precipitation and evaporation over tropical oceans. The spurious changes in precipitation can be of comparable amplitude to projected changes, but are generally small for evaporation. The spurious changes may increase the uncertainty in projections of tropical precipitation and evaporation by up to 30% and 15% respectively. Plain Language Summary: It is well established that if winds are assumed unchanged, the response of the hydrological cycle to global warming will follow the simple rule that wet regions get wetter and dry regions get drier. A key implication of this rule is that climate model errors in the representation of precipitation and evaporation in the present climate lead to artificial simulated responses in a warming climate. Here we show that this simple rule can be applied separately to precipitation and evaporation over tropical oceans. We then use this rule to estimate the extent of the artificial response over tropical oceans to global warming in modern climate models, caused by errors in the representation of precipitation and evaporation. Overall, the artificial changes may increase the uncertainty in projections by up to 30% for precipitation and 15% for evaporation. Key Points: Biases in the representation of the present hydroclimate lead to spurious but correctable projected changes in precipitation and evaporationA wet‐get‐wetter/dry‐get‐drier scaling bias adjustment can be applied separately to precipitation and evaporationThe spurious changes increase uncertainty in precipitation and evaporation projections by up to 30% and 15% respectively [ABSTRACT FROM AUTHOR]

The 540s, 1450s, and 1600s represent three of the five coldest decades in the Common Era (CE). In each of these cases, the cause of these cold pulses has been attributed to large volcanic eruptions. However, the provenance of the eruption and magnitude of the volcanic forcing remains uncertain. Here, we use high-resolution sulfur isotopes in Greenland and Antarctic ice cores measured across these events to provide a means of improving sulfur loading estimates for these eruptions. In each case, the largest reconstructed tree-ring cooling is associated with an extratropical eruption, and the high-altitude stratospheric sulfate loading of these events is substantially smaller than previous estimates (by up to a factor of two). These results suggest an increased sensitivity of the reconstructed Northern Hemisphere summer temperature response to extratropical eruptions. This highlights the importance of climate feedbacks and processes that amplify and prolong the cooling signal from high latitudes, such as changes in sea ice extent and ocean heat content. [ABSTRACT FROM AUTHOR]

Horizontal temperature gradients in the tropical free troposphere are fairly weak, and tropical tropospheric warming is usually treated as uniform. However, we show here that projected tropospheric warming is spatially inhomogeneous in Coupled Model Intercomparison Project Phase 6 models, as well as in a storm‐resolving climate model. We relate the upper tropospheric warming pattern to sea‐surface temperature changes that reorganise convection and thereby cause spatial shifts in convective heating. Using the classical Gill model for tropical circulation and forcing it with precipitation changes that arise due to greenhouse gas warming, we can understand and reproduce the different warming patterns simulated by a range of global climate models. Forcing the Gill model with precipitation changes from a certain region demonstrates how local tropospheric temperature changes depend on local changes in convective heating. Close to the Equator, anomalous geopotential gradients are balanced by the dissipation term in the Gill model. The optimal dissipation time‐scale to reproduce the warming pattern varies depending on the Coupled Model Intercomparison Project Phase 6 model, and is between 1 and 10 days. We demonstrate that horizontal advection and eddy momentum fluxes have large enough equivalent dissipation time‐scales to balance the gradients in geopotential and thereby shape the warming pattern. Though climate models show a large spread in projections of tropical sea‐surface temperature and precipitation changes, our results imply that, once these predictions improve, our confidence in the predicted upper tropospheric warming pattern should also increase. [ABSTRACT FROM AUTHOR]

Grass uptake and phytoaccumulation factors of N-(n-butyl) thiophosphoric triamide (NBPT) and dicyandiamide (DCD) were quantified. Following the application of urea fertilizer treated with the inhibitors in Irish grassland, grass samples were collected at 5, 10, 15, 20, and 30 day time intervals following five application cycles. Uptake of NBPT by grass was below the limit of quantitation of the analytical method (0.010 mg NBPT kg-1). Dicyandiamide concentrations in grass ranged from 0.004 to 28 mg kg-1 with the highest concentrations measured on days 5 and 10. A reducing trend in concentration was found after day 15. The DCD phytoaccumulation factor was ranged from 0.004% to 1.1% showing that DCD can be taken up by grass at low levels when co-applied with granular urea. In contrast, NBPT was not detected indicating that grass uptake is unlikely when co-applied with granular urea fertilizer. The contrasting results are likely due to very different longevity of DCD and NBPT along with the much lower rate of NBPT, which is used compared with DCD. [ABSTRACT FROM AUTHOR]

Cloud feedbacks are the leading cause of uncertainty in climate sensitivity. The complex coupling between clouds and the large‐scale circulation in the tropics contributes to this uncertainty. To address this problem, the coupling between clouds and circulation in the latest generation of climate models is compared to observations. Significant biases are identified in the models. The implications of these biases are assessed by combining observations of the present day with future changes predicted by models to calculate observationally constrained feedbacks. For the dynamic cloud feedback (i.e., due to changes in circulation), the observationally constrained values are consistently larger than the model‐only values. This is due to models failing to capture a nonlinear minimum in cloud brightness for weakly descending regimes. Consequently, while the models consistently predict that these regimes increase in frequency in association with a weakening tropical circulation, they underestimate the positive cloud feedback associated with this increase. Plain Language Summary: Climate models are crucial for understanding the impacts of climate change. Yet there are significant differences between models even for the global mean temperature increase due to a doubling of carbon dioxide concentrations (known as the climate sensitivity). These differences in climate sensitivity are largely due to differences in cloud responses to warming between the models (known as cloud feedbacks). Cloud feedback uncertainty is particularly large for tropical clouds. One reason for this is the two‐way interactions between clouds and the large‐scale circulation. This remains relatively poorly understood and involves processes that occur at a wide range of scales which cannot be captured by climate models. This study examines relationships between clouds and circulation in the tropics in the latest generation of climate models. Cloud feedbacks can be separated into dynamic (changes in circulation) and thermodynamic (changes in cloud for a given circulation regime) components. We use this framework to calculate the cloud feedbacks models would predict if the relationships between clouds and circulation matched observations. This results in an increase in the dynamic component of the cloud feedback which is due to the models' failure to capture the observed nonlinear relationships between clouds and circulation. Key Points: Climate models miss key details of the observed links between tropical clouds and circulation, notably for common weak subsidence regimesUsing observations to constrain thermodynamic and dynamic cloud feedbacks in models increases the dynamic and hence total feedbackThis is due to subtle nonlinear changes in the observed SW cloud radiative effect across circulation regimes that the models predict will change in frequency [ABSTRACT FROM AUTHOR]

Electrical impedance tomography (EIT) is a non-invasive diagnostic tool for evaluating lung function. The objective of this study was to compare respiratory flow variables calculated from thoracic EIT measurements with corresponding spirometry variables. Ten healthy research horses were sedated and instrumented with spirometry via facemask and a single-plane EIT electrode belt around the thorax. Horses were exposed to sequentially increasing volumes of apparatus dead space between 1,000 and 8,500 mL, in 5–7 steps, to induce carbon dioxide rebreathing, until clinical hyperpnea or a tidal volume of 150% baseline was reached. A 2-min stabilization period followed by 2 minutes of data collection occurred at each timepoint. Peak inspiratory and expiratory flow, inspiratory and expiratory time, and expiratory nadir flow, defined as the lowest expiratory flow between the deceleration of flow of the first passive phase of expiration and the acceleration of flow of the second active phase of expiration were evaluated with EIT and spirometry. Breathing pattern was assessed based on the total impedance curve. Bland-Altman analysis was used to evaluate the agreement where perfect agreement was indicated by a ratio of EIT: spirometry of 1.0. The mean ratio (bias; expressed as a percentage difference from perfect agreement) and the 95% confidence interval of the bias are reported. There was good agreement between EIT-derived and spirometry-derived peak inspiratory [−15% (−46–32)] and expiratory [10% (−32–20)] flows and inspiratory [−6% (−25–18)] and expiratory [5% (−9–20)] times. Agreement for nadir flows was poor [−22% (−87–369)]. Sedated horses intermittently exhibited Cheyne-Stokes variant respiration, and a breath pattern with incomplete expiration in between breaths (crown-like breaths). Electrical impedance tomography can quantify airflow changes over increasing tidal volumes and changing breathing pattern when compared with spirometry in standing sedated horse. [ABSTRACT FROM AUTHOR]

Interactions of lectins with glycoconjugate-terbium(III) self-assembly complexes lead to sensing through enhanced lanthanide luminescence. This glycan-directed sensing paradigm detects an unlabelled lectin (LecA) associated with pathogen P. aeruginosa in solution, without any bactericidal activity. Further development of these probes could have potential as a diagnostic tool. [ABSTRACT FROM AUTHOR]

Cushing’s syndrome is an endocrine disorder caused by excess production of the stress hormone cortisol. Precision medicine strategies have identified single allele mutations within the PRKACA gene that drive adrenal Cushing’s syndrome. These mutations promote perturbations in the catalytic core of protein kinase A (PKAc) that impair autoinhibition by regulatory subunits and compartmentalization via recruitment into AKAP signaling islands. PKAcL205R is found in ∼45% of patients, whereas PKAcE31V, PKAcW196R, and L198insW and C199insV insertion mutants are less prevalent. Mass spectrometry, cellular, and biochemical data indicate that Cushing’s PKAc variants fall into two categories: those that interact with the heat-stable protein kinase inhibitor PKI, and those that do not. In vitro activity measurements show that wild-type PKAc and W196R activities are strongly inhibited by PKI (IC50 < 1 nM). In contrast, PKAcL205R activity is not blocked by the inhibitor. Immunofluorescent analyses show that the PKI-binding variants wild-type PKAc, E31V, and W196R are excluded from the nucleus and protected against proteolytic processing. Thermal stability measurements reveal that upon co-incubation with PKI and metal-bound nucleotide, the W196R variant tolerates melting temperatures 10°C higher than PKAcL205. Structural modeling maps PKI-interfering mutations to a ∼20 Å diameter area at the active site of the catalytic domain that interfaces with the pseudosubstrate of PKI. Thus, Cushing’s kinases are individually controlled, compartmentalized, and processed through their differential association with PKI. [ABSTRACT FROM AUTHOR]

Introduction: Trauma patients have diverse resource needs due to variable mechanisms and injury patterns. The aim of this study was to build a tool that uses only data available at time of admission to predict prolonged hospital length of stay (LOS). Methods: Data was collected from the trauma registry at an urban level one adult trauma center and included patients from 1/1/2014 to 3/31/2019. Trauma patients with one or fewer days LOS were excluded. Single layer and deep artificial neural networks were trained to identify patients in the top quartile of LOS and optimized on area under the receiver operator characteristic curve (AUROC). The predictive performance of the model was assessed on a separate test set using binary classification measures of accuracy, precision, and error. Results: 2953 admitted trauma patients with more than one-day LOS were included in this study. They were 70% male, 60% white, and averaged 47 years-old (SD: 21). 28% were penetrating trauma. Median length of stay was 5 days (IQR 3-9). For prediction of prolonged LOS, the deep neural network achieved an AUROC of 0.80 (95% CI: 0.786-0.814) specificity was 0.95, sensitivity was 0.32, with an overall accuracy of 0.79. Conclusion: Machine learning can predict, with excellent specificity, trauma patients who will have prolonged length of stay with only physiologic and demographic data available at the time of admission. These patients may benefit from additional resources with respect to disposition planning at the time of admission. [ABSTRACT FROM AUTHOR]

The chiral bis-tridentate (1,2,3-triazol-4-yl)-picolinamide (tzpa) ligand 1 was used in the formation of lanthanide di- and triple stranded di-metallic helicates in acetonitrile solution, where the changes in the ground and the Tb(III) excited state properties were used to monitor the formation of these supramolecular structures in situ under kinetic control. [ABSTRACT FROM AUTHOR]

Uncertainty in the response of clouds to global warming remains a significant barrier to reducing uncertainty in climate sensitivity. A key question is the extent to which the dynamic component—that which is due to changes in circulation rather than changes in the thermodynamic properties of clouds—contributes to the total cloud feedback. Here, simulations with a range of cloud‐resolving models are analyzed to quantify the impact of circulation changes on tropical cloud feedbacks. The dynamic component of the cloud feedback is substantial for some models and is controlled both by sea surface temperature (SST) induced changes in circulation and nonlinearity in the climatological relationship between clouds and circulation. We find notable inter‐model differences in the extent to which ascending regions narrow or expand in response to a change in SST, which we link to differences in the longwave and shortwave dynamic components across models. The diversity of changes in ascent area is coupled to intermodel differences in non‐radiative diabatic heating in ascending regions. Plain Language Summary: Clouds influence Earth's energy balance by absorbing and reflecting solar and terrestrial radiation. The response of clouds to warming remains a key source of uncertainty in understanding how the climate system will evolve. In particular, how the influence of clouds on radiation is coupled to the atmospheric circulation is an open question. In this study, idealized simulations of the tropics at high spatial resolution (3 km) are analyzed to probe how changes in circulation impact clouds in a warming climate. It is found that, across a range of models, the degree to which circulation changes influence clouds depends on how the area of the region with ascending air responds to warming. Key Points: Influence of circulation changes on cloud feedbacks is substantial in some cloud‐resolving modelsComponent of cloud feedback associated with circulation changes is coupled to ascent areaIntermodel spread in response of ascent area linked to non‐radiative diabatic heating [ABSTRACT FROM AUTHOR]

Innate or acquired resistance to small molecule BRAF or MEK1/2 inhibitors (BRAFi or MEKi) typically arises through mechanisms that sustain or reinstate ERK1/2 activation. This has led to the development of a range of ERK1/2 inhibitors (ERKi) that either inhibit kinase catalytic activity (catERKi) or additionally prevent the activating pT-E-pY dual phosphorylation of ERK1/2 by MEK1/2 (dual-mechanism or dmERKi). Here, we show that eight different ERKi (both catERKi or dmERKi) drive the turnover of ERK2, the most abundant ERK isoform, with little or no effect on ERK1. Thermal stability assays show that ERKi do not destabilise ERK2 (or ERK1) in vitro, suggesting that ERK2 turnover is a cellular consequence of ERKi binding. ERK2 turnover is not observed upon treatment with MEKi alone, suggesting it is ERKi binding to ERK2 that drives ERK2 turnover. However, MEKi pre-treatment, which blocks ERK2 pT-E-pY phosphorylation and dissociation from MEK1/2, prevents ERK2 turnover. ERKi treatment of cells drives the poly-ubiquitylation and proteasome-dependent turnover of ERK2 and pharmacological or genetic inhibition of Cullin-RING E3 ligases prevents this. Our results suggest that ERKi, including current clinical candidates, act as ‘kinase degraders’, driving the proteasome-dependent turnover of their major target, ERK2. This may be relevant to the suggestion of kinase-independent effects of ERK1/2 and the therapeutic use of ERKi. [ABSTRACT FROM AUTHOR]

Pseudokinases, so named because they lack one or more conserved canonical amino acids that define their catalytically active relatives, have evolved a variety of biological functions in both prokaryotic and eukaryotic organisms. Human PSKH2 is closely related to the canonical kinase PSKH1, which maps to the CAMK family of protein kinases. Primates encode PSKH2 in the form of a pseudokinase, which is predicted to be catalytically inactive due to loss of the invariant catalytic Asp residue. Although the biological role(s) of vertebrate PSKH2 proteins remains unclear, we previously identified specieslevel adaptions in PSKH2 that have led to the appearance of kinase or pseudokinase variants in vertebrate genomes alongside a canonical PSKH1 paralog. In this paper we confirm that, as predicted, PSKH2 lacks detectable protein phosphotransferase activity, and exploit structural informatics, biochemistry and cellular proteomics to begin to characterise vertebrate PSKH2 orthologues. AlphaFold 2-based structural analysis predicts functional roles for both the PSKH2 N- and C-regions that flank the pseudokinase domain core, and cellular truncation analysis confirms that the N-terminal domain, which contains a conserved myristoylation site, is required for both stable human PSKH2 expression and localisation to a membrane-rich subcellular fraction containing mitochondrial proteins. Using mass spectrometry-based proteomics, we confirm that human PSKH2 is part of a cellular mitochondrial protein network, and that its expression is regulated through client-status within the HSP90/Cdc37 molecular chaperone system. HSP90 interactions are mediated through binding to the PSKH2 C-terminal tail, leading us to predict that this region might act as both a cis and trans regulatory element, driving outputs linked to the PSKH2 pseudokinase domain that are important for functional signalling. [ABSTRACT FROM AUTHOR]

The yeast Komagataella phaffii (formerly called Pichia pastoris) is used widely as a host for secretion of heterologous proteins, but only a few isolates of this species exist and all the commonly used expression systems are derived from a single genetic background, CBS7435 (NRRL Y-11430). We hypothesized that other genetic backgrounds could harbor variants that affect yields of secreted proteins. We crossed CBS7435 with 2 other K. phaffii isolates and mapped quantitative trait loci (QTLs) for secretion of a heterologous protein, β-glucosidase, by sequencing individual segregant genomes. A major QTL mapped to a frameshift mutation in the mannosyltransferase gene HOC1, which gives CBS7435 a weaker cell wall and higher protein secretion than the other isolates. Inactivation of HOC1 in the other isolates doubled β-glucosidase secretion. A second QTL mapped to an amino acid substitution in IRA1 that tripled β-glucosidase secretion in 1-week batch cultures but reduced cell viability, and its effects are specific to this heterologous protein. Our results demonstrate that QTL analysis is a powerful method for dissecting the basis of biotechnological traits in nonconventional yeasts, and a route to improving their industrial performance. The yeast Komagataella phaffii (Pichia pastoris) is widely used as a host for secretion of heterologous proteins in biotech applications, but all the commonly used expression systems are derived from a single genetic background. Here, genetic mapping in K. phaffii identifies gene variants that affect the yield of secreted foreign proteins. [ABSTRACT FROM AUTHOR]

The opportunistic pathogen Pseudomonas aeruginosa is one of leading causes of disability and mortality worldwide and the world health organisation has listed it with the highest priority for the need of new antimicrobial therapies. P. aeruginosa strains responsible for the poorest clinical outcomes express either ExoS or ExoU, which are injected into target host cells via the type III secretion system (T3SS). ExoS is a bifunctional cytotoxin that promotes intracellular survival of invasive P. aeruginosa by preventing targeting of the bacteria to acidified intracellular compartments. ExoU is a phospholipase which causes destruction of host cell plasma membranes, leading to acute tissue damage and bacterial dissemination. Fluoroquinolones are usually employed as a first line of therapy as they have been shown to be more active against P. aeruginosa in vitrothan other antimicrobial classes. Their overuse over the past decade, however, has resulted in the emergence of antibiotic resistance. In certain clinical situations, aminoglycosides have been shown to be more effective then fluoroquinolones, despite their reduced potency towards P. aeruginosa in vitro. In this study, we evaluated the effects of fluoroquinolones (moxifloxacin and ciprofloxacin) and aminoglycosides (tobramycin and gentamycin) on T3SS expression and toxicity, in corneal epithelial cell infection models. We discovered that tobramycin disrupted T3SS expression and reduced both ExoS and ExoU mediated cytotoxicity, protecting infected HCE-t cells at concentrations below the minimal inhibitory concentration (MIC). The fluoroquinolones moxifloxacin and ciprofloxacin, however, upregulated the T3SS and did not inhibit and may have increased the cytotoxic effects of ExoS and ExoU. [ABSTRACT FROM AUTHOR]

The primary aim of this study was to identify the physical fitness profile of Irish adolescents playing hurling, camogie, and Gaelic football according to age and gender. To establish relationships between the physical fitness tests and anthropometry for these male and female adolescents. This cross-sectional study design included 311 adolescents between age of 13-18 years. Subjects completed a physical fitness test battery of 9 tests which included the following: height, body mass, modified sit and reach (SR), seated medicine ball throw (MBT), countermovement jump (CMJ), standing long jump (SLJ), 15-m sprint, 505 agility, and a 6-minute modified Cooper test (m-CT). Female subjects scored significantly higher in the SR than males, and older adolescents scored significantly higher than younger adolescents (p < 0.05). In the remaining fitness tests (MBT, SLJ, CMJ, 15-m sprint, agility, and m-CT), males outperformed females, males had greater anthropometry scores than females, and older adolescents outperformed and had higher changes in anthropometry than younger counterparts (p < 0.05). Normative data for gender and age-specific percentile values (5th, 10th, 25th, 50th, 75th, 90th, and 95th) for these tests in these adolescent players are provided. These data are useful for clubs, parents, coaches, clinicians, and secondary schools in monitoring adolescents and to provide training programs that develop athletic performance. [ABSTRACT FROM AUTHOR]

Saccharomyces genomes are highly collinear and show relatively little structural variation, both within and between species of this yeast genus. We investigated the only common inversion polymorphism known in S. cerevisiae, which affects a 24-kb 'flip/flop' region containing 15 genes near the centromere of chromosome XIV. The region exists in two orientations, called reference (REF) and inverted (INV). Meiotic recombination in this region is suppressed in crosses between REF and INV orientation strains such as the BY x RM cross. We find that the inversion polymorphism is at least 17 million years old because it is conserved across the genus Saccharomyces. However, the REF and INV isomers are not ancient alleles but are continually being re-created by re-inversion of the region within each species. Inversion occurs due to continual homogenization of two almost identical 4-kb sequences that form an inverted repeat (IR) at the ends of the flip/flop region. The IR consists of two pairs of genes that are specifically and strongly expressed during the late stages of sporulation. We show that one of these gene pairs, YNL018C/YNL034W, codes for a protein that is essential for spore formation. YNL018C and YNL034W are the founder members of a gene family, Centroid, whose members in other Saccharomycetaceae species evolve fast, duplicate frequently, and are preferentially located close to centromeres. We tested the hypothesis that Centroid genes are a meiotic drive system, but found no support for this idea. Author summary: We show that a region of the genome of Saccharomyces yeast species has toggled repeatedly between two alternative orientations for millions of years. The orientation of this 24-kb 'flip/flop' region, near the centromere of chromosome XIV, is polymorphic in S. cerevisiae, S. paradoxus, and probably all other species of the genus Saccharomyces. Both orientations occur in laboratory and wild strains of S. cerevisiae, and meiotic recombination in the flip/flop region is suppressed in crosses between strains having opposite orientations such as S288C and SK1. The changes of orientation are caused by recombination between two sequences that form an inverted repeat flanking the flip/flop region. The inverted repeat contains two genes with roles in sporulation, but it is unclear what evolutionary pressure maintains the inverted repeat structure and causes the genes to undergo continual homogenization. [ABSTRACT FROM AUTHOR]

Governments often make public announcements that call into question firms' misuse of market power. Yet little is known about how firms respond to them. We study gasoline retailers' price responses to antitrust announcements shaming them for price gouging during the COVID‐19 pandemic. We identify price effects using a high‐frequency event‐study leveraging unique real‐time station‐level price data and well‐identified, discrete antitrust announcements. We find evidence of announcement effects that depend on firms' preannouncement margins and hence exposure to being publicly shamed. Public statements by antitrust questioning firms' misuse of market power can indeed contain signals that affect equilibrium outcomes. [ABSTRACT FROM AUTHOR]

We use a field experiment to study price discrimination in a market with price posting and negotiation. Motivated by concerns that low-income consumers do poorly in markets with privately negotiated prices, we built a call center staffed with actors armed with bargaining scripts to reveal negotiated prices and their determinants. Our actors implement sequential bargaining games under incomplete information in the field. By experimentally manipulating how information is revealed, we generate sequences of price offers that allow us to identify price discrimination in negotiations based on retailer perceptions of consumers' search and switching costs. We also document differences in price distributions between entrants and incumbents, reflecting differences in captivity of their respective consumer bases. Finally, we show that higher prices paid by lower-income subsidy recipients in our market is not due to discriminatory targeting; they can be explained by variation in consumer willingness and ability to search and bargain. [ABSTRACT FROM AUTHOR]

Summary: A 3‐year‐old Thoroughbred filly presented with a several‐month history of weight loss, polydipsia and polyuria, intermittent diarrhoea and behavioural changes and intermittently uncoordinated gait. Neurological examination revealed hyperexcitability, bilaterally reduced pupillary light reflexes and quadrilateral ataxia with proprioceptive deficits more obvious in the forelimbs than in the hindlimbs. A multifocal neurological lesion was suspected. The laboratory finding of a persistent hyperchloraemia and an apparent negative anion gap prompted measurement of serum bromide concentration and subsequently confirmed bromide intoxication. Further questioning of the trainer revealed that the filly had been administered oral potassium bromide for behavioural modification over several months. Clinical signs of bromide intoxication resolved within 20 days following the last bromide administration, without specific medical intervention. This case report describes the risk of inadvertent bromide overdosing in horses and highlights the need for control of bromide use in the equine industry. [ABSTRACT FROM AUTHOR]

The bio-derived platform molecule levoglucosenone (LGO, 1), which is the precursor to the green solvent Cyrene® (2), has been converted, at multi-gram scale, into its pseudo-enantiomer (iso -LGO, 2) and then reduced to iso -Cyrene (4). A less effective synthesis of this last compound from D -glucose is also described. Various physicochemical as well as certain toxicological properties of compound 4 are reported and compared to those established for the now commercially available Cyrene® (2). Such studies reveal that there are significant enough differences in the properties of the sustainably-derived Cyrene® (2) and isomer 4 (iso -Cyrene) to suggest they will exert complementary effects as solvents in a range of settings. Cyrene® (2), a commercially available solvent, is obtained by hydrogenation of levoglucosenone (LGO, 1), itself the product of pyrolysis of acid-treated cellulose. iso -Cyrene (4) has now been prepared from iso -LGO (3) and shown to display certain complementary solvent properties. [ABSTRACT FROM AUTHOR]

Two sets of carbohydrate‐NHC hybrid iridium complexes were synthesised in order to combine properties of carbohydrates and triazolylidene (trz) ligands in organometallic catalysis. One set features a direct trz linkage to the anomeric carbohydrate carbon, while the second set is comprised of an ethyl linker between the two functional units. Deprotection of the carbohydrate afforded hybrid complexes that efficiently catalyse the direct hydrogenation of ketones in water. The catalytic activity of the hybrid complexes was influenced by the pH of the aqueous medium and surpassed the activity of carbohydrate‐free or acetyl‐protected analogues (>90 % vs 13 % yield). While no enantiomeric induction was observed for the ethyl‐linked hybrids, a moderate enantiomeric excess (ee) was induced by the directly linked systems. Moreover, these carbohydrate‐trz hybrid complexes displayed mixed inhibitory activity towards a glycosidase from H. orenii that contain a glucose binding site. [ABSTRACT FROM AUTHOR]

In autism research, the impact of the hidden curriculum within higher education remains neglected. The published experiences of undergraduate and postgraduate students with Autism Spectrum Disorder indicate that social issues present a universal problem for this demographic. By being less able to take advantage of the social aspects of their courses, such as interactions with peers and supervisors, autistic students could be left at a disadvantage in their current studies and beyond. Opening formal research questions into the impact of the hidden curriculum on the learning experience of autistic students in higher education are required to highlight this issue. Investigating the most effective forms of hidden curriculum access could provide better insight into how support can be personalised to the needs of these students. [ABSTRACT FROM AUTHOR]

Lager brewing first occurred in Bavaria in the 15th century, associated with restrictions of brewing to colder months. The lager yeast, Saccharomyces pastorianus , is cold tolerant. It is a hybrid between Saccharomyces cerevisiae and Saccharomyces eubayanus , and has been found only in industrial settings. Natural isolates of S. eubayanus were first discovered in Patagonia 11 years ago. They have since been isolated from China, Tibet, New Zealand, and North America, but not from Europe. Here, we describe the first European strains UCD646 and UCD650, isolated from a wooded area on a university campus in Dublin, Ireland. We generated complete chromosome level assemblies of both genomes using long- and short-read sequencing. The UCD isolates belong to the Holarctic clade. Genome analysis shows that isolates similar to the Irish strains contributed to the S. eubayanus component of S. pastorianus , but isolates from Tibet made a larger contribution. [ABSTRACT FROM AUTHOR]