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Coal seams with high CO2 gas contents can be difficult to drain gas for outburst management. Coal has a high affinity for CO2 with adsorption capacities typically twice that of CH4. This paper presents an analysis of nitrogen injection into coal to enhance drainage of high CO2 gas contents. Core flooding experiments were conducted where nitrogen was injected into coal core samples from two Australian coal mining basins with initial CO2 gas contents and pressures that could be encountered during underground mining. Nitrogen effectively displaced the CO2 with mass balance analysis finding there was only approximately 6%–7% of the original CO2 gas content residual at the end of the core flood. Using a modified version of the SIMED II reservoir simulator, the core flooding experiments were history matched to determine the nitrogen and methane sorption times. It was found that a triple porosity model (a simple extension of the Warren and Root dual porosity model) was required to accurately describe the core flood observations. The estimated model properties were then used in reservoir simulation studies comparing enhanced drainage with conventional drainage with underground in seam boreholes. For the cases considered, underground in seam boreholes were found to provide shorter drainage lead times than enhanced drainage to meet a safe gas content for outburst management. Keywords: Gas drainage, High CO2, ECBM, Reservoir simulation

Abstract Dendritic release of dopamine activates dopamine D2 autoreceptors, which are inhibitory G protein-coupled receptors (GPCRs), to decrease the excitability of dopamine neurons. This study used tagged D2 receptors to identify the localization and distribution of these receptors in living midbrain dopamine neurons. GFP-tagged D2 receptors were found to be unevenly clustered on the soma and dendrites of dopamine neurons within the substantia nigra pars compacta (SNc). Physiological signaling and desensitization of the tagged receptors were not different from wild type receptors. Unexpectedly, upon desensitization the tagged D2 receptors were not internalized. When tagged D2 receptors were expressed in locus coeruleus neurons, a desensitizing protocol induced significant internalization. Likewise, when tagged µ-opioid receptors were expressed in dopamine neurons they too were internalized. The distribution and lack of agonist-induced internalization of D2 receptors on dopamine neurons indicate a purposefully regulated localization of these receptors.

Abstract Adherence to norms and interventions to norm violations are two important forms of social behaviour modelled in economic games. While both appear to serve a prosocial function, they may represent separate mechanisms corresponding with distinct emotional and psychological antecedents, and thus may be predicted by different personality traits. In this study, we compared adherence to fairness norms in the dictator game with responses to violations of the same norms in third-party punishment and recompensation games with respect to prosocial traits from the Big Five and HEXACO models of personality. The results revealed a pattern of differential relations between prosocial traits and game behaviours. While norm adherence in the dictator game was driven by traits reflecting good manners and non-aggression (the politeness aspect of Big Five agreeableness and HEXACO honesty-humility), third-party recompensation of victims—and to a lesser extent, punishment of offenders—was uniquely driven by traits reflecting emotional concern for others (the compassion aspect of Big Five agreeableness). These findings demonstrate the discriminant validity between similar prosocial constructs and highlight the different prosocial motivations underlying economic game behaviours.

Abstract Background A key step in the design of a randomised controlled trial (RCT) is the estimation of the number of participants needed. By far the most common approach is to specify a target difference and then estimate the corresponding sample size; this sample size is chosen to provide reassurance that the trial will have high statistical power to detect such a difference between the randomised groups (at the planned statistical significance level). The sample size has many implications for the conduct of the study, as well as carrying scientific and ethical aspects to its choice. Despite the critical role of the target difference for the primary outcome in the design of an RCT, the manner in which it is determined has received little attention. This article reports the protocol of the Difference ELicitation in TriAls (DELTA2) project, which will produce guidance on the specification and reporting of the target difference for the primary outcome in a sample size calculation for RCTs. Methods/design The DELTA2 project has five components: systematic literature reviews of recent methodological developments (stage 1) and existing funder guidance (stage 2); a Delphi study (stage 3); a 2-day consensus meeting bringing together researchers, funders and patient representatives, as well as one-off engagement sessions at relevant stakeholder meetings (stage 4); and the preparation and dissemination of a guidance document (stage 5). Discussion Specification of the target difference for the primary outcome is a key component of the design of an RCT. There is a need for better guidance for researchers and funders regarding specification and reporting of this aspect of trial design. The aim of this project is to produce consensus based guidance for researchers and funders.

Background: The randomised controlled trial is widely considered to be the gold standard study for comparing the effectiveness of health interventions. Central to its design is a calculation of the number of participants needed (the sample size) for the trial. The sample size is typically calculated by specifying the magnitude of the difference in the primary outcome between the intervention effects for the population of interest. This difference is called the ‘target difference’ and should be appropriate for the principal estimand of interest and determined by the primary aim of the study. The target difference between treatments should be considered realistic and/or important by one or more key stakeholder groups. Objective: The objective of the report is to provide practical help on the choice of target difference used in the sample size calculation for a randomised controlled trial for researchers and funder representatives. Methods: The Difference ELicitation in TriAls2 (DELTA2) recommendations and advice were developed through a five-stage process, which included two literature reviews of existing funder guidance and recent methodological literature; a Delphi process to engage with a wider group of stakeholders; a 2-day workshop; and finalising the core document. Results: Advice is provided for definitive trials (Phase III/IV studies). Methods for choosing the target difference are reviewed. To aid those new to the topic, and to encourage better practice, 10 recommendations are made regarding choosing the target difference and undertaking a sample size calculation. Recommended reporting items for trial proposal, protocols and results papers under the conventional approach are also provided. Case studies reflecting different trial designs and covering different conditions are provided. Alternative trial designs and methods for choosing the sample size are also briefly considered. Conclusions: Choosing an appropriate sample size is crucial if a study is to inform clinical practice. The number of patients recruited into the trial needs to be sufficient to answer the objectives; however, the number should not be higher than necessary to avoid unnecessary burden on patients and wasting precious resources. The choice of the target difference is a key part of this process under the conventional approach to sample size calculations. This document provides advice and recommendations to improve practice and reporting regarding this aspect of trial design. Future work could extend the work to address other less common approaches to the sample size calculations, particularly in terms of appropriate reporting items. Funding: Funded by the Medical Research Council (MRC) UK and the National Institute for Health Research as part of the MRC–National Institute for Health Research Methodology Research programme.

Changes in cell proliferation define transitions from tissue growth to physiological homeostasis. In tendons, a highly organized extracellular matrix undergoes significant postnatal expansion to drive growth, but once formed, it appears to undergo little turnover. However, tendon cell activity during growth and homeostatic maintenance is less well defined. Using complementary methods of genetic H2B-GFP pulse-chase labeling and BrdU incorporation in mice, we show significant postnatal tendon cell proliferation, correlating with longitudinal Achilles tendon growth. Around day 21, there is a transition in cell turnover with a significant decline in proliferation. After this time, we find low amounts of homeostatic tendon cell proliferation from 3 to 20 months. These results demonstrate that tendons harbor significant postnatal mitotic activity, and limited, but detectable activity in adult and aged stages. It also points towards the possibility that the adult tendon harbors resident tendon progenitor populations, which would have important therapeutic implications.

Abstract Invertebrates are commonly ignored in conservation planning due to their vast diversity, difficulties with species identification, a poor understanding of their spatial patterns, and the impracticability of carrying out comprehensive sampling. Conservation planning for fauna is therefore often based on patterns of diversity and distribution of vertebrates, under the assumption that these are representative of animal diversity more generally. Here, we evaluate how well vertebrates act as umbrellas for invertebrate diversity and distribution in a highly diverse tropical savanna landscape, and we investigate the effect of vertebrate sampling intensity (i.e., number of surveys) on congruence results. We assessed congruence between each of the four classes of terrestrial vertebrates (amphibians, reptiles, birds, and mammals) and twelve invertebrate families (representing four dominant invertebrate taxa: ants, beetles, flies, and spiders) by applying a range of modeling approaches to analyze patterns of cross‐taxon congruence in species richness and composition across sampling sites. To investigate drivers of congruence, we applied generalized and distance‐based linear models to identify environmental associations of richness and composition for each taxon, then examined variation in environmental associations across taxa. Vertebrate and invertebrate richness was weakly (

The soil bacteria diversity and corresponding environmental data made available here are from a 72-field plot experiment testing the effect of pulse frequency in nine wheat-based rotation systems, in the semiarid prairie. The data include sequences of the V6–V8 regions of bacterial 16S rDNA from soil and root extracts, generated using Roche GS FLX Titanium technology, and associated environmental data, specifically levels of soil organic carbon, total carbon, total nitrogen, total phosphorus, pH, electrical conductivity, and extractible sulfate sulfur, copper, iron, manganese, zinc, potassium, nitrate nitrogen, phosphate phosphorus, calcium, and magnesium in the 0–15 cm soil layer, and mineral nitrogen and phosphate in the 0–120 cm soil layer. The grain yield of wheat in the last (4th) phase of the crop rotation systems is also given. The data can be used in meta-analyses of the effect of pea, lentil and chickpea in wheat-based cropping systems on soil bacterial diversity or for monitoring the evolution of soil bacteria communities in cultivated prairie soils in the context of climate change. Samples were collected between 2012 and 2014.

We compared the performance of two commonly used genotyping platforms, genotyping-by-sequencing (GBS) and single nucleotide polymorphism-arrays (SNP), to investigate the extent and pattern of genetic variation within a collection of 1,000 diverse barley genotypes selected from the German Federal ex situ GenBank hosted at IPK Gatersleben. Each platform revealed equivalent numbers of robust bi-allelic SNPs (39,733 and 37,930 SNPs for the 50K SNP-array and GBS datasets respectively). A small overlap of 464 SNPs was common to both platforms, indicating that the methodologies we used selectively access informative polymorphism in different portions of the barley genome. Approximately half of the GBS dataset was comprised of SNPs with minor allele frequencies (MAFs) below 1%, illustrating the power of GBS to detect rare alleles in diverse germplasm collections. While desired for certain applications, the highly robust calling of alleles at the same SNPs across multiple populations is an advantage of the SNP-array, allowing direct comparisons of data from related or unrelated studies. Overall MAFs and diversity statistics (π) were higher for the SNP-array data, potentially reflecting the conscious removal of markers with a low MAF in the ascertainment population. A comparison of similarity matrices revealed a positive correlation between both approaches, supporting the validity of using either for entire GenBank characterization. To explore the potential of each dataset for focused genetic analyses we explored the outcomes of their use in genome-wide association scans for row type, growth habit and non-adhering hull, and discriminant analysis of principal components for the drivers of sub-population differentiation. Interpretation of the results from both types of analysis yielded broadly similar conclusions indicating that choice of platform used for such analyses should be determined by the research question being asked, group preferences and their capabilities to extract and interpret the different types of output data easily and quickly. Access to the requisite infrastructure for running, processing, analyzing, querying, storing, and displaying either datatype is an additional consideration. Our investigations reveal that for barley the cost per genotyping assay is less for SNP-arrays than GBS, which translates to a cost per informative datapoint being significantly lower for the SNP-array.

Cancer and antimicrobial resistance to antibiotics are two of the most worrying healthcare concerns that humanity is facing nowadays. Some of the most promising solutions for these healthcare problems may come from nanomedicine. While the traditional synthesis of nanomaterials is often accompanied by drawbacks such as high cost or the production of toxic by-products, green nanotechnology has been presented as a suitable solution to overcome such challenges. In this work, an approach for the synthesis of tellurium (Te) nanostructures in aqueous media has been developed using aloe vera (AV) extracts as a unique reducing and capping agent. Te-based nanoparticles (AV-TeNPs), with sizes between 20 and 60 nm, were characterized in terms of physicochemical properties and tested for potential biomedical applications. A significant decay in bacterial growth after 24 h was achieved for both Methicillin-resistant Staphylococcus aureus and multidrug-resistant Escherichia coli at a relative low concentration of 5 µg/mL, while there was no cytotoxicity towards human dermal fibroblasts after 3 days of treatment. AV-TeNPs also showed anticancer properties up to 72 h within a range of concentrations between 5 and 100 µg/mL. Consequently, here, we present a novel and green approach to produce Te-based nanostructures with potential biomedical applications, especially for antibacterial and anticancer applications.

Access to clean and affordable energy is vital for health, well-being, and socio-economic development. This critical service remains unrealised in many African countries. Women’s empowerment is known to promote healthcare service use, child nutrition and agricultural productivity. In Africa, however, little is known about the relationship between women’s empowerment and household fuel use, and if it varies between countries. Therefore, we assessed the cross-sectional associations between women’s empowerment and cooking fuel use in 31 African countries. We analysed individual-level data from the Demographic and Health Surveys, conducted between 2003 and 2018 ( n = 264 269 [women-household pairs]). We used a novel, Africa-specific index (survey-based women’s empowerment index), including three domains of empowerment: decision-making, attitude to violence, and social independence. Hierarchical logistic regression models assessed the associations between women’s empowerment domains and the type of fuel used in the household (‘clean’: electricity, liquefied petroleum gas (LPG), biogas or natural gas; ‘polluting’: solid fuels or kerosene). Results were adjusted for household- and area-level covariates, and expressed as odds ratios (OR). The 31 country-specific estimates were combined using meta-analysis. Approximately 43 778 (14.5%) of households used clean fuels. Overall, between 12/31 and 22/31 country-level estimates showed a significant association between a one standard deviation increase in empowerment domains (higher scores indicate greater empowerment), and higher odds of using clean fuel as primary energy source for cooking. The random-effect meta-analytic estimates showed that increased empowerment was associated with higher odds of using clean fuel for attitude to violence (OR = 1.22; 95% CI: 1.12–1.33), social independence (OR = 1.34; 95% CI: 1.28–1.42), and decision-making (OR = 1.10; 95% CI: 1.05–1.15). These findings suggest that empowering women, in addition to being crucial in its own right, has potential to accelerate transitions to clean fuel in Africa, although these associations vary between countries.

The adverse effects of air pollution during pregnancy have been studied intensively, but mainly utilizing linear and logistic models, which generally yield little information about how air pollution may change the distribution of birth weight in populations. We aimed to examine the effects of fine particulate matter (PM _2.5 ) on quantiles of birth weight, and if effects were heterogeneous in different populations and regions. We used a prospective cohort study of 196 283 singleton term live births from 16 counties across China during 2014–2018. PM _2.5 exposure for full gestation, each trimester and last gestational month were assessed by Inverse Distance Weighting interpolation. Linear and quantile regression were conducted to estimate associations between PM _2.5 exposure and mean birth weight, as well as birth weight distribution, with birthweight z -score as the main outcome. Stratified analyses and Cochran Q tests were conducted by maternal and geographical characteristics. Each 10 µ g m ^−3 increase in average PM _2.5 over the entire pregnancy was associated with reduced birthweight z -score (−0.010, 95% CI: −0.015, −0.005) and birth weight (−3.21 g, 95% CI: −5.27, −1.15). In quantile regression, more pronounced effects were observed in lower and intermediate quantiles, with a decrease of 0.021 (95% CI: 0.033, 0.009) and 0.009 (95% CI: 0.015, 0.002) in the 5th and 50th quantiles of birthweight z -score, respectively. Additionally, we observed stronger associations among well-educated, migrant and primiparous mothers as well as in coastal areas. Maternal exposure to PM _2.5 was associated with reduction in birth weight, especially for those with very low birth weight. Well-educated, migrant and primiparous mothers, as well as births in coastal areas may be more sensitive to PM _2.5 in our study population. The results may be relevant to targeted public health interventions to reduce maternal exposure to air pollution.

Soil respiration (i.e. from soils and roots) provides one of the largest global fluxes of carbon dioxide (CO _2 ) to the atmosphere and is likely to increase with warming, yet the magnitude of soil respiration from rapidly thawing Arctic-boreal regions is not well understood. To address this knowledge gap, we first compiled a new CO _2 flux database for permafrost-affected tundra and boreal ecosystems in Alaska and Northwest Canada. We then used the CO _2 database, multi-sensor satellite imagery, and random forest models to assess the regional magnitude of soil respiration. The flux database includes a new Soil Respiration Station network of chamber-based fluxes, and fluxes from eddy covariance towers. Our site-level data, spanning September 2016 to August 2017, revealed that the largest soil respiration emissions occurred during the summer (June–August) and that summer fluxes were higher in boreal sites (1.87 ± 0.67 g CO _2 –C m ^−2 d ^−1 ) relative to tundra (0.94 ± 0.4 g CO _2 –C m ^−2 d ^−1 ). We also observed considerable emissions (boreal: 0.24 ± 0.2 g CO _2 –C m ^−2 d ^−1 ; tundra: 0.18 ± 0.16 g CO _2 –C m ^−2 d ^−1 ) from soils during the winter (November–March) despite frozen surface conditions. Our model estimates indicated an annual region-wide loss from soil respiration of 591 ± 120 Tg CO _2 –C during the 2016–2017 period. Summer months contributed to 58% of the regional soil respiration, winter months contributed to 15%, and the shoulder months contributed to 27%. In total, soil respiration offset 54% of annual gross primary productivity (GPP) across the study domain. We also found that in tundra environments, transitional tundra/boreal ecotones, and in landscapes recently affected by fire, soil respiration often exceeded GPP, resulting in a net annual source of CO _2 to the atmosphere. As this region continues to warm, soil respiration may increasingly offset GPP, further amplifying global climate change.

The toxicity of ultrafine particles (UFPs) on blood pressure (BP) has not been well studied. We aimed to evaluate the associations of long-term UFP exposure with different components of BP and the risk of prehypertension/hypertension. We included a total of 24 845 Chinese adults (18–74 years old) in a cross-sectional survey (Liaoning province, China). The 4 year (2006–2009) average concentrations of UFP was estimated using a chemical transport model. We measured systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP), prehypertension and hypertension. We used a generalized linear mixed model to examine the associations while controlling for important individual covariates. One unit (1 μ g m ^−3 ) increase in UFP was associated with an increase in SBP of 1.52 mm Hg [95% confidence interval (CI): 0.48–2.55], DBP of 0.55 mm Hg (95% CI: 0.01–1.08) in DBP, MAP of 0.92 mm Hg (95% CI: 0.23–1.61) and PP of 0.62 mm Hg (95% CI: 0.05–1.20). The UFP-BP associations were stronger in women than in men. One unit increase in UFP was associated with an increased risk of hypertension and prehypertension (OR = 1.23, 95% CI: 1.09–1.38; OR = 1.12, 95% CI: 1.04–1.21) compared to normotension group, and these associations were stronger in overweight/obese participants. Our study showed that long-term exposure to UFP was associated with elevated BP and higher odds of hypertension. These findings suggest that strategies to monitor and reduce UFPs, which are not a regulated pollutant, could have beneficial cardiovascular effects.

An estimated 1700 Pg of carbon is frozen in the Arctic permafrost and the fate of this carbon is unclear because of the complex interaction of biophysical, ecological and biogeochemical processes that govern the Arctic carbon budget. Two key processes determining the region’s long-term carbon budget are: (a) carbon uptake through increased plant growth, and (b) carbon release through increased heterotrophic respiration (HR) due to warmer soils. Previous predictions for how these two opposing carbon fluxes may change in the future have varied greatly, indicating that improved understanding of these processes and their feedbacks is critical for advancing our predictive ability for the fate of Arctic peatlands. In this study, we implement and analyze a vertically-resolved model of peatland soil carbon into a cohort-based terrestrial biosphere model to improve our understanding of how on-going changes in climate are altering the Arctic carbon budget. A key feature of the formulation is that accumulation of peat within the soil column modifies its texture, hydraulic conductivity, and thermal conductivity, which, in turn influences resulting rates of HR within the soil column. Analysis of the model at three eddy covariance tower sites in the Alaskan tundra shows that the vertically-resolved soil column formulation accurately captures the zero-curtain phenomenon, in which the temperature of soil layers remain at or near 0 °C during fall freezeback due to the release of latent heat, is critical to capturing observed patterns of wintertime respiration. We find that significant declines in net ecosystem productivity (NEP) occur starting in 2013 and that these declines are driven by increased HR arising from increased precipitation and warming. Sensitivity analyses indicate that the cumulative NEP over the decade responds strongly to the estimated soil carbon stock and more weakly to vegetation abundance at the beginning of the simulation.

Cells are continually exposed to stressful events, which are overcome by the activation of a number of genetic pathways. The integrated stress response (ISR) is a large component of the overall cellular response to stress, which ultimately functions through the phosphorylation of the alpha subunit of eukaryotic initiation factor-2 (eIF2α) to inhibit the energy-taxing process of translation. This response is instrumental in the inhibition of viral infection and contributes to evolution in viruses. Mammalian orthoreovirus (MRV), an oncolytic virus that has shown promise in over 30 phase I–III clinical trials, has been shown to induce multiple arms within the ISR pathway, but it successfully evades, modulates, or subverts each cellular attempt to inhibit viral translation. MRV has not yet received Food and Drug Administration (FDA) approval for general use in the clinic; therefore, researchers continue to study virus interactions with host cells to identify circumstances where MRV effectiveness in tumor killing can be improved. In this review, we will discuss the ISR, MRV modulation of the ISR, and discuss ways in which MRV interaction with the ISR may increase the effectiveness of cancer therapeutics whose modes of action are altered by the ISR.

Existen diferentes opciones para la corrección quirúrgica del pie plano, y la aplicación de una u otra técnica en un paciente concreto puede estar muy infl uenciada por la experiencia previa del cirujano, su educación/entrenamiento y/o sus preferencias personales. Un profundo entendimiento de la infl uencia biomecánica relacionada con el pie plano y de las diferencias conceptuales en los distintos abordajes para la corrección de las fuerzas patológicas es fundamental. Existen muchas combinaciones de técnicas que pueden ofrecer resultados satisfactorios y es recomendable para todos los cirujanos estar familiarizados con todos estos procedimientos para adecuar la selección de los mismos en cada paciente concreto. El presente artículo aúna la bibliografía reciente más relevante sobre la corrección del pie plano junto con la experiencia personal del autor para el tratamiento quirúrgico esta deformidad por más de 25 años.

Surface meltwater generated on ice shelves fringing the Antarctic Ice Sheet can drive ice-shelf collapse, leading to ice sheet mass loss and contributing to global sea level rise. A quantitative assessment of supraglacial lake evolution is required to understand the influence of Antarctic surface meltwater on ice-sheet and ice-shelf stability. Cloud computing platforms have made the required remote sensing analysis computationally trivial, yet a careful evaluation of image processing techniques for pan-Antarctic lake mapping has yet to be performed. This work paves the way for automating lake identification at a continental scale throughout the satellite observational record via a thorough methodological analysis. We deploy a suite of different trained supervised classifiers to map and quantify supraglacial lake areas from multispectral Landsat-8 scenes, using training data generated via manual interpretation of the results from k-means clustering. Best results are obtained using training datasets that comprise spectrally diverse unsupervised clusters from multiple regions and that include rock and cloud shadow classes. We successfully apply our trained supervised classifiers across two ice shelves with different supraglacial lake characteristics above a threshold sun elevation of 20°, achieving classification accuracies of over 90% when compared to manually generated validation datasets. The application of our trained classifiers produces a seasonal pattern of lake evolution. Cloud shadowed areas hinder large-scale application of our classifiers, as in previous work. Our results show that caution is required before deploying ‘off the shelf’ algorithms for lake mapping in Antarctica, and suggest that careful scrutiny of training data and desired output classes is essential for accurate results. Our supervised classification technique provides an alternative and independent method of lake identification to inform the development of a continent-wide supraglacial lake mapping product.

Melt and supraglacial lakes are precursors to ice shelf collapse and subsequent accelerated ice sheet mass loss. We used data from the Landsat 8 and Sentinel-2 satellites to develop a threshold-based method for detection of lakes found on the Antarctic ice shelves, calculate their depths and thus their volumes. To achieve this, we focus on four key areas: the Amery, Roi Baudouin, Nivlisen, and Riiser-Larsen ice shelves, which are all characterized by extensive surface meltwater features. To validate our products, we compare our results against those obtained by an independent method based on a supervised classification scheme (e.g., Random Forest algorithm). Additional verification is provided by manual inspection of results for nearly 1000 Landsat 8 and Sentinel-2 images. Our dual-sensor approach will enable constructing high-resolution time series of lake volumes. Therefore, to ensure interoperability between the two datasets, we evaluate depths from contemporaneous Landsat 8 and Sentinel-2 image pairs. Our assessments point to a high degree of correspondence, producing an average R2 value of 0.85, no bias, and an average RMSE of 0.2 m. We demonstrate our method’s ability to characterize lake evolution by presenting first evidence of drainage events outside of the Antarctic Peninsula on the Amery Ice shelf. The methods presented here pave the way to upscaling throughout the Landsat 8 and Sentinel-2 observational record across Antarctica to produce a first-ever continental dataset of supraglacial lake volumes. Such a dataset will improve our understanding of the influence of surface hydrology on ice shelf stability, and thus, future projections of Antarctica’s contribution to sea level rise.

Theories in personality neuroscience must aim to be consistent with several levels of explanation. If we view personality traits as constructs located only at the psychological level, we must still make their explanations compatible with observations and theories at lower levels, particularly with what we know at the neural level. If we view personality traits as constructs located only at the neural level, we will still need to predict their emergent effects at the psychological level. Personality theory at present treats traits as psychological-level constructs, with even the recent neurally oriented Cybernetic Big Five Theory specified in terms of a “conceptual nervous system” and not requiring complete or immediate translation into neural mechanisms. Here, we argue for the existence of phylogenetically old, neural-level traits that are substantially conserved across many vertebrate species. We first ask what known mechanisms control trait-like properties of neural systems: Focusing on hormones, the GABAA receptor, and amine neurotransmitter systems. We derive from what we know about these sources of neuronal modulation some metatheoretical principles to guide the future development of those aspects of personality theory, starting with neural-level trait constructs and drawing implications for higher-level trait psychology observations. Current descriptive approaches such as the Big Five are an essential precursor to personality neuroscience, but may not map one-to-one to the mechanisms and constructs of a neuroscience-based approach to traits.

ABSTRACT Staphylococcus aureus is a human pathogen that has developed several approaches to evade the immune system, including a strategy to resist oxidative killing by phagocytes. This resistance is mediated by production of superoxide dismutase (SOD) enzymes which use manganese as a cofactor. S. aureus encodes two manganese ion transporters, MntABC and MntH, and a possible Nramp family manganese transporter, exemplified by S. aureus N315 SA1432. Their relative contributions to manganese transport have not been well defined in clinically relevant isolates. For this purpose, insertional inactivation mutations were introduced into mntC, mntH, and SA1432 individually and in combination. mntC was necessary for full resistance to methyl viologen, a compound that generates intracellular free radicals. In contrast, strains with an intact mntH gene had a minimal increase in resistance that was revealed only in mntC strains, and no change was observed upon mutation of SA1432 in strains lacking both mntC and mntH. Similarly, MntC alone was required for high cellular SOD activity. In addition, mntC strains were attenuated in a murine sepsis model. To further link these observations to manganese transport, an S. aureus MntC protein lacking manganese binding activity was designed, expressed, and purified. While circular dichroism experiments demonstrated that the secondary and tertiary structures of this protein were unaltered, a defect in manganese binding was confirmed by isothermal titration calorimetry. Unlike complementation with wild-type mntC, introduction of the manganese-binding defective allele into the chromosome of an mntC strain did not restore resistance to oxidative stress or virulence. Collectively, these results underscore the importance of MntC-dependent manganese transport in S. aureus oxidative stress resistance and virulence. IMPORTANCE Work outlined in this report demonstrated that MntC-dependent manganese transport is required for S. aureus virulence. These study results support the model that MntC-specific antibodies elicited by a vaccine have the potential to disrupt S. aureus manganese transport and thus abrogate to its virulence.

The association of plants and microbial communities is crucial for crop production, and host plants influence the composition of rhizosphere microbiomes. Pulse crops play an important role in the development of sustainable cropping systems, and producers in the Canadian prairies often increase the frequency of pulses in their cropping systems. In this study, we determined the shifts in the fungal community of pea (Pisum sativum L.) rhizosphere, as influenced by the frequency of pulses in rotation, using high throughput sequencing. Six cropping systems containing pea (P), lentil (Lens culinaris Medik., L), hybrid canola (Brassica napus L., C), wheat (Triticum aestivum L., W), and oat (Avena sativa L., O) in different intensities were tested. The fungal communities were assessed at the flowering stage in the fourth and fifth year of the 4-year rotations. Cropping system had a significant impact on the composition of the rhizosphere fungal community, and the effect of crop rotation sequence was greater and explained more of the variation than the effect of previous crops. The rotation with consecutive pulses (WPLP) decreased fungal evenness and increased the proportion of pathotrophs. Fusarium was a dominant and ubiquitous pathotrophic genus. Olpidium virulentus, Botrytis cinerea, Fusarium solani, F. graminearum, and Alternaria eichhorniae were generally more abundant in pulse intensive rotations (WPLP, WLOP, and WPOP), the exception being F. solani which was not promoted by lentil. Reads of O. virulentus and B. cinerea were most abundant in pea preceded by lentil followed by the reads of Mortierella elongata in pea preceded by wheat. Pea consistently had higher grain yield when grown in diversified rotations including wheat, canola/lentil, and oat than rotations with two repeated crops (canola or pea). Cropping system affected the soil physicochemical properties, and soil pH was the main driver of fungal community shift. No evidence of beneficial microorganisms involvement in plant productivity was observed, but the high abundance of pathotrophs in pulse intensified rotations suggests the possibility of pathogen buildup in the soil with increasing pulse frequency. Diversifying rotation sequences minimized disease risk and increased pea production, in this study. Careful selection of plant species appears as a strategy for the management of rhizosphere fungal communities and the maintenance of crop production system’s health.

Agriculturally-driven land transformation is increasing globally. Improving phosphorus (P) use efficiency to sustain optimum productivity in diverse ecosystems, based on knowledge of soil P dynamics, is also globally important in light of potential shortages of rock phosphate to manufacture P fertilizer. We investigated P chemical speciation and P cycling with solution 31P nuclear magnetic resonance, P K-edge X-ray absorption near-edge structure spectroscopy, phosphatase activity assays, and shotgun metagenomics in soil samples from long-term agricultural fields containing four different land-use types (native and tame grasslands, annual croplands, and roadside ditches). Across these land use types, native and tame grasslands showed high accumulation of organic P, principally orthophosphate monoesters, and high acid phosphomonoesterase activity but the lowest abundance of P cycling genes. The proportion of inositol hexaphosphates (IHP), especially the neo-IHP stereoisomer that likely originates from microbes rather than plants, was significantly increased in native grasslands than croplands. Annual croplands had the largest variances of soil P composition, and the highest potential capacity for P cycling processes based on the abundance of genes coding for P cycling processes. In contrast, roadside soils had the highest soil Olsen-P concentrations, lowest organic P, and highest tricalcium phosphate concentrations, which were likely facilitated by the neutral pH and high exchangeable Ca of these soils. Redundancy analysis demonstrated that IHP by NMR, potential phosphatase activity, Olsen-P, and pH were important P chemistry predictors of the P cycling bacterial community and functional gene composition. Combining chemical and metagenomics results provides important insights into soil P processes and dynamics in different land-use ecosystems.

The Virginia Libraries journal is making a change to its publication model to publish each article individually with a volume compilation on completion to make the journal’s content as accessible as possible, and to increase the efficiency of our workflow for our authors and readers.

The Virginia Libraries Editorial board presents the first completed volume (Vol. 62) under its new publishing format, in which articles are published individually as they become ready for distribution. A common thread across the volume’s articles is the resourceful use of technology the well established (online professional development delivery) to the cutting edge (proximity beacons for tours).

[This corrects the article DOI: 10.1371/journal.pone.0203304.].

Cancer is a heterogeneous disease, and patient-level genetic assessments can guide therapy choice and impact prognosis. However, little is known about the impact of genetic variability within a tumor, intratumoral heterogeneity (ITH), on disease progression or outcome. Current approaches using bulk tumor specimens can suggest the presence of ITH, but only single-cell genetic methods have the resolution to describe the underlying clonal structures themselves. Current techniques tend to be labor and resource intensive and challenging to characterize with respect to sources of biological and technical variability. We have developed a platform using a microfluidic self-digitization chip to partition cells in stationary volumes for cell imaging and allele-specific PCR. Genotyping data from only confirmed single-cell volumes is obtained and subject to a variety of relevant quality control assessments such as allele dropout, false positive, and false negative rates. We demonstrate single-cell genotyping of the NPM1 type A mutation, an important prognostic indicator in acute myeloid leukemia, on single cells of the cell line OCI-AML3, describing a more complex zygosity distribution than would be predicted via bulk analysis.

Understanding where species occur and how difficult they are to detect during surveys is crucial for designing and evaluating monitoring programs, and has broader applications for conservation planning and management. In this study, we modelled occupancy and the effectiveness of six sampling methods at detecting vertebrates across the Top End of northern Australia. We fitted occupancy-detection models to 136 species (83 birds, 33 reptiles, 20 mammals) of 242 recorded during surveys of 333 sites in eight conservation reserves between 2011 and 2016. For modelled species, mean occupancy was highly variable: birds and reptiles ranged from 0.01-0.81 and 0.01-0.49, respectively, whereas mammal occupancy was lower, ranging from 0.02-0.30. Of the 11 environmental covariates considered as potential predictors of occupancy, topographic ruggedness, elevation, maximum temperature, and fire frequency were retained more readily in the top models. Using these models, we predicted species occupancy across the Top End of northern Australia (293,017 km2) and generated species richness maps for each species group. For mammals and reptiles, high richness was associated with rugged terrain, while bird richness was highest in coastal lowland woodlands. On average, detectability of diurnal birds was higher per day of surveys (0.33 ± 0.09) compared with nocturnal birds per night of spotlighting (0.13 ± 0.06). Detectability of reptiles was similar per day/night of pit trapping (0.30 ± 0.09) as per night of spotlighting (0.29 ± 0.11). On average, mammals were highly detectable using motion-sensor cameras for a week (0.36 ± 0.06), with exception of smaller-bodied species. One night of Elliott trapping (0.20 ± 0.06) and spotlighting (0.19 ± 0.06) was more effective at detecting mammals than cage (0.08 ± 0.03) and pit trapping (0.05 ± 0.04). Our estimates of species occupancy and detectability will help inform decisions about how best to redesign a long-running vertebrate monitoring program in the Top End of northern Australia.

The use of genetically encoded 'self-labeling tags' with chemical fluorophore ligands enables rapid labeling of specific cells in neural tissue. To improve the chemical tagging of neurons, we synthesized and evaluated new fluorophore ligands based on Cy, Janelia Fluor, Alexa Fluor, and ATTO dyes and tested these with recently improved Drosophila melanogaster transgenes. We found that tissue clearing and mounting in DPX substantially improves signal quality when combined with specific non-cyanine fluorophores. We compared and combined this labeling technique with standard immunohistochemistry in the Drosophila brain.

Single-particle tracking (SPT) has become an important method to bridge biochemistry and cell biology since it allows direct observation of protein binding and diffusion dynamics in live cells. However, accurately inferring information from SPT studies is challenging due to biases in both data analysis and experimental design. To address analysis bias, we introduce ‘Spot-On’, an intuitive web-interface. Spot-On implements a kinetic modeling framework that accounts for known biases, including molecules moving out-of-focus, and robustly infers diffusion constants and subpopulations from pooled single-molecule trajectories. To minimize inherent experimental biases, we implement and validate stroboscopic photo-activation SPT (spaSPT), which minimizes motion-blur bias and tracking errors. We validate Spot-On using experimentally realistic simulations and show that Spot-On outperforms other methods. We then apply Spot-On to spaSPT data from live mammalian cells spanning a wide range of nuclear dynamics and demonstrate that Spot-On consistently and robustly infers subpopulation fractions and diffusion constants.

The interferon (IFN)-induced transmembrane (IFITM) proteins are critical mediators of the host antiviral response. Here, we expand the role of IFITM proteins to host defense against intracellular bacterial infection by demonstrating that they restrict Mycobacterium tuberculosis (MTb) intracellular growth. Simultaneous knockdown of IFITM1, IFITM2, and IFITM3 by RNAi significantly enhances MTb growth in human monocytic and alveolar/epithelial cells, whereas individual overexpression of each IFITM impairs MTb growth in these cell types. Furthermore, MTb infection, Toll-like receptor 2 and 4 ligands, and several proinflammatory cytokines induce IFITM1–3 gene expression in human myeloid cells. We find that IFITM3 co-localizes with early and, in particular, late MTb phagosomes, and overexpression of IFITM3 enhances endosomal acidification in MTb-infected monocytic cells. These findings provide evidence that the antiviral IFITMs participate in the restriction of mycobacterial growth, and they implicate IFITM-mediated endosomal maturation in its antimycobacterial activity.

Summary: Interferon γ (IFN-γ) priming sensitizes monocytes and macrophages to lipopolysaccharide (LPS) stimulation, resulting in augmented expression of a set of genes including TNF. Here, we demonstrate that IFN-γ priming of LPS-stimulated TNF transcription requires a distal TNF/LT locus element 8 kb upstream of the TNF transcription start site (hHS-8). IFN-γ stimulation leads to increased DNase I accessibility of hHS-8 and its recruitment of interferon regulatory factor 1 (IRF1), and subsequent LPS stimulation enhances H3K27 acetylation and induces enhancer RNA synthesis at hHS-8. Ablation of IRF1 or targeting the hHS-8 IRF1 binding site in vivo with Cas9 linked to the KRAB repressive domain abolishes IFN-γ priming, but does not affect LPS induction of the gene. Thus, IFN-γ poises a distal enhancer in the TNF/LT locus by chromatin remodeling and IRF1 recruitment, which then drives enhanced TNF gene expression in response to a secondary toll-like receptor (TLR) stimulus. : Interferon γ (IFN-γ) priming is a critical immune event that enhances the monocyte and macrophage response, particularly expression of the TNF gene, to toll-like receptor (TLR) signaling. Chow et al. demonstrate that IFN-γ priming requires a distal enhancer element within the TNF/LT locus, thereby expanding the role of distal regulatory elements in the innate immune response.

Transcription factors bind low-affinity DNA sequences for only short durations. It is not clear how brief, low-affinity interactions can drive efficient transcription. Here, we report that the transcription factor Ultrabithorax (Ubx) utilizes low-affinity binding sites in the Drosophila melanogaster shavenbaby (svb) locus and related enhancers in nuclear microenvironments of high Ubx concentrations. Related enhancers colocalize to the same microenvironments independently of their chromosomal location, suggesting that microenvironments are highly differentiated transcription domains. Manipulating the affinity of svb enhancers revealed an inverse relationship between enhancer affinity and Ubx concentration required for transcriptional activation. The Ubx cofactor, Homothorax (Hth), was co-enriched with Ubx near enhancers that require Hth, even though Ubx and Hth did not co-localize throughout the nucleus. Thus, microenvironments of high local transcription factor and cofactor concentrations could help low-affinity sites overcome their kinetic inefficiency. Mechanisms that generate these microenvironments could be a general feature of eukaryotic transcriptional regulation.

INTRODUCTION:An alarmingly high proportion of the Australian adult population does not meet national physical activity guidelines (57%). This is concerning because physical inactivity is a risk factor for several chronic diseases. In recent years, an increasing emphasis has been placed on the potential for transport and urban planning to contribute to increased physical activity via greater uptake of active transport (walking, cycling and public transport). In this study, we aimed to estimate the potential health gains and savings in health care costs of an Australian city achieving its stated travel targets for the use of active transport. METHODS:Additional active transport time was estimated for the hypothetical scenario of Brisbane (1.1 million population 2013) in Australia achieving specified travel targets. A multi-state life table model was used to estimate the number of health-adjusted life years, life-years, changes in the burden of diseases and injuries, and the health care costs associated with changes in physical activity, fine particle (

Targeted proteolysis of endogenous proteins is desirable as a research toolkit and in therapeutics. CRISPR/Cas9-mediated gene knockouts are irreversible and often not feasible for many genes. Similarly, RNA interference approaches necessitate prolonged treatments, can lead to incomplete knockdowns and are often associated with off-target effects. Targeted proteolysis can overcome these limitations. In this report, we describe an affinity-directed protein missile (AdPROM) system that harbours the von Hippel–Lindau (VHL) protein, the substrate receptor of the Cullin2 (CUL2) E3 ligase complex, tethered to polypeptide binders that selectively bind and recruit endogenous target proteins to the CUL2-E3 ligase complex for ubiquitination and proteasomal degradation. By using synthetic monobodies that selectively bind the protein tyrosine phosphatase SHP2 and a camelid-derived VHH nanobody that selectively binds the human ASC protein, we demonstrate highly efficient AdPROM-mediated degradation of endogenous SHP2 and ASC in human cell lines. We show that AdPROM-mediated loss of SHP2 in cells impacts SHP2 biology. This study demonstrates for the first time that small polypeptide binders that selectively recognize endogenous target proteins can be exploited for AdPROM-mediated destruction of the target proteins.