High-pressure investigations of CaTiO3 up to 60 GPa using X-ray diffraction and Raman spectroscopy

In this work, we investigate calcium titanate (CaTiO3 - CTO) using X-ray diffraction and Raman spectroscopy up to 60 and 55 GPa respectively. Both experiments show that the orthorhombic Pnma structure remains stable up to the highest pressures measured, in contradiction to ab-initio predictions. A fit of the compression data with a second-order Birch-Murnaghan equation of state yields a bulk modulus K0 of 181.0(6) GPa. The orthorhombic distortion is found to increase slightly with pressure, in agreement with previous experiments at lower pressures and the general rules for the evolution of perovskites under pressure. High-pressure polarized Raman spectra also enable us to clarify the Raman mode assignment of CTO and identify the modes corresponding to rigid rotation of the octahedra, A-cation shifts and Ti-O bond stretching. The Raman signature is then discussed in terms of compression mechanisms.Comment: 11 pages, 6 figures, 4 table

An Update on Thiol Signaling: S-Nitrosothiols, Hydrogen Sulfide and a Putative Role for Thionitrous Acid

Long considered vital to antioxidant defenses, thiol chemistry has more recently been recognized to be of fundamental importance to cell signaling. S-nitrosothiols-such as S-nitrosoglutathione (GSNO)-and hydrogen sulfide (H2S) are physiologic signaling thiols that are regulated enzymatically. Current evidence suggests that they modify target protein function primarily through post-translational modifications. GSNO is made by NOS and other metalloproteins; H2S by metabolism of cysteine, homocysteine and cystathionine precursors. GSNO generally acts independently of NO generation and has a variety of gene regulatory, immune modulator, vascular, respiratory and neuronal effects. Some of this physiology is shared with H2S, though the mechanisms differ. Recent evidence also suggests that molecules resulting from reactions between GSNO and H2S, such as thionitrous acid (HSNO), could also have a role in physiology. Taken together, these data suggest important new potential targets for thiol-based drug development

Characterization of the Function of Carbonic Anhydrase 8

Background/Objective: Severe asthma is a complex pulmonary disease characterized by airway inflammation, bronchoconstriction, and acid-base dysregulation. In the Severe Asthma Research Program bronchoscopies, transcriptomics showed CA8 as a gene that is strongly associated with asthma severity. CA8, however, lacks classical CA enzyme function: it does not catalyze hydration and dehydration of CO2. The function of CA8 in the airway epithelium remains unknown. We hypothesize that CA8 serves a protective role in the airway due to its down regulation in patients with severe asthma. We aim to characterize the function of CA8 bystudying its potential as an enzymatic protein. Methods: We used colorimetric assays to detect and quantify nitrogen oxides. We tested for Snitrosothiolsynthase, denitrosylase, nitrate and nitrite synthase, and nitrite reductase activitiesusing the Griess reagent in conjunction with Saville denitrosylation reagents and with reduction using vanadium chloride. Samples were incubated for 60 minutes. We then went on to design ametabolomic experiment in which products will be identified by NMR: for these, we transfected Chinese hamster ovary (CHO) cells using lentivirus containing GFP-labeled CA8 or emptyvector (negative control). Results: CA8 protein does not have these following enzymatic functions: SNO synthase,denitrosylase, nitrite and nitrate synthase, and nitrite reductase. We successfully transfected with GFP-labeled CA8 and are awaiting results of the metabolomic studies. Conclusion and Potential Impact: Isolated CA8 does not appear to have any nitrogen oxideredox activities relevant to asthma. The next steps include confirmatory western and SNOwestern blots to determine protein s-nitrosylation using transfected CHO whole cell lysate. Extracellular medium pH will also be measured. We will then move on to NMR-basedmetabolomics. This will help us better understand the biochemical mechanisms of CA8.Ultimately, this can provide researchers with a novel approach to asthma treatments

HSD3B1 genotype identifies glucocorticoid responsiveness in severe asthma

Asthma resistance to glucocorticoid treatment is a major health problem with unclear etiology. Glucocorticoids inhibit adrenal androgen production. However, androgens have potential benefits in asthma. HSD3B1 encodes for 3β-hydroxysteroid dehydrogenase-1 (3β-HSD1), which catalyzes peripheral conversion from adrenal dehydroepiandrosterone (DHEA) to potent androgens and has a germline missense-encoding polymorphism. The adrenal restrictive HSD3B1(1245A) allele limits conversion, whereas the adrenal permissive HSD3B1(1245C) allele increases DHEA metabolism to potent androgens. In the Severe Asthma Research Program (SARP) III cohort, we determined the association between DHEA-sulfate and percentage predicted forced expiratory volume in 1 s (FEV1PP). HSD3B1(1245) genotypes were assessed, and association between adrenal restrictive and adrenal permissive alleles and FEV1PP in patients with (GC) and without (noGC) daily oral glucocorticoid treatment was determined (n = 318). Validation was performed in a second cohort (SARP I&II; n = 184). DHEA-sulfate is associated with FEV1PP and is suppressed with GC treatment. GC patients homozygous for the adrenal restrictive genotype have lower FEV1PP compared with noGC patients (54.3% vs. 75.1%; P < 0.001). In patients with the homozygous adrenal permissive genotype, there was no FEV1PP difference in GC vs. noGC patients (73.4% vs. 78.9%; P = 0.39). Results were independently confirmed: FEV1PP for homozygous adrenal restrictive genotype in GC vs. noGC is 49.8 vs. 63.4 (P < 0.001), and for homozygous adrenal permissive genotype, it is 66.7 vs. 67.7 (P = 0.92). The adrenal restrictive HSD3B1(1245) genotype is associated with GC resistance. This effect appears to be driven by GC suppression of 3β-HSD1 substrate. Our results suggest opportunities for prediction of GC resistance and pharmacologic intervention

Intentional and unintentional changes to avian and mammalian diversities in the U.K

Rewilding is emerging as a promising restoration strategy to tackle the challenges posed by global change and maintain natural ecosystems and their biodiversity. However, rewilding has also been criticized for the absence of a consistent definition and insufficient knowledge about its possible outcomes. Here, we explored the effects of rewilding on filling functional gaps created by the extirpation of native species. We contrasted rewilding with three other mechanisms for change in community composition—species extirpation, species introduction, and unassisted colonization—in terms of their impacts on changes in avian and mammalian diversity in the UK. We found that (i) while rewilding increases functional diversity most on average, introduced/naturalized birds contribute more functional uniqueness to native functional space than other groups of birds; and (ii) changes in functional diversity associated with “rewilded” organisms were species-dependent and idiosyncratic. Our results suggest that although rewilding can expand or infill native functional trait space to some extent, such effects require careful assessment.

Symbolic Approximation of Weighted Timed Games

Weighted timed games are zero-sum games played by two players on a timed automaton equipped with weights, where one player wants to minimise the accumulated weight while reaching a target. Weighted timed games are notoriously difficult and quickly undecidable, even when restricted to non-negative weights. For non-negative weights, the largest class that can be analysed has been introduced by Bouyer, Jaziri and Markey in 2015. Though the value problem is undecidable, the authors show how to approximate the value by considering regions with a refined granularity. In this work, we extend this class to incorporate negative weights, allowing one to model energy for instance, and prove that the value can still be approximated, with the same complexity. In addition, we show that a symbolic algorithm, relying on the paradigm of value iteration, can be used as an approximation schema on this class

Respiratory Distress in the Newborn with Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is inherited in a predominantly autosomal recessive manner with over 45 currently identified causative genes. It is a clinically heterogeneous disorder that results in a chronic wet cough and drainage from the paranasal sinuses, chronic otitis media with hearing impairment as well as male infertility. Approximately 50% of patients have situs inversus totalis. Prior to the development of chronic oto-sino-pulmonary symptoms, neonatal respiratory distress occurs in more than 80% of patients as a result of impaired mucociliary clearance and mucus impaction causing atelectasis and lobar collapse. Diagnosis is often delayed due to overlapping symptoms with other causes of neonatal respiratory distress. A work up for PCD should be initiated in the newborn with compatible clinical features, especially those with respiratory distress, consistent radiographic findings or persistent oxygen requirement and/or organ laterality defects

Challenging the geographic bias in recognising large-scale patterns of diversity change

Aim: Geographic structure is a fundamental organising principle in ecological and Earth sciences, and our planet is conceptually divided into distinct geographic clusters (e.g. ecoregions and biomes) demarcating unique diversity patterns. Given recent advances in technology and data availability, however, we ask whether geographically clustering diversity time-series should be the default framework to identify meaningful patterns of diversity change. Location: North America. Taxon: Aves. Methods: We first propose a framework that recognises patterns of diversity change based on similarities in the behaviour of diversity time-series, independent of their specific or relative spatial locations. Specifically, we applied an artificial neural network approach, the self-organising map (SOM), to group time-series of over 0.9 million observations from the North American Breeding Birds Survey (BBS) data from 1973 to 2016. We then test whether time-series identified as having similar behaviour are geographically structured. Results: We find little evidence of strong geographic structure in patterns of diversity change for North American breeding birds. The majority of the recognised diversity time-series patterns tend to be indistinguishable from being independently distributed in space. Main Conclusions: Our results suggest that geographic proximity may not correspond to shared temporal trends in diversity; assuming that geographic clustering is the basis for analysis may bias diversity trend estimation. We suggest that approaches that consider variability independently of geographic structure can serve as a useful addition to existing organising rules of biodiversity time-series

Ecosystem service provision by road verges

1. Roads form a vast, rapidly growing global network that has diverse, detrimental ecological impacts. However, the habitats that border roads (‘road verges’) form a parallel network that might help mitigate these impacts and provide additional benefits (ecosystem services; ES). 2. We evaluate the capacity of road verges to provide ES by reviewing existing research and considering their relevant characteristics: area, connectivity, shape, and contextual ES supply and demand. We consider the present situation, and how this is likely to change based on future projections for growth in road extent, traffic densities and urban populations. 3. Road verges not only provide a wide range of ES, including biodiversity provision, regulating services (e.g. air and water filtration) and cultural services (e.g. health and aesthetic benefits by providing access to nature) but also displace other habitats and provide ecosystem disservices (e.g. plant allergens and damage to infrastructure). Globally, road verges may currently cover 270,000 km2 and store 0.015 Gt C/year, which will further increase with 70% projected growth in the global road network. 4. Road verges are well placed to mitigate traffic pollution and address demand for ES in surrounding ES‐impoverished landscapes, thereby improving human health and well‐being in urban areas, and improving agricultural production and sustainability in farmland. Demand for ES provided by road verges will likely increase due to projected growth in traffic densities and urban populations, though traffic pollution will be reduced by technological advances (e.g. electric vehicles). Road verges form a highly connected network, which may enhance ES provision but facilitate the dispersal of invasive species and increase vehicle–wildlife collisions. 5. Synthesis and applications. Road verges offer a significant opportunity to mitigate the negative ecological effects of roads and to address demand for ecosystem services (ES) in urban and agricultural landscapes. Their capacity to provide ES might be enhanced considerably if they were strategically designed and managed for environmental outcomes, namely by optimizing the selection, position and management of plant species and habitats. Specific opportunities include reducing mowing frequencies and planting trees in large verges. Road verge management for ES must consider safety guidelines, financial costs and ecosystem disservices, but is likely to provide long‐term financial returns if environmental benefits are considered