A Selective Irreversible Inhibitor of Furin Does Not Prevent Pseudomonas Aeruginosa Exotoxin A-Induced Airway Epithelial Cytotoxicity

Many bacterial and viral pathogens (or their toxins), including Pseudomonas aeruginosa exotoxin A, require processing by host pro-protein convertases such as furin to cause disease. We report the development of a novel irreversible inhibitor of furin (QUB-F1) consisting of a diphenyl phosphonate electrophilic warhead coupled with a substrate-like peptide (RVKR), that also includes a biotin tag, to facilitate activity-based profiling/visualisation. QUB-F1 displays greater selectivity for furin, in comparison to a widely used exemplar compound (furin I) which has a chloromethylketone warhead coupled to RVKR, when tested against the serine trypsin-like proteases (trypsin, prostasin and matriptase), factor Xa and the cysteine protease cathepsin B. We demonstrate QUB-F1 does not prevent P. aeruginosa exotoxin A-induced airway epithelial cell toxicity; in contrast to furin I, despite inhibiting cell surface furin-like activity to a similar degree. This finding indicates additional proteases, which are sensitive to the more broad-spectrum furin I compound, may be involved in this process

Short Life Working Group on Facilitating Peaceful Assemblies: report

The Short Life Working Group on Peaceful Processions in Scotland has reviewed processions in Scotland. The report uses the comparison between Northern Ireland and Scotland as a basis to discuss how well the legislative framework and related processes are working in Scotland

Photocatalytic air-purification: A low-cost, real-time gas detection method

This research demonstrates the use of a gas detector as a feasible alternative to the standardized analytical methods typically found in photocatalytic air-purification ISO standard tests and academic literature. A methyl mercaptan detector is calibrated and validated (for linearity) using a standard gas generator. The detector can be directly connected to the photoreactor exit allowing real-time span gas measurement with data-logging at one minute intervals. The detector successfully differentiated samples with different photocatalytic performance. The use of such detectors offers an easy-to-use, low-cost alternative to gas measurement with applications in academic research, proof-of-concept photocatalytic tests and also as an educational tool

Current efforts on microplastic monitoring in Arctic fish and how to proceed

In this review, we investigated published data on the occurrence of microplastic in Arctic fish, and the suitability of the data and species for risk assessment and monitoring. As of 11.11.2021, we found nine studies in the peer-reviewed literature, one thesis and one report, confirming the occurrence of microplastic in fishes from multiple Arctic regions. The studies varied in methodology, detection and quantification limitations, reported categories of size, shape, and chemical identity. All these factors influence the numbers of microplastic reported, thus limiting comparability and hindering integrative analysis. The physiological impacts of the reported microplastic contamination cannot be determined, as all studies targeted stomach/intestine contents and did not use methods with limits of detection low enough to determine particle translocation from the intestine to other organs, tissues or body fluids within the fish. Furthermore, there is a fundamental lack of understanding the transfer and the effects of plastic additives to Arctic fishes. In addition to discussing methodological challenges and knowledge gaps, we consider ecosystem needs, commercial interests, Indigenous people’s subsistence, food safety and food sovereignty concerns, and developed a framework to harmonize and facilitate pan-Arctic microplastic monitoring.Current efforts on microplastic monitoring in Arctic fish and how to proceedacceptedVersio

Genetic mixed stock analysis of an interceptory Atlantic salmonfishery in the Northwest Atlantic

Interceptory fisheries represent an ongoing threat to migratory fish stocks particularly when managed in the absence of stock specific catch and exploitation information. Atlantic salmon from the southern portion of the North American range may be subject to exploitation in the commercial and recreational salmon fisheries occurring in the French territorial waters surrounding St. Pierre and Miquelon off southern Newfoundland. We evaluated stock composition of Atlantic salmon harvested in the St. Pierreand Miquelon Atlantic salmon fishery using genetic mixture analysis and individual assignment with a microsatellite baseline (15 loci, 12,409 individuals, 12 regional groups) encompassing the species western Atlantic range. Individual salmon were sampled from the St. Pierre and Miquelon fishery over four years (2004, 2011, 2013, and 2014). Biological characteristics indicate significant variation among years in the size and age distribution. Nonetheless, estimates of stock composition of the samples showed consistent dominance of three regions (i.e., Southern Gulf of St. Lawrence, Gaspe Peninsula, and New-foundland). Together salmon from these regions accounted for more than 70% of annual harvest over the decade examined. Comparison of individual assignments and biological characteristics revealed a trend of declining fresh water age with latitude of assigned region. Moreover, locally harvested Newfoundland salmon were ten times more likely to be small or one sea winter individuals whereas Quebec and Gaspe Peninsula salmon were two-three times more likely to be harvested as large or two sea winter salmon.Estimates of region specific catch were highest for salmon from the southern Gulf of St. Lawrence region ranging from 242 to 887 individuals annually. This work illustrates how genetic analysis of interceptory marine fisheries can directly inform assessment and management efforts in highly migratory marines pecies

Temporal dynamics of genetic clines of invasive European green crab (Carcinus maenas) in eastern North America

Evolutionary Applications published by John Wiley & Sons Ltd. Reproduced with the permission of the Minister of Fisheries and Oceans Canada. Two genetically distinct lineages of European green crabs (Carcinus maenas) were independently introduced to eastern North America, the first in the early 19th century and the second in the late 20th century. These lineages first came into secondary contact in southeastern Nova Scotia, Canada (NS), where they hybridized, producing latitudinal genetic clines. Previous studies have documented a persistent southward shift in the clines of different marker types, consistent with existing dispersal and recruitment pathways. We evaluated current clinal structure by quantifying the distribution of lineages and fine-scale hybridization patterns across the eastern North American range (25 locations, ~39 to 49°N) using informative single nucleotide polymorphisms (SNPs; n = 96). In addition, temporal changes in the genetic clines were evaluated using mitochondrial DNA and microsatellite loci (n = 9–11) over a 15-year period (2000–2015). Clinal structure was consistent with prior work demonstrating the existence of both northern and southern lineages with a hybrid zone occurring between southern New Brunswick (NB) and southern NS. Extensive later generation hybrids were detected in this region and in southeastern Newfoundland. Temporal genetic analysis confirmed the southward progression of clines over time; however, the rate of this progression was slower than predicted by forecasting models, and current clines for all marker types deviated significantly from these predictions. Our results suggest that neutral and selective processes contribute to cline dynamics, and ultimately, highlight how selection, hybridization, and dispersal can collectively influence invasion success

Array comparative genomic hybridisation-based identification of two imbalances of chromosome 1p in a 9-year-old girl with a monosomy 1p36 related phenotype and a family history of learning difficulties: a case report

<p>Abstract</p> <p>Introduction</p> <p>Monosomy 1p36 is one of the most common terminal deletion syndromes, with an approximate incidence of 1 in every 5000 live births. This syndrome is associated with several pronounced clinical features including characteristic facial features, cardiac abnormalities, seizures and mental retardation, all of which are believed to be due to haploinsufficiency of genes within the 1p36 region. The deletion size varies from approximately 1.5 Mb to 10 Mb with the most common breakpoints located at 1p36.13 to 1p36.33. Over 70% of 1p36 deletion patients have a true terminal deletion. A further 7% have interstitial deletions and a proportion have a derivative chromosome 1 where the 1p telomere is replaced by material from another chromosome, either as a result of a de-novo rearrangement or as a consequence of malsegregation of a balanced parental translocation at meiosis.</p> <p>Case presentation</p> <p>Array comparative genomic hybridisation analysis of a 9-year-old Caucasian girl presenting with dysmorphic facial features and learning difficulties, for whom previous routine karyotyping had been normal, identified two submicroscopic rearrangements within chromosome 1p. Detection of both an insertional duplication of a region of 1p32.3 into the subtelomeric region of the short arm of a chromosome 1 homologue and a deletion within 1p36.32 of the same chromosome instigated a search for candidate genes within these regions which could be responsible for the clinical phenotype of the patient. Several genes were identified by computer-based annotation, some of which have implications in neurological and physical development.</p> <p>Conclusion</p> <p>Array comparative genomic hybridisation is providing a robust method for pinpointing regions of candidate genes associated with clinical phenotypes that extend beyond the resolution of the light microscope. This case report provides an example of how this method of analysis and the subsequent reporting of findings have proven useful in collaborative efforts to elucidate multiple gene functions from a clinical perspective.</p

The impact of parenthood on environmental attitudes and behaviour: a longitudinal investigation of the legacy hypothesis

Willingness to engage in sustainable actions may be limited by the psychological distance of climate change. In this study, we test the legacy hypothesis, which holds that having children leads parents to consider the legacy left to offspring in respect of environmental quality. Using the Understanding Society dataset, a longitudinal survey representative of the UK population (n = 18,176), we assess how having children may change people’s individual environmental attitudes and behaviour. Results indicate that having a new child is associated with a small decrease in the frequency of a few environmental behaviours. Only parents with already high environmental concern show a small increase in the desire to act more sustainably after the birth of their first child. Overall, the results do not provide evidence in support of the legacy hypothesis in terms of individual-level environmental attitudes and behaviours. We argue that the transition to parenthood is a time where concern is prioritised on the immediate wellbeing of the child and not on the future environmental threats

The flesh of painting: Caillebotte’s Modern Olympia

The language of putrefaction, often applied through a culinary analogy, appeared consistently in the critical reception of modern-life and Impressionist painting. For example, two critics used the term faisandé, referring to well-hung meat, to describe Manet’s nude figure of Olympia in 1865. The analogies that they posed between morgue bodies, female figures, meat, and fleshy paint material became central modes of denigrating Impressionist paintings of women in the ensuing decades. Gustave Caillebotte’s Veal in a Butcher’s Shop (c. 1882), depicting anthropomorphized, gendered, and sexualized animal flesh, can be considered in this context. In my reading, the painting enacts the critical responses to his colleagues’ figures, foregrounding the violent operations through which bodies might be reduced to meat, whether literal or metaphorical. In their comparisons to rotting flesh, nineteenth-century critics expressed a visceral reaction to works of art that Veal in a Butcher’s Shop demands