Identification and characterisation of enteroaggregative Escherichia coli subtypes associated with human disease

Enteroaggregative E. coli (EAEC) are a major cause of diarrhoea worldwide. Due to their heterogeneity and carriage in healthy individuals, identification of diagnostic virulence markers for pathogenic strains has been difficult. In this study, we have determined phenotypic and genotypic differences between EAEC strains of sequence types (STs) epidemiologically associated with asymptomatic carriage (ST31) and diarrhoeal disease (ST40). ST40 strains demonstrated significantly enhanced intestinal adherence, biofilm formation, and pro-inflammatory interleukin-8 secretion compared with ST31 isolates. This was independent of whether strains were derived from diarrhoea patients or healthy controls. Whole genome sequencing revealed differences in putative virulence genes encoding aggregative adherence fimbriae, E. coli common pilus, flagellin and EAEC heat-stable enterotoxin 1. Our results indicate that ST40 strains have a higher intrinsic potential of human pathogenesis due to a specific combination of virulence-related factors which promote host cell colonization and inflammation. These findings may contribute to the development of genotypic and/or phenotypic markers for EAEC strains of high virulence

Cinnamyl alcohol oxidation using supported bimetallic Au-Pd nanoparticles: An optimization of metal ratio and investigation of the deactivation mechanism under autoxidation conditions

The aerobic oxidation of cinnamyl alcohol in toluene under autoxidation conditions has been studied using a range of 1 wt% Au–Pd/TiO2 catalysts. The catalysts have been studied to determine the effect of preparation method (impregnation and sol immobilisation) and metal ratio on the conversion of cinnamyl alcohol and the selectivity to cinnamaldehyde. The catalysts prepared by sol-immobilisation demonstrate higher selectivity to the desired aldehyde than the analogous impregnation materials. The most active catalyst was found to be 0.75 wt% Au–0.25 wt% Pd/TiO2 prepared by sol-immobilisation and this demonstrates the importance of metal ratio optimisation in this catalytic process. Furthermore, this metal ratio was found to be most stable under the reactions conditions with little change observed over multiple uses

Three step synthesis of benzylacetone and 4-(4-methoxyphenyl)butan-2-one in flow using micropacked bed reactors

The synthesis of benzylacetone from benzyl alcohol and of 4-(4-methoxyphenyl)butan-2-one from 4-methoxybenzyl alcohol, which were previously performed in a batch cascade, were successfully performed in a telescoped flow system consisting of three micropacked bed reactors and a tube-in-tube membrane to remove oxygen. The system consisted of approximately 10 mg of 1 wt% AuPd/TiO2 catalyst for oxidation, 150-250 mg of anatase TiO2 for C-C coupling and 10 mg of 1 wt% Pt/TiO2 for reduction, operating at 115 °C, 130 °C and 120 °C respectively. Oxygen and hydrogen flowrates were 2 and 1.5 NmL/min and alcohol solution inlet flowrates were 10-80 µL/min, while the system operated at a back pressure of 5 barg. This system achieved significantly increased yields of benzylacetone compared to the batch cascade (56% compared to 8%) and slightly increased yields of 4-(4-methoxyphenyl)butan-2-one (48% compared to 41% when using the same catalyst supports). The major advantage of the telescoped flow system was the ability to separate the three reactions, so that each reaction could have its own catalyst and operating conditions, which led to significant process intensification

The preparation of large surface area lanthanum based perovskite supports for AuPt nanoparticles: tuning the glycerol oxidation reaction pathway by switching the perovskite B site

Gold and gold alloys, in the form of supported nanoparticles, have been shown over the last three decades to be highly effective oxidation catalysts. Mixed metal oxide perovskites, with their high structural tolerance, are ideal for investigating how changes in the chemical composition of supports affect the catalysts' properties, while retaining similar surface areas, morphologies and metal co-ordinations. However, a significant disadvantage of using perovskites as supports is their high crystallinity and small surface area. We report the use of a supercritical carbon dioxide anti-solvent precipitation methodology to prepare large surface area lanthanum based perovskites, making the deposition of 1 wt% AuPt nanoparticles feasible. These catalysts were used for the selective oxidation of glycerol. By changing the elemental composition of the perovskite B site, we dramatically altered the reaction pathway between a sequential oxidation route to glyceric or tartronic acid and a dehydration reaction pathway to lactic acid. Selectivity profiles were correlated to reported oxygen adsorption capacities of the perovskite supports and also to changes in the AuPt nanoparticle morphologies. Extended time on line analysis using the best oxidation catalyst (AuPt/LaMnO3) produced an exceptionally high tartronic acid yield. LaMnO3 produced from alternative preparation methods was found to have lower activities, but gave comparable selectivity profiles to that produced using the supercritical carbon dioxide anti-solvent precipitation methodology

The controlled catalytic oxidation of furfural to furoic acid using AuPd/MgIJ(OH)2

© 2017 The Royal Society of Chemistry. The emphasis of modern chemistry is to satisfy the needs of consumers by using methods that are sustainable and economical. Using a 1% AuPd/Mg(OH) 2 catalyst in the presence of NaOH and under specific reaction conditions furfural; a platform chemical formed from lignocellulosic biomass, can be selectively oxidised to furoic acid, and the catalyst displays promising reusability for this reaction. The mechanism of this conversion is complex with multiple competing pathways possible. The experimental conditions and AuPd metal ratio can be fine-tuned to provide enhanced control of the reaction selectivity. Activation energies were derived for the homogeneous Cannizzaro pathway and the catalytic oxidation of furfural using the initial rates methodology. This work highlights the potential of using a heterogeneous catalyst for the oxidation of furfural to furoic acid that has potential for commercial application

Au-Pd nanoparticles dispersed on composite titania/graphene oxide-supports as a highly active oxidation catalyst

The control over both the dispersion and the particle size distribution of supported precious metal nanoparticles used in heterogeneous catalysts is of paramount importance. Here, we demonstrate the successful formation of highly accessible and well dispersed gold–palladium nanoparticles, stabilized with two-dimensional graphene oxide, that itself is dispersed by intercalated titania particles to form ternary hybrid catalysts. In this application, graphene oxide acts as an effective substitute for the more conventional polymer ligands that are used to stabilize nanoparticles in a sol-immobilization procedure. The particle size distribution can be adjusted by varying the graphene oxide-to-metal mass ratio. The addition of titania efficiently hinders the stacking and agglomeration of the supported metal on graphene oxide sheets, facilitating diffusion of oxygen and reactants to the catalyst surface. This gold–palladium/graphene oxide/titania “ternary” catalyst has been tested for the selective oxidation of a range of alcohols. The resulting optimized catalyst exhibits a comparable activity to a sol-immobilized derived catalyst where the metal nanoparticles are stabilized by poly(vinyl alcohol) ligands, with the graphene oxide-stabilized hybrid catalyst having enhanced stability. We consider that the novel strategy of supporting metal nanoparticles described here can also be adopted to synthesize a wide range of high activity, stable heterogeneous catalysts for other reactions

Meeting the challenges of implementing rapid genomic testing in acute pediatric care

Authors: Stark, Z. Lunke, S. Brett, G. Tan, N. Stapleton, R. Kumble, S. Yeung, A. Phelan, D. Chong, B. Fernandez, M.F. Marum, J.E. Hunter, M. Jarmolowicz, A. Yael Prawer, Y. Riseley, J.R. Regan, M. Elliott, J. Melissa Martyn, M. Best, S. Tan, T. Clara L Gaff, C.L. and White, S.M

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

A first update on mapping the human genetic architecture of COVID-19

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