Aims/hypothesis Morphological changes that occur during pancreatic endocrine cell differentiation have been shown in rodent systems to be dependent on sequential alterations in transcription factor expression. However, similar data for humans have been limited. The aim of the present study was to provide a connection between pancreatic morphology, transcription factor gene expression and protein localisation during human fetal development. Methods Human fetal pancreases were examined at early (8-12 weeks of fetal age), middle (14-16 weeks) and late (19-21 weeks) stages, using immunohistological, microarray and qRT-PCR analyses. Results We observed a significant decrease in pancreatic duodenal homeobox 1 (PDX-1) + /cytokeratin 19 + cells (p<0.001), with a simultaneous increase in PDX-1 + /insulin + cells from 8 to 21 weeks (p<0.05). Increased PDX-1/ insulin co-localisation within islet clusters was noted, while no co-expression of PDX-1 with glucagon was found, suggesting that loss of PDX-1 is essential for alpha cell formation. Given that neurogenin 3 (NGN3) expression is critical for establishing the endocrine cell programme in the rodent pancreas, we examined its expression pattern and colocalisation in PDX-1 + , insulin + and glucagon + cells. Colocalisation of NGN3 with PDX-1, insulin and glucagon was noted during early development, with significant decreases in middle and late stages (p<0.001). Our microarray and co-localisation analyses of transcription factors linked to NGN3 demonstrated that ISL1 transcription factor (ISL1), neurogenic differentiation 1 (NEUROD1), NK2 related transcription factor related, locus 2 (NKX2-2) and paired box gene 6 (PAX6) were upregulated during development and present in all four endocrine cell types, while NK6 related transcription factor related, locus 1 (NKX6-1) was expressed exclusively in beta cells. Conclusions/interpretation This study is an important step towards identifying key molecular factors involved in development of the human fetal endocrine pancreas.
The electrochemical reduction of carbon monoxide is a promising approach for the renewable production of carbon-based fuels and chemicals. Copper shows activity toward multi-carbon products from CO reduction, with reaction selectivity favoring two-carbon products; however, efficient conversion of CO to higher carbon products such as n-propanol, a liquid fuel, has yet to be achieved. We hypothesize that copper adparticles, possessing a high density of under-coordinated atoms, could serve as preferential sites for n-propanol formation. Density functional theory calculations suggest that copper adparticles increase CO binding energy and stabilize two-carbon intermediates, facilitating coupling between adsorbed *CO and two-carbon intermediates to form three-carbon products. We form adparticle-covered catalysts in-situ by mediating catalyst growth with strong CO chemisorption. The new catalysts exhibit an n-propanol Faradaic efficiency of 23% from CO reduction at an n-propanol partial current density of 11 mA cm−2.
A high density of homogeneously dispersed atomic defects has long been believed to be a promising strategy for improving catalytic activity. Taking the defective nature of quantum dots, Liu et al. synthesize vacancy-rich metal nanocrystals through in situ electrochemical reduction of quantum dots. This maximizes the density and stability of vacancies in metallic nanocrystals and achieves record current densities with high faradic efficiencies in the electrosynthesis of formate, carbon monoxide, and ethylene at low applied potentials.
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