Elucidation of insulin assembly at acidic and neutral pH: Characterization of low molecular weight oligomers

Deficiency in insulin secretion and function that characterize type 2 diabetes often requires administration of extraneous insulin, leading to injection‐site amyloidosis. Insulin aggregation at neutral pH is not well understood. Although oligomer formation is believed to play an important role, insulin oligomers have not been fully characterized yet. Here, we elucidate similarities and differences between in vitro insulin aggregation at acidic and neutral pH for a range of insulin concentrations (2.5–100 μM) by using kinetic thioflavin T fluorescence, circular dichroism, atomic force and electron microscopy imaging. Importantly, we characterize the size distribution of insulin oligomers at different assembly stages by the application of covalent cross‐linking and gel electrophoresis. Our results show that at the earliest assembly stage, oligomers comprise up to 40% and 70% of soluble insulin at acidic and neutral pH, respectively. While the highest oligomer order increases with insulin concentration at acidic pH, the opposite tendency is observed at neutral pH, where oligomers up to heptamers are formed in 10 μM insulin. These findings suggest that oligomers may be on‐ and off‐pathway assemblies for insulin at acidic and neutral pH, respectively. Agitation, which is required to induce insulin aggregation at neutral pH, is shown to increase fibril formation rate and fibrillar mass both by an order of magnitude. Insulin incubated under agitated conditions at neutral pH rapidly aggregates into large micrometer‐sized aggregates, which may be of physiological relevance and provides insight into injection‐site amyloidosis and toxic pulmonary aggregates induced by administration of extraneous insulin.     

Niche evolution and diversification in a Neotropical radiation of birds (Aves: Furnariidae)

Rapid diversification may be caused by ecological adaptive radiation via niche divergence. In this model, speciation is coupled with niche divergence and lineage diversification is predicted to be correlated with rates of niche evolution. Studies of the role of niche evolution in diversification have generally focused on ecomorphological diversification but climatic‐niche evolution may also be important. We tested these alternatives using a phylogeny of 298 species of ovenbirds (Aves: Furnariidae). We found that within Furnariidae, variation in species richness and diversification rates of subclades were best predicted by rate of climatic‐niche evolution than ecomorphological evolution. Although both are clearly important, univariate regression and multivariate model averaging more consistently supported the climatic‐niche as the best predictor of lineage diversification. Our study adds to the growing body of evidence, suggesting that climatic‐niche divergence may be an important driver of rapid diversification in addition to ecomorphological evolution. However, this pattern may depend on the phylogenetic scale at which rate heterogeneity is examined.     

QTL mapping of root traits in phosphorus-deficient soils reveals important genomic regions for improving NDVI and grain yield in barley

Key message

Major QTLs for root rhizosheath size are not correlated with grain yield or yield response to phosphorus. Important QTLs were found to improve phosphorus efficiency.

Abstract

Root traits are important for phosphorus (P) acquisition, but they are often difficult to characterize and their breeding values are seldom assessed under field conditions. This has shed doubts on using seedling-based criteria of root traits to select and breed for P efficiency. Eight root traits were assessed under controlled conditions in a barley doubled-haploid population in soils differing in P levels. The population was also phenotyped for grain yield, normalized difference vegetation index (NDVI), grain P uptake and P utilization efficiency at maturity (PutE_GY) under field conditions. Several quantitative traits loci (QTLs) from the root screening and the field trials were co-incident. QTLs for root rhizosheath size and root diameter explained the highest phenotypic variation in comparison to QTLs for other root traits. Shared QTLs were found between root diameter and grain yield, and total root length and PutE_GY. A common major QTL for rhizosheath size and NDVI was mapped to the HvMATE gene marker on chromosome 4H. Collocations between major QTLs for NDVI and grain yield were detected on chromosomes 6H and 7H. When results from BIP and MET were combined, QTLs detected for grain yield were also those QTLs found for NDVI. QTLs qGY5H, qGY6H and qGY7Hb on 7H were robust QTLs in improving P efficiency. A selection of multiple loci may be needed to optimize the breeding outcomes due to the QTL x Environment interaction. We suggest that rhizosheath size alone is not a reliable trait to predict P efficiency or grain yield.

     

Whole‐landscape modelling of compositional turnover in aquatic invertebrates informs conservation gap analysis: An example from south‐western Australia

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