Novel C-terminal gastrin antagonists. Synthesis and biological activity

The C-terminal tetrapeptide, Trp-Met-Asp-Phe-NH2, is a full agonist of gastrin, but des-Phe analogues, including Boc-Trp-Met-Asp-NH2, are antagonists. To ascertain the minimum structural requirement for an antagonist, we used conventional solution phase methodology to synthesize analogues with further modifications including removal of the alpha-amino group of Trp, conversion of the indole to a phenyl ring, and methylation of amide bonds. These analogues were tested for their effect on pentagastrin-stimulated acid release in dogs surgically prepared with a gastric fistula. When infused intravenously at a dose of 20 pmol kg-1 h-1, the peptides significantly inhibited acid secretion. The extent of inhibition ranged from 12% to 60%. Thus, tripeptide analogues based on the C-terminal sequence of gastrin act as potent and specific antagonists of gastrin-stimulated acid secretion.     

Inactivation of E. coli in Cranberry Juice by a High Voltage Pulsed Electric Field

The aim of this work was to study the effect of a high voltage pulsed electric field (PEF) on the inactivation of E. coli in cranberry juice to achieve the regulatory requirement of a 5‐log reduction in the microbial count. PEF processing involved the application of high voltage pulses to liquid or semi‐solid materials, placed between two electrodes at ambient, sub‐ambient, or supra‐ambient temperature. In this work, cranberry juice, inoculated with E. coli was subjected to 60 pulses in the voltage range of 5 to 40 kV/cm. The experiments were carried out at 20 °C. The temperature rise was less than 2 °C at the average treatment time of 80 s. PEF is an emerging non‐thermal technology for food preservation that retains the natural taste of food. It has mainly been applied to improve the shelf life of such foods as milk, liquid eggs and fruit juices.     

Temporal Variation in Decisions about Parental Care in Bluegill, Lepomis macrochirus

Parental investment theory states that an individual will trade‐off present and future reproductive potential to maximize lifetime reproductive success. Only when parental care is costly in terms of reduced future reproductive potential should individuals be sensitive to changes in the value of current offspring and adjust their care. Here, we examine temporal variation in parental care decision‐making in bluegill (Lepomis macrochirus), in which care is provided by males called ‘parentals’. Previous research has shown that parentals that nest early in the breeding season are in higher energetic condition than those that nest later, and early nesting males appear not to pay an opportunity cost to their care in terms of reduced future reproductive potential. Early nesting males also may have higher paternity in their broods than later nesting males. To examine the parental care decisions made by early and mid‐season nesting parentals, we experimentally reduced males’ perceived paternity by swapping eggs between nests. We found that experimental males that nested early in the breeding season adjusted their brood defence behaviour similarly to control males, which had sham egg swaps performed. Conversely, experimental males that nested mid‐season significantly decreased their brood defence behaviour after the manipulation as compared with control males. Thus, unlike mid‐season nesting males, early nesting males appear relatively insensitive to changes in brood value (paternity), possibly because early nesting males pay little cost in terms of reduced future reproductive potential to providing full care or because these males have a predisposition to high paternity.     

The Arg92Cys colipase polymorphism impairs function and secretion by increasing protein misfolding

Colipase is essential for efficient fat digestion. An arginine-to-cysteine polymorphism at position 92 of colipase (Arg92Cys) associates with an increased risk for developing type-2 diabetes through an undefined mechanism. To test our hypothesis that the extra cysteine increases colipase misfolding, thereby altering its intracellular trafficking and function, we expressed Cys92 colipase in HEK293T cells. Less Cys92 colipase is secreted and more is retained intracellularly in an insoluble form compared with Arg92 colipase. Nonreducing gel electrophoresis suggests the folding of secreted Cys92 colipase differs from Arg92 colipase. Cys92 colipase misfolding does not trigger the unfolded protein response (UPR) or endoplasmic reticulum (ER) stress. The ability of secreted Cys92 colipase to stimulate pancreatic triglyceride lipase (PTL) is reduced with all substrates tested, particularly long-chain triglycerides. The reaction of Cys92 colipase with triolein and Intralipid has a much longer lag time, reflecting decreased ability to anchor PTL on those substrates. Our data predicts that humans with the Arg92Cys substitution will secrete less functional colipase into the duodenum and have less efficient fat digestion. Whether inefficient fat digestion or another property of colipase contributes to the risk for developing diabetes remains to be clarified.     

Foreword: Protein acylation and microdomains in membrane function

The Signal Recognition Particle (SRP) plays a critical role in the sorting of nascent secretory and membrane proteins. Remarkably, this function has been conserved from bacteria, where SRP delivers proteins to the inner membrane, through to eukaryotes, where SRP is required for targeting of proteins to the endoplasmic reticulum. This review focuses on present understanding of SRP structure and function and the relationship between the two. Furthermore, the similarities and differences in the structure, function and cellular role of SRP in bacteria, chloroplasts, fungi and mammals will be stressed.