The distribution of carbohydrate side chains along the polypeptide chain of glucoamylase

Glucoamylase is a starch-hydrolyzing enzyme with a glycoprotein structure, used industrially for the conversion of starch to glucose, citric acid, corn syrups, and high-fructose sweeteners. This enzyme possesses an unusual type of structure in which many carbohydrate side chains are linked O-glycosidically to serine and threonine residues of the polypeptide chain. The carbohydrate side chains may be single monosaccharide residues or oligosaccharides of mannose, glucose, galactose, and in some cases N-acetylglucosamine. New data from experiments on the CNBr fragmentation of glucoamylase followed by chemical and immunological characterization of the fragments show that the carbohydrate side chains are distributed randomly along the polypeptide chain. Such a structure is appropriately termed a random model reprensentation for the glucoamylase molecule.     

Biological and structural properties of MIP-1 alpha expressed in yeast.

The murine macrophage inflammatory proteins-1 alpha (MIP-1 alpha) and MIP-1 beta are distinct but closely related cytokines. Partially purified mixtures of the two proteins affect neutrophil function and cause local inflammation and fever. The particular properties of MIP-1 alpha have not been well studied, although it has been identified as being identical to an inhibitor of haemopoietic stem cell growth. We have expressed MIP-1 alpha in yeast cells and purified it to sequence homogeneity. Structural analysis of this biologically active material by circular dichroism and fluorescence spectroscopy confirms that MIP-1 alpha has a very similar secondary and tertiary structure to platelet factor 4 and interleukin 8 with which it shares limited sequence homology. The in-vitro stem cell inhibitory properties have been confirmed using a range of murine progenitor cells including purified bone marrow progenitor cells (FACS-1), the FDCP-mix A4 cell line, and spleen colony forming unit (CFU-S) populations. Plateau levels of inhibition of stem cell growth were achieved using concentrations of 0.15 micrograms/ml MIP-1 alpha. We have also demonstrated that MIP-1 alpha is active in vivo: 5 micrograms of MIP-1 alpha per mouse given as a bolus injection, protects stem cells from subsequent in-vitro killing by tritiated thymidine. MIP-1 alpha was also shown to enhance the proliferation of more committed progenitor granulocyte macrophage-colony forming cells (GM-CFC) in response to granulocyte macrophage-colony stimulating factor (GM-CSF).     

A sticky situation: CCN1 promotes both proliferation and apoptosis of cancer cells

Connective tissue growth factor (CTGF/CCN2) is overexpressed in diabetes. Diabetic rats possess myocardial and cardiomyocyte hypertrophy. In a recent report, Wang and colleagues (Am J Physiol Cell Physiol. 2009 Jul 22. [Epub ahead of print]) show that CCN2 directly mediates cardiomyocyte hypertrophy as well as that induced by high glucose and fatty acid. CCN2 acted via the TrkA receptor. These data are the subject of this commentary, and emphasize that CCN2 may be an excellent target for therapy in diabetes.     

The twin threshold model: risk-intermediate foraging by rufous hummingbirds, Selasphorus rufus

I developed two versions of the twin threshold model (TTM) to assess risk-sensitive foraging decisions by rufous hummingbirds. The model incorporates energy thresholds for both starvation and reproduction and assesses how three reward distributions with a common mean but different levels of variance interact with these critical thresholds to determine fitness. Fitness, a combination of survival and reproduction, is influenced by both the amount of variance in the distributions and the relative position of the common mean between the thresholds. The model predicts that risk-intermediate foraging is often the optimal policy, and that risk aversion is favoured as the common mean of the distributions approaches the starvation threshold, whereas risk preference is favoured as the common mean approaches the reproduction threshold. Tests with free-living hummingbirds supported these predictions. Hummingbirds were presented with three distributions of nectar rewards that had a common mean but Nil, Moderate or High levels of variance. Birds preferred intermediate levels of variance (Moderate) when presented with all three rewards simultaneously, and became more risk-averse as the mean of the distributions was decreased but more risk-prone as the mean was increased. Birds preferred Nil when it was paired with Moderate or with High, but preferred Moderate in the presence of Nil and High together. This reversal of preference is a violation of regularity, conventionally interpreted as irrational choice behaviour. I provide an alternative version of the TTM demonstrating that violations of regularity can occur when relative instead of absolute evaluation mechanisms are used.