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.     

Thyroid hormones selectively modulate human alcohol dehydrogenase isozyme catalyzed ethanol oxidation

Thyroid hormones are potent, instantaneous, and reversible inhibitors of ethanol oxidation catalyzed by isozymes of class I and II human alcohol dehydrogenase (ADH). None of the thyroid hormones inhibits class III ADH. At pH 7.40 the apparent Ki values vary between 55 and 110 microM for triiodothyronine, 35 and greater than 200 microM for thyroxine, and 10 and 23 microM for triiodothyroacetic acid. The inhibition is of a mixed type toward both NAD+ and ethanol. The binding of the thyroid hormone triiodothyronine to beta 1 gamma 1 ADH is mutually exclusive with 1,10-phenanthroline, 4-methylpyrazole, and testosterone, identifying a binding site(s) for the thyroid hormones, which overlap(s) both the 1,10-phenanthroline site near the active site zinc atom and the testosterone binding site, the latter being a regulatory site on the gamma-subunit-containing isozymes and distinct from their catalytic site. The inhibition by thyroid hormones may have implications for regulation of ADH catalysis of ethanol and alcohols in the intermediary metabolism of dopamine, norepinephrine, and serotonin and in steroid metabolism. In concert with other hormonal regulators, e.g., testosterone, the rate of ADH catalysis is capable of being fine tuned in accord with both substrate and modulator concentrations.     

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.