Hummingbird flight: sustaining the highest mass-specific metabolic rates among vertebrates.

Resting and maximal mass-specific metabolic rates scale inversely with body mass. Small hummingbirds achieve the highest known mass-specific metabolic rates among vertebrate homeotherms. Maximal capacities for O2 and substrate delivery to muscle mitochondria, as well as mitochondrial oxidative capacities in these animals may be at the upper limits of what are structurally and functionally possible given the constraints inherent in vertebrate design. Such constraints on the evolutionary design of functional capacities may play an important role in determining the lower limits to vertebrate homeotherm size and the upper limits to mass-specific metabolic rate.     

Allometric cascade as a unifying principle of body mass effects on metabolism

The power function of basal metabolic rate scaling is expressed as aM(b), where a corresponds to a scaling constant (intercept), M is body mass, and b is the scaling exponent. The 3/4 power law (the best-fit b value for mammals) was developed from Kleiber's original analysis and, since then, most workers have searched for a single cause to explain the observed allometry. Here we present a multiple-causes model of allometry, where the exponent b is the sum of the influences of multiple contributors to metabolism and control. The relative strength of each contributor, with its own characteristic exponent value, is determined by the control contribution. To illustrate its use, we apply this model to maximum versus basal metabolic rates to explain the differing scaling behaviour of these two biological states in mammals. The main difference in scaling is that, for the basal metabolic rate, the O(2) delivery steps contribute almost nothing to the global b scaling exponent, whereas for the maximum metabolic rate, the O(2) delivery steps significantly increase the global b value.     

Hummingbird flight: Sustaining the highest mass-specific metabolic rates among vertebrates

Resting and maximal mass-specific metabolic rates scale inversely with body mass. Small hummingbirds achieve the highest known mass-specific metabolic rates among vertebrate homeotherms. Maximal capacities for O₂ and substrate delivery to muscle mitochondria, as well as mitochondrial oxidative capacities in these animals may be at the upper limits of what are structurally and functionally possible given the constraints inherent in vertebrate design. Such constraints on the evolutionary design of functional capacities may play an important role in determining the lower limits to vertebrate homeotherm size and the upper limits to mass-specific metabolic rate.     

A VEGF-A splice variant defective for heparan sulfate and neuropilin-1 binding shows attenuated signaling through VEGFR-2

The development of functional blood and lymphatic vessels requires spatio-temporal coordination of the production and release of growth factors such as vascular endothelial growth factors (VEGFs). VEGF family proteins are produced in multiple isoforms with distinct biological properties and bind to three types of VEGF receptors. A VEGF-A splice variant, VEGF-A₁₆₅b, has recently been isolated from kidney epithelial cells. This variant is identical to VEGF-A₁₆₅ except for the last six amino acids encoded by an alternative exon. VEGF-A₁₆₅b and VEGF-A₁₆₅ bind VEGF receptors 1 and 2 with similar affinity. VEGF-A₁₆₅b elicits drastically reduced activity in angiogenesis assays and even counteracts signaling by VEGF-A₁₆₅. VEGF-A₁₆₅b weakly binds to heparan sulfate and does not interact with neuropilin-1, a coreceptor for VEGF receptor 2. To determine the molecular basis for altered signaling by VEGF-A₁₆₅b we measured VEGF receptor 2 and ERK kinase activity in endothelial cells in culture. VEGF-A₁₆₅ induced strong and sustained activation of VEGF receptor 2 and ERK-1 and −2, while activation by VEGF-A₁₆₅b was only weak and transient. Taken together these data show that VEGF-A₁₆₅b has attenuated signaling potential through VEGF receptor 2 defining this new member of the VEGF family as a partial receptor agonist. Received 31 May 2006; received after revision 26 June 2006; accepted 14 July 2006