Irisin and FNDC5 in retrospect: An exercise hormone or a transmembrane receptor?

FNDC5 (fibronectin domain-containing [protein] 5) was initially discovered and characterized by two groups in 2002. In 2011 FNDC5 burst into prominence as the parent of irisin, a small protein containing the fibronectin type III domain. Irisin was proposed to be secreted by skeletal muscle cells in response to exercise, and to circulate to fat tissue where it induced a transition to brown fat. Since brown fat results in dissipation of energy, this pathway is of considerable interest for metabolism and obesity. Here I review the original discoveries of FNDC5 and the more recent discovery of irisin. I note in particular three problems in the characterization of irisin: the antibodies used to detect irisin in plasma lack validity; the recombinant protein used to demonstrate activity in cell culture was severely truncated; and the degree of shedding of soluble irisin from the cell surface has not been quantitated. The original discovery proposing that FNDC5 may be a transmembrane receptor may deserve a new look.

Invariant measure selection by noise. An example

We consider a deterministic system with two conserved quantities and infinity many invariant measures. However the systems possess a unique invariant measure when enough stochastic forcing and balancing dissipation are added. We then show that as the forcing and dissipation are removed a unique limit of the deterministic system is selected. The exact structure of the limiting measure depends on the specifics of the stochastic forcing.

Local kinetic interpretation of entropy production through reversed diffusion.

The time reversal of stochastic diffusion processes is revisited with emphasis on the physical meaning of the time-reversed drift and the noise prescription in the case of multiplicative noise. The local kinematics and mechanics of free diffusion are linked to the hydrodynamic description. These properties also provide an interpretation of the Pope-Ching formula for the steady-state probability density function along with a geometric interpretation of the fluctuation-dissipation relation. Finally, the statistics of the local entropy production rate of diffusion are discussed in the light of local diffusion properties, and a stochastic differential equation for entropy production is obtained using the Girsanov theorem for reversed diffusion. The results are illustrated for the Ornstein-Uhlenbeck process.

Peptide interfacial biomaterials improve endothelial cell adhesion and spreading on synthetic polyglycolic acid materials.

Resorbable scaffolds such as polyglycolic acid (PGA) are employed in a number of clinical and tissue engineering applications owing to their desirable property of allowing remodeling to form native tissue over time. However, native PGA does not promote endothelial cell adhesion. Here we describe a novel treatment with hetero-bifunctional peptide linkers, termed "interfacial biomaterials" (IFBMs), which are used to alter the surface of PGA to provide appropriate biological cues. IFBMs couple an affinity peptide for the material with a biologically active peptide that promotes desired cellular responses. One such PGA affinity peptide was coupled to the integrin binding domain, Arg-Gly-Asp (RGD), to build a chemically synthesized bimodular 27 amino acid peptide that mediated interactions between PGA and integrin receptors on endothelial cells. Quartz crystal microbalance with dissipation monitoring (QCMD) was used to determine the association constant (K (A) 1 x 10(7) M(-1)) and surface thickness (~3.5 nm). Cell binding studies indicated that IFBM efficiently mediated adhesion, spreading, and cytoskeletal organization of endothelial cells on PGA in an integrin-dependent manner. We show that the IFBM peptide promotes a 200% increase in endothelial cell binding to PGA as well as 70-120% increase in cell spreading from 30 to 60 minutes after plating.

Observations of spatial flow patterns at the coral colony scale on a shallow reef flat

Although small-scale spatial flow variability can affect both larger-scale circulation patterns and biological processes on coral reefs, there are few direct measurements of spatial flow patterns across horizontal scales <100 m. Here flow patterns on a shallow reef flat were measured at scales from a single colony to several adjacent colonies using an array of acoustic Doppler velocimeters on a diver-operated traverse. We observed recirculation zones immediately behind colonies, reduced currents and elevated dissipation rates in turbulent wakes up to 2 colony diameters downstream and enhanced Reynolds stresses in shear layers around wake peripheries. Flow acceleration zones were observed above and between colonies. Coherent flow structures varied with incident flow speeds; recirculation zones were stronger and wakes were more turbulent in faster flows. Low-frequency (<0.03 Hz) flow variations, for which water excursions were large compared with the colony diameters (Keulegan-Carpenter number, KC >1), had similarspatial patterns to wakes, while higher-frequency variations (0.05-0.1 Hz, KC<1) had no observable spatial structure. On the reef flat, both drag and inertial forces exerted by coral colonies could have significant effects on flow, but within different frequency ranges; drag dominates for low-frequency flow variations and inertial forces dominate for higher frequency variations, including the wave band. Our scaling analyses suggest that spatial flow patterns at colony and patch scales could have important implications or both physical and biological processes at larger reef scales through their effects on forces exerted on the flow, turbulent mixing, and dispersion. © 2013. American Geophysical Union. All Rights Reserved.