ER/K linked GPCR-G protein fusions systematically modulate second messenger response in cells.

FRET and BRET approaches are well established for detecting ligand induced GPCR-G protein interactions in cells. Currently, FRET/BRET assays rely on co-expression of GPCR and G protein, and hence depend on the stoichiometry and expression levels of the donor and acceptor probes. On the other hand, GPCR-G protein fusions have been used extensively to understand the selectivity of GPCR signaling pathways. However, the signaling properties of fusion proteins are not consistent across GPCRs. In this study, we describe and characterize novel sensors based on the Systematic Protein Affinity Strength Modulation (SPASM) technique. Sensors consist of a GPCR and G protein tethered by an ER/K linker flanked by FRET probes. SPASM sensors are tested for the β2-, α1-, and α2- adrenergic receptors, and adenosine type 1 receptor (A1R), tethered to Gαs-XL, Gαi2, or Gαq subunits. Agonist stimulation of β2-AR and α2-AR increases FRET signal comparable to co-expressed FRET/BRET sensors. SPASM sensors also retain signaling through the endogenous G protein milieu. Importantly, ER/K linker length systematically tunes the GPCR-G protein interaction, with consequent modulation of second messenger signaling for cognate interactions. SPASM GPCR sensors serve the dual purpose of detecting agonist-induced changes in GPCR-G protein interactions, and linking these changes to downstream signaling

Volume changes in solids induced by chemical alteration

It is a fundamental issue in material science to understand the mechanical effects of chemical alterations. Often the replacement of one chemical component by another in a solid induces local volume changes. Experiments on chemical alteration in “model” materials reveal an intricate dynamics of elastic stress build-up, fracturing and creation of porosity. In that way permeability is increased and provides a positive feedback on the process rate. Important examples from geology are presented

Experimental pressure solution compaction of synthetic halite/calcite aggregates.

Experimental observations are reported of weakening of sediment-like aggregates by addition of hard particles. Sieved mixtures of calcite and halite grains are experimentally compacted in drained pressure cells in the presence of a saturated aqueous solution. The individual halite grains deform easily by pressure solution creep whereas calcite grains act as hard objects and resist compaction. The fastest rate of compaction of the mixed aggregate is not obtained for a 100% halite aggregate but for a content of halite grains between 45% and 75%. We propose that this unusual compaction behavior reflects the competition between two mechanisms at the grain scale: intergranular pressure solution at grain contacts and grain boundary healing between halite grains that prevent further compaction

Structure of plastically compacting granular packings

The developing structure in systems of compacting ductile grains were studied experimentally in two and three dimensions. In both dimensions, the peaks of the radial distribution function were reduced, broadened, and shifted compared with those observed in hard disk- and sphere systems. The geometrical three--grain configurations contributing to the second peak in the radial distribution function showed few but interesting differences between the initial and final stages of the two dimensional compaction. The evolution of the average coordination number as function of packing fraction is compared with other experimental and numerical results from the literature. We conclude that compaction history is important for the evolution of the structure of compacting granular systems.Comment: 12 pages, 12 figure

Role of friction-induced torque in stick-slip motion

We present a minimal quasistatic 1D model describing the kinematics of the transition from static friction to stick-slip motion of a linear elastic block on a rigid plane. We show how the kinematics of both the precursors to frictional sliding and the periodic stick-slip motion are controlled by the amount of friction-induced torque at the interface. Our model provides a general framework to understand and relate a series of recent experimental observations, in particular the nucleation location of micro-slip instabilities and the build up of an asymmetric field of real contact area.Comment: 6 pages, 5 figure

Linear and Nonlinear Rogue Wave Statistics in the Presence of Random Currents

We review recent progress in modeling the probability distribution of wave heights in the deep ocean as a function of a small number of parameters describing the local sea state. Both linear and nonlinear mechanisms of rogue wave formation are considered. First, we show that when the average wave steepness is small and nonlinear wave effects are subleading, the wave height distribution is well explained by a single "freak index" parameter, which describes the strength of (linear) wave scattering by random currents relative to the angular spread of the incoming random sea. When the average steepness is large, the wave height distribution takes a very similar functional form, but the key variables determining the probability distribution are the steepness, and the angular and frequency spread of the incoming waves. Finally, even greater probability of extreme wave formation is predicted when linear and nonlinear effects are acting together.Comment: 25 pages, 12 figure