One-Armed Spiral Waves in Galaxy Simulations with Counter-Rotating Stars

Motivated by observations of disk galaxies with counter-rotating stars, we have run two-dimensional, collisionless N-body simulations of disk galaxies with significant counter-rotating components. For all our simulations the initial value of Toomre's stability parameter was Q = 1.1. The percentage of counter-rotating particles ranges from 25% to 50%. A stationary one-arm spiral wave is observed to form in each run, persisting from a few to five rotation periods, measured at the half-mass radius. In one run, the spiral wave was initially a leading arm which subsequently transformed into a trailing arm. We also observed a change in spiral direction in the run initially containing equal numbers of particles orbiting in both directions. The results of our simulations support an interpretation of the one armed waves as due to the two stream instability.Comment: 13 pages, 4 figure

Negative Energy and Angular Momentum Modes of Thin Accretion Disks

This work derives the linearized equations of motion, the Lagrangian density, the Hamiltonian density, and the canonical angular momentum density for general perturbations [$\propto \exp(im\phi)$ with $m=0,\pm 1,..$] of a geometrically thin self-gravitating, homentropic fluid disk including the pressure. The theory is applied to ``eccentric,'' $m=\pm 1$ perturbations of a geometrically thin Keplerian disk. We find $m=1$ modes at low frequencies relative to the Keplerian frequency. Further, it shown that these modes can have negative energy and negative angular momentum. The radial propagation of these low frequency $m=1$ modes can transport angular momentum away from the inner region of a disk and thus increase the rate of mass accretion. Depending on the radial boundary conditions there can be discrete low-frequency, negative-energy, $m=1$ modes.Comment: 24 pages, 8 figure

NM23 proteins: innocent bystanders or local energy boosters for CFTR?

NM23 proteins NDPK-A and -B bind to the cystic fibrosis (CF) protein CFTR in different ways from kinases such as PKA, CK2 and AMPK or linkers to cell calcium such as calmodulin and annexins. NDPK-A (not -B) interacts with CFTR through reciprocal AMPK binding/control, whereas NDPK-B (not -A) binds directly to CFTR. NDPK-B can activate G proteins without ligand-receptor coupling, so perhaps NDPK-B's binding influences energy supply local to a nucleotide-binding site (NBD1) needed for CFTR to function. Curiously, CFTR (ABC-C7) is a member of the ATP-binding cassette (ABC) protein family that does not obey 'clan rules'; CFTR channels anions and is not a pump, regulates disparate processes, is itself regulated by multiple means and is so pleiotropic that it acts as a hub that orchestrates calcium signaling through its consorts such as calmodulin/annexins. Furthermore, its multiple partners make CFTR dance to different tunes in different cellular and subcellular locations as it recycles from the plasma membrane to endosomes. CFTR function in airway apical membranes is inhibited by smoking which has been dubbed 'acquired CF'. CFTR alone among family members possesses a trap for other proteins that it unfurls as a 'fish-net' and which bears consensus phosphorylation sites for many protein kinases, with PKA being the most canonical. Recently, the site of CFTR's commonest mutation has been proposed as a knock-in mutant that alters allosteric control of kinase CK2 by log orders of activity towards calmodulin and other substrates after CFTR fragmentation. This link from CK2 to calmodulin that binds the R region invokes molecular paths that control lumen formation, which is incomplete in the tracheas of some CF-affected babies. Thus, we are poised to understand the many roles of NDPK-A and -B in CFTR function and, especially lumen formation, which is defective in the gut and lungs of many CF babies

Revertant mutants modify, but do not rescue, the gating defect of the cystic fibrosis mutant G551D-CFTR

Cystic fibrosis (CF) is caused by dysfunction of the epithelial anion channel cystic fibrosis transmembrane conductance regulator (CFTR). One strategy to restore function to CF mutants is to suppress defects in CFTR processing and function using revertant mutations. Here, we investigate the effects of the revertant mutations G550E and 4RK (the simultaneous disruption of four arginine-framed tripeptides (AFTs): R29K, R516K, R555K and R766K) on the CF mutant G551D, which impairs severely channel gating without altering protein processing and which affects a residue in the same α-helix as G550 and R555. Both G550E and 4RK augmented strongly CFTR-mediated iodide efflux from BHK cells expressing G551D-CFTR. To learn how revertant mutations influence G551D-CFTR function, we studied protein processing and single-channel behaviour. Neither G550E nor 4RK altered the expression and maturation of G551D-CFTR protein. By contrast, both revertants had marked effects on G551D-CFTR channel gating, increasing strongly opening frequency, while 4RK also diminished noticeably the duration of channel openings. Because G551D-CFTR channel gating is ATP independent, we investigated whether revertant mutations restore ATP dependence to G551D-CFTR. Like wild-type CFTR, the activity of 4RK-G551D-CFTR varied with ATP concentration, suggesting that 4RK confers some ATP dependence on the G551D-CFTR channel. Thus, the revertant mutations G550E and 4RK alter the gating pattern and ATP dependence of G551D-CFTR without restoring single-channel activity to wild-type levels. Based on their impact on the CF mutants F508del and G551D, we conclude that G550E and 4RK have direct effects on CFTR structure, but that their action on CFTR processing and channel function is CF mutation specific

Application of high-resolution single-channel recording to functional studies of cystic fibrosis mutants

The patch-clamp technique is a powerful and versatile method to investigate the cystic fibrosis transmem-brane conductance regulator (CFTR) Cl(−) channel, its malfunction in disease and modulation by small molecules. Here, we discuss how the molecular behaviour of CFTR is investigated using high-resolution single-channel recording and kinetic analyses of channel gating. We review methods used to quantify how cystic fibrosis (CF) mutants perturb the biophysical properties and regulation of CFTR. By explaining the relationship between macroscopic and single-channel currents, we demonstrate how single-channel data provide molecular explanations for changes in CFTR-mediated transepithelial ion transport elicited by CF mutants