CARMIL family proteins as multidomain regulators of actin-based motility

CARMILs are large multidomain proteins that regulate the actin-binding activity of capping protein (CP), a major capper of actin filament barbed ends in cells. CARMILs bind directly to CP and induce a conformational change that allosterically decreases but does not abolish its actin-capping activity. The CP-binding domain of CARMIL consists of the CP-interaction (CPI) and CARMIL-specific interaction (CSI) motifs, which are arranged in tandem. Many cellular functions of CARMILs require the interaction with CP; however, a more surprising result is that the cellular function of CP in cells appears to require binding to a CARMIL or another protein with a CPI motif, suggesting that CPI-motif proteins target CP and modulate its actin-capping activity. Vertebrates have three highly conserved genes and expressed isoforms of CARMIL with distinct and overlapping localizations and functions in cells. Various domains of these CARMIL isoforms interact with plasma membranes, vimentin intermediate filaments, SH3-containing class I myosins, the dual-GEF Trio, and other adaptors and signaling molecules. These biochemical properties suggest that CARMILs play a variety of membrane-associated functions related to actin assembly and signaling. CARMIL mutations and variants have been implicated in several human diseases. We focus on roles for CARMILs in signaling in addition to their function as regulators of CP and actin. </jats:p

Actin Dynamics: Tropomyosin Provides Stability

AbstractTropomyosin stabilizes actin filaments, while ADF/cofilin promotes their disassembly. These two proteins compete with each other for binding to the actin filament, providing a critical balance for actin assembly in vivo

Multidisciplinary analysis of actively controlled large flexible spacecraft

The control of Flexible Structures (COFS) program has supported the development of an analysis capability at the Langley Research Center called the Integrated Multidisciplinary Analysis Tool (IMAT) which provides an efficient data storage and transfer capability among commercial computer codes to aid in the dynamic analysis of actively controlled structures. IMAT is a system of computer programs which transfers Computer-Aided-Design (CAD) configurations, structural finite element models, material property and stress information, structural and rigid-body dynamic model information, and linear system matrices for control law formulation among various commercial applications programs through a common database. Although general in its formulation, IMAT was developed specifically to aid in the evaluation of the structures. A description of the IMAT system and results of an application of the system are given

Septins regulate junctional integrity of endothelial monolayers

Junctional integrity of endothelial monolayers is crucial to control movement of molecules and cells across the endothelium. Examining the structure and dynamics of cell junctions in endothelial monolayers, we discovered a role for septins. Contacts between adjacent endothelial cells were dynamic, with protrusions extending above or below neighboring cells. Vascular endothelial cadherin (VE-cadherin) was present at cell junctions, with a membrane-associated layer of F-actin. Septins localized at cell-junction membranes, in patterns distinct from VE-cadherin and F-actin. Septins assumed curved and scallop-shaped patterns at junctions, especially in regions of positive membrane curvature associated with actin-rich membrane protrusions. Depletion of septins led to disrupted morphology of VE-cadherin junctions and increased expression of VE-cadherin. In videos, septin-depleted cells displayed remodeling at cell junctions; regions with VE-cadherin were broader, and areas with membrane ruffling were wider. Septin depletion and junction disruption led to functional loss of junctional integrity, revealed by decreased transendothelial electric resistance and increased transmigration of immune cells. We conclude that septins, as cytoskeletal elements associated with the plasma membrane, are important for cell junctions and junctional integrity of endothelial monolayers, functioning at regions of positive curvature in support of actin-rich protrusions to promote cadherin-based cell junctions.</jats:p

Modeling the Formation of Clouds in Brown Dwarf Atmospheres

Because the opacity of clouds in substellar mass object (SMO) atmospheres depends on the composition and distribution of particle sizes within the cloud, a credible cloud model is essential for accurately modeling SMO spectra and colors. We present a one--dimensional model of cloud particle formation and subsequent growth based on a consideration of basic cloud microphysics. We apply this microphysical cloud model to a set of synthetic brown dwarf atmospheres spanning a broad range of surface gravities and effective temperatures (g_surf = 1.78 * 10^3 -- 3 * 10^5 cm/s^2 and T_eff = 600 -- 1600 K) to obtain plausible particle sizes for several abundant species (Fe, Mg2SiO4, and Ca2Al2SiO7). At the base of the clouds, where the particles are largest, the particle sizes thus computed range from ~5 microns to over 300 microns in radius over the full range of atmospheric conditions considered. We show that average particle sizes decrease significantly with increasing brown dwarf surface gravity. We also find that brown dwarfs with higher effective temperatures have characteristically larger cloud particles than those with lower effective temperatures. We therefore conclude that it is unrealistic when modeling SMO spectra to apply a single particle size distribution to the entire class of objects.Comment: 25 pages; 8 figures. We have added considerable detail describing the physics of the cloud model. We have also added discussions of the issues of rainout and the self-consistent coupling of clouds with brown dwarf atmospheric models. We have updated figures 1, 3, and 4 with new vertical axis labels and new particle sizes for forsterite and gehlenite. Accepted to the Astrophysical Journal, Dec. 2, 200

Checkpoint control of mitotic exit—do budding yeast mind the GAP?

Cell cycle checkpoints can delay mitotic exit in budding yeast. The master controller is the small GTPase Tem1, with inputs from a proposed guanine nucleotide exchange factor (GEF), Lte1, and a GTPase-activating protein (GAP), Bub2/Bfa1. In this issue, Fraschini et al. (p. 335) show that GAP activity of Bub2/Bfa1 appears to be dispensable for inactivation of Tem1 in cells. Their results call into question the GTP/GDP switch model for Tem1 activity, as have other results in the past. The paper also focuses attention on the two spindle pole bodies as potential sites for regulation of Tem1

Chaos in Time Dependent Variational Approximations to Quantum Dynamics

Dynamical chaos has recently been shown to exist in the Gaussian approximation in quantum mechanics and in the self-consistent mean field approach to studying the dynamics of quantum fields. In this study, we first show that any variational approximation to the dynamics of a quantum system based on the Dirac action principle leads to a classical Hamiltonian dynamics for the variational parameters. Since this Hamiltonian is generically nonlinear and nonintegrable, the dynamics thus generated can be chaotic, in distinction to the exact quantum evolution. We then restrict attention to a system of two biquadratically coupled quantum oscillators and study two variational schemes, the leading order large N (four canonical variables) and Hartree (six canonical variables) approximations. The chaos seen in the approximate dynamics is an artifact of the approximations: this is demonstrated by the fact that its onset occurs on the same characteristic time scale as the breakdown of the approximations when compared to numerical solutions of the time-dependent Schrodinger equation.Comment: 10 pages (12 figures), RevTeX (plus macro), uses epsf, minor typos correcte

The Incidence of Low-Metallicity Lyman-Limit Systems at z~3.5: Implications for the Cold-Flow Hypothesis of Baryonic Accretion

Cold accretion is a primary growth mechanism of simulated galaxies, yet observational evidence of "cold flows" at redshifts where they should be most efficient ($z=2$-4) is scarce. In simulations, cold streams manifest as Lyman-limit absorption systems (LLSs) with low heavy-element abundances similar to those of the diffuse IGM. Here we report on an abundance survey of 17 H I-selected LLSs at $z=3.2$-4.4 which exhibit no metal absorption in SDSS spectra. Using medium-resolution spectra obtained at Magellan, we derive ionization-corrected metallicities (or limits) with a Markov-Chain Monte Carlo sampling that accounts for the large uncertainty in $N_{\rm HI}$ measurements typical of LLSs. The metal-poor LLS sample overlaps with the IGM in metallicity and is best described by a model where $71^{+13}_{-11}\%$ are drawn from the IGM chemical abundance distribution. These represent roughly half of all LLSs at these redshifts, suggesting that 28-40$\%$ of the general LLS population at $z\sim3.7$ could trace unprocessed gas. An ancillary sample of ten LLSs without any a priori metal-line selection is best fit with $48^{+14}_{-12}\%$ of metallicities drawn from the IGM. We compare these results with regions of a moving-mesh simulation; the simulation finds only half as many baryons in IGM-metallicity LLSs, and most of these lie beyond the virial radius of the nearest galaxy halo. A statistically significant fraction of all LLSs have low metallicity and therefore represent candidates for accreting gas; large-volume simulations can establish what fraction of these candidates actually lie near galaxies and the observational prospects for detecting the presumed hosts in emission.Comment: 19 pages, 17 figures; Submitted to ApJ; Corrected figure 16

Ginzburg-Landau theory for the conical cycloid state in multiferroics: applications to CoCr2_2O4_4

We show that the cycloidal magnetic order of a multiferroic can arise in the absence of spin and lattice anisotropies, for e.g., in a cubic material, and this explains the occurrence of such a state in CoCr$_2$O$_4$. We discuss the case when this order coexists with ferromagnetism in a so called `conical cycloid' state, and show that a direct transition to this state from the ferromagnet is necessarily first order. On quite general grounds, the reversal of the direction of the uniform magnetization in this state can lead to the reversal of the electric polarization as well, without the need to invoke `toroidal moment' as the order parameter.Comment: 6 pages, 3 figures, accepted for publication in Phys. Rev.