Diffusive Migration of Low-Mass Proto-planets in Turbulent Disks

Torque fluctuations due to magnetorotational turbulence in proto-planetary disks may greatly influence the migration patterns and survival probabilities of nascent planets. Provided that the turbulence is a stationary stochastic process with finite amplitude and correlation time, the resulting diffusive migration can be described with a Fokker-Planck equation, which we reduce to an advection-diffusion equation. We calibrate the coefficients with existing turbulent-disk simulations and mean-migration estimates, and solve the equation both analytically and numerically. Diffusion tends to dominate over advection for planets of low-mass and those in the outer regions of proto-planetary disks, whether they are described by the Minimum Mass Solar Nebula (MMSN) or by T-Tauri alpha disks. Diffusion systematically reduces the lifetime of most planets, yet it allows a declining fraction of them to survive for extended periods of time at large radii. Mean planet lifetimes can even be formally infinite (e.g. in an infinite steady MMSN), though median lifetimes are always finite. Surviving planets may linger near specific radii where the combined effects of advection and diffusion are minimized, or at large radii, depending on model specifics. The stochastic nature of migration in turbulent disks challenges deterministic planet formation scenarios and suggests instead that a wide variety of planetary outcomes are possible from similar initial conditions. This would contribute to the diversity of (extrasolar) planetary systems.Comment: 31 pages, 7 figures, accepted for publication in Ap

Merlin Phosphorylation by p21-activated Kinase 2 and Effects of Phosphorylation on Merlin Localization

The Nf2 tumor suppressor gene product merlin is related to the membrane-cytoskeleton linker proteins of the band 4.1 superfamily, including ezrin, radixin, and moesin (ERMs). Merlin is regulated by phosphorylation in a Rac/cdc42-dependent fashion. We report that the phosphorylation of merlin at serine 518 is induced by the p21-activated kinase PAK2. This is demonstrated by biochemical fractionation, use of active and dominant-negative mutants of PAK2, and immunodepletion. By using wild-type and mutated forms of merlin and phospho-directed antibodies, we show that phosphorylation of merlin at serine 518 leads to dramatic protein relocalization. Neurofibromatosis type 2 (NF2)1 is an inherited disorder characterized by the development of Schwann cell tumors of the eighth cranial nerve. Mutations and loss of heterozygosity of theNF2 gene have been detected in NF2 patients and in various sporadic tumors, including schwannomas, meningiomas, and ependymomas (1). In further support of a role for NF2 in tumor suppression, mice heterozygous for an Nf2 mutation are predisposed to a wide variety of tumors with high metastatic potential (2). In a separate model in which Nf2 is inactivated specifically in Schwann cells, mice develop schwannomas and Schwann cell hyperplasia (3). The longest and predominant splice form of the Nf2gene codes for a 595-amino acid protein highly similar to the band 4.1 family of proteins. It is most closely related to the ERM proteins,moesin, ezrin, and radixin. The ERM proteins are thought to function as cell membrane-cytoskeleton linkers and are localized to cortical actin structures near the plasma membrane such as microvilli, membrane ruffles, and lamellipodia (4, 5). Likewise, merlin is localized to cortical actin structures, in patterns that partially overlap with the ERMs (1). It has been proposed that intramolecular binding of the N-terminal and C-terminal domains conformationally regulates the ERM proteins by masking binding sites for interacting proteins. The ERMs can also form homodimers and heterodimers, among themselves and with merlin, adding an additional level of complexity to the regulation of these proteins (6). The recently solved crystal structure of the moesin N/C-terminal complex strengthens this model of conformational regulation (7). Given the sequence and, most likely, structural similarities of merlin to the ERM proteins, it is possible that merlin itself could be regulated in a similar fashion. Recent studies (8, 9) have implicated additional factors in the regulation of the ERMs, including phospholipids and phosphorylation. Previous work from our group and others (10, 11) has shown that merlin is differentially phosphorylated as well and that merlin protein levels are affected by growth conditions such as cell confluency, loss of adhesion, or serum deprivation. Merlin is found in an hypophosphorylated form when the combination of cellular and environmental conditions are growth-inhibitory (10). ERMs can be phosphorylated by Rho kinase, and this phosphorylation can affect intramolecular association and cellular localization. Phosphorylation and/or phospholipids may promote the transition of the proteins to an active form by “opening” intra- and intermolecular associations. These active monomers can then bind to other interacting proteins and the actin cytoskeleton and induce actin-rich membrane projections (5,8, 12, 13). The induction of merlin phosphorylation by activated alleles of the Rho family GTPases has also been examined. Interestingly, although activated Rho did not induce noticeable phosphorylation of merlin, activated forms of Rac and cdc42 did. The site of Rac-induced phosphorylation was determined to be a serine at position 518; mutation of serine 518 results in reduced basal phosphorylation and eliminated Rac-induced phosphorylation (11). Although Rac and cdc42 are implicated in the regulation of many pathways, they are most associated with regulation of cytoskeleton reorganization and gene expression (for recent reviews see Refs.14-16). In light of the data demonstrating that activated Rac/cdc42 leads to phosphorylation and possible inactivation of merlin, the elucidation of the responsible effector pathways and their effects on merlin function are of major importance. Understanding this regulation of merlin could lead to a more complete appreciation of the effects of merlin loss in tumors

Cre/lox generation of a novel whole-body Kiss1r KO mouse line recapitulates a hypogonadal, obese, and metabolically-impaired phenotype.

Kisspeptin and its receptor, Kiss1r, act centrally to stimulate reproduction. Recent evidence indicates that kisspeptin is also important for body weight and metabolism, as whole-body Kiss1r KO mice, developed with gene trap technology, display obesity and reduced metabolism. Kiss1r is expressed in brain and multiple peripheral tissues, but it is unknown which is responsible for the metabolic phenotype. Here, we sought to confirm that 1) the metabolic phenotype of the gene trap Kiss1r KOs is due to disruption of kisspeptin signaling and not off-target effects of viral mutagenesis, and 2) the Kiss1r flox line is suitable for creating conditional KOs to study the metabolic phenotype. We used Cre/lox technology (Zp3-Cre/Kiss1r flox) to develop a new global Kiss1r KO ("Kiss1r gKO") to compare with the original gene trap KO phenotype. We confirmed that deleting exon 2 of Kiss1r from the entire body induces hypogonadism in both sexes. Moreover, global deletion of Kiss1r induced obesity in females, but not males, along with increased adiposity and impaired glucose tolerance, similar to the gene trap Kiss1r KOs. Likewise, Kiss1r gKO females had decreased VO2 and VCO2, likely underlying their obesity. These findings support that our previous results in gene trap Kiss1r KOs are due to disrupted kisspeptin signaling, and further highlight a role for Kiss1r signaling in energy expenditure and metabolism besides controlling reproduction. Moreover, given Kiss1r expression in multiple cell-types, our findings indicate that the Kiss1r flox line is viable for future investigations to isolate specific target cells of kisspeptin's metabolic effects

Hospital and Physician Capacity Update

Offers an alternative view of healthcare costs by examining trends in hospital capacity and healthcare labor across regions. Outlines how effective management of healthcare capacity would enable affordable quality care that meets patient needs and wants

The Mason Music & Memory Initiative (M3I)

Educational Objectives 1. Explain the benefits of a nonpharmacological intervention, such as the M3I, for persons with dementia. 2. Describe the work of M3I and its collaboration with students and faculty throughout the state. 3.Highlight lessons learned and future directions for the M3I

Unraveling the acoustic electron-phonon interaction in graphene

Using a first-principles approach we calculate the acoustic electron-phonon couplings in graphene for the transverse (TA) and longitudinal (LA) acoustic phonons. Analytic forms of the coupling matrix elements valid in the long-wavelength limit are found to give an almost quantitative description of the first-principles based matrix elements even at shorter wavelengths. Using the analytic forms of the coupling matrix elements, we study the acoustic phonon-limited carrier mobility for temperatures 0-200 K and high carrier densities of 10^{12}-10^{13} cm^{-2}. We find that the intrinsic effective acoustic deformation potential of graphene is \Xi_eff = 6.8 eV and that the temperature dependence of the mobility \mu ~ T^{-\alpha} increases beyond an \alpha = 4 dependence even in the absence of screening when the full coupling matrix elements are considered. The large disagreement between our calculated deformation potential and those extracted from experimental measurements (18-29 eV) indicates that additional or modified acoustic phonon-scattering mechanisms are at play in experimental situations.Comment: 7 pages, 3 figure