Circumventing embryonic lethality with Lcmt1 deficiency: generation of hypomorphic Lcmt1 mice with reduced protein phosphatase 2A methyltransferase expression and defects in insulin signaling.

Protein phosphatase 2A (PP2A), the major serine/threonine phosphatase in eukaryotic cells, is a heterotrimeric protein composed of structural, catalytic, and targeting subunits. PP2A assembly is governed by a variety of mechanisms, one of which is carboxyl-terminal methylation of the catalytic subunit by the leucine carboxyl methyltransferase LCMT1. PP2A is nearly stoichiometrically methylated in the cytosol, and although some PP2A targeting subunits bind independently of methylation, this modification is required for the binding of others. To examine the role of this methylation reaction in mammalian tissues, we generated a mouse harboring a gene-trap cassette within intron 1 of Lcmt1. Due to splicing around the insertion, Lcmt1 transcript and LCMT1 protein levels were reduced but not eliminated. LCMT1 activity and methylation of PP2A were reduced in a coordinate fashion, suggesting that LCMT1 is the only PP2A methyltransferase. These mice exhibited an insulin-resistance phenotype, indicating a role for this methyltransferase in signaling in insulin-sensitive tissues. Tissues from these animals will be vital for the in vivo identification of methylation-sensitive substrates of PP2A and how they respond to differing physiological conditions

Energy Gaps in Graphene Nanoribbons

Based on a first-principles approach, we present scaling rules for the band gaps of graphene nanoribbons (GNRs) as a function of their widths. The GNRs considered have either armchair or zigzag shaped edges on both sides with hydrogen passivation. Both varieties of ribbons are shown to have band gaps. This differs from the results of simple tight-binding calculations or solutions of the Dirac's equation based on them. Our {\it ab initio} calculations show that the origin of energy gaps for GNRs with armchair shaped edges arises from both quantum confinement and the crucial effect of the edges. For GNRs with zigzag shaped edges, gaps appear because of a staggered sublattice potential on the hexagonal lattice due to edge magnetization. The rich gap structure for ribbons with armchair shaped edges is further obtained analytically including edge effects. These results reproduce our {\it ab initio} calculation results very well

Electron Beam Supercollimation in Graphene Superlattices

Although electrons and photons are intrinsically different, importing useful concepts in optics to electronics performing similar functions has been actively pursued over the last two decades. In particular, collimation of an electron beam is a long-standing goal. We show that ballistic propagation of an electron beam with virtual no spatial spreading or diffraction, without a waveguide or external magnetic field, can be achieved in graphene under an appropriate class of experimentally feasible one-dimensional external periodic potentials. The novel chiral quasi-one-dimensional metallic state that the charge carriers are in originates from a collapse of the intrinsic helical nature of the charge carriers in graphene owing to the superlattice potential. Beyond providing a new way to constructing chiral one-dimensional states in two dimensions, our findings should be useful in graphene-based electronic devices (e.g., for information processing) utilizing some of the highly developed concepts in optics.Comment: 7 pages, 4 figures (including supporting online material), published online in Nano Letter

New Generation of Massless Dirac Fermions in Graphene under External Periodic Potentials

We show that new massless Dirac fermions are generated when a slowly varying periodic potential is applied to graphene. These quasiparticles, generated near the supercell Brillouin zone boundaries with anisotropic group velocity, are different from the original massless Dirac fermions. The quasiparticle wavevector (measured from the new Dirac point), the generalized pseudospin vector, and the group velocity are not collinear. We further show that with an appropriate periodic potential of triangular symmetry, there exists an energy window over which the only available states are these quasiparticles, thus, providing a good system to probe experimentally the new massless Dirac fermions. The required parameters of external potentials are within the realm of laboratory conditions.Comment: 4 pages, 4 figure

Regression Analysis of a Disease Onset Distribution Using Diagnosis Data

We consider methods for estimating the effect of a covariate on a disease onset distribution when the observed data structure consists of right-censored data on diagnosis times and current status data on onset times amongst individuals who have not yet been diagnosed. Dunson and Baird (2001) approached this problem using maximum likelihood, under the assumption that the ratio of the diagnosis and onset distributions is monotonic non-decreasing. As an alternative, we propose a two-step estimator, an extension of the approach of van der Laan, Jewell and Petersen (1997) in the single sample setting, that is computationally much simpler and requires no assumptions on this ratio. A simulation study is performed comparing estimates obtained from these two approaches, as well as that from a standard current status analysis that ignores diagnosis data. Results indicate that the Dunson and Baird estimator outperforms the two-step estimator when the monotonicity assumption holds, but the reverse is true when the assumption fails. The simple current status estimator loses only a small amount of precision in comparison to the two-step procedure but requires monitoring time information for all individuals. In the data that motivated this work, a study of uterine fibroids and chemical exposure to dioxin, the monotonicity assumption is seen to fail. Here, the two-step and current status estimators both show no significant association between the level of dioxin exposure and the hazard for onset of uterine fibroids; the two-step estimator of the relative hazard associated with increasing levels of exposure has the least estimated variance amongst the three estimators considered

Stimulus Threat and Exposure Context Modulate the Effect of Mere Exposure on Approach Behaviors

Mere-exposure (ME) research has found that initially neutral objects made familiar are preferred relative to novel objects. Recent work extends these preference judgments into the behavioral domain by illustrating that mere exposure prompts approachoriented behavior toward familiar stimuli. However, no investigations have examined the effect of mere exposure on approach-oriented behavior toward threatening stimuli. The current work examines this issue and also explores how exposure context interacts with stimulus threat to influence behavioral tendencies. In two experiments participants were presented with both mere-exposed and novel stimuli and approach speed was assessed. In the first experiment, when stimulus threat was presented in a homogeneous format (i.e., participants viewed exclusively neutral or threatening stimuli), ME potentiated approach behaviors for both neutral and threatening stimuli. However, in the second experiment, in which stimulus threat was presented in a heterogeneous fashion (i.e., participants viewed both neutral and threatening stimuli), mere exposure facilitated approach only for initially neutral stimuli. These results suggest that ME effects on approach behaviors are highly context sensitive and depend on both stimulus valence and exposure context. Further implications of these findings for the ME literature are discussed

Variation in Ringed Seal Density and Abundance in Western Hudson Bay Estimated from Aerial Surveys, 1995 to 2013

We conducted systematic aerial surveys of ringed seals along strip transects in western Hudson Bay (WHB), Canada, in late May to early June of 1995–97, 1999, 2000, 2007–10, and 2013. The density of ringed seals hauled out on ice over the entire study area ranged from 1.22 seals/km2 in 1995, to 0.20 seals/km2 in 2013. Density estimates varied significantly over the study period and, with the exception of 2013, appeared to follow a cyclical pattern. Although density estimates also appear to follow a downward trend over time, results of multiple linear regression, weighted by survey effort, indicated no significant trend in ringed seal density as a function of year, survey date, or proportion of open water. In addition, no significant correlation was observed among any of the environmental variables and density estimates. As the proportion of seals hauled out at the time of the survey is unknown, the density estimates of WHB ringed seals presented in this study should be considered indices that might be useful to explore trends in abundance. Although our results do not indicate that a significant decline has occurred, the low density estimate in 2013 may indicate that population changes unrelated to a natural cycle are taking place. We were unable to test for direct effects of changes in food supply or predation, but polar bears, Arctic foxes, and Inuit communities in the Hudson Bay region all would be negatively affected should ringed seal populations undergo significant declines. Further monitoring and directed research are necessary to understand what mechanism may be responsible for the observed changes in ringed seal density.Nous avons fait les levés aériens systématiques de phoques annelés sur de longs transects en bandes dans l’ouest de la baie d’Hudson (OBH), au Canada, de la fin de mai au début de juin des années 1995 à 1997, 1999, 2000, 2007 à 2010 et 2013. Pendant toute la durée de l’étude, la densité de phoques annelés hissés sur la glace a varié de 1,22 phoque/km2 en 1995 à 0,20 phoque/km2 en 2013. Les estimations de densité ont varié considérablement au cours de la période visée par l’étude et, à l’exception de 2013, elles semblaient suivre un profil cyclique. Bien que les estimations de densité semblent également suivre une tendance à la baisse au fil du temps, les résultats de la régression linéaire multiple, pondérée par les levés, n’ont indiqué aucune tendance importante sur le plan de la densité de phoques annelés en fonction de l’année, de la date des levés ou de la proportion d’eaux libres. Par ailleurs, aucune corrélation importante n’a été observée pour n’importe quelle variable environnementale et n’importe quelle estimation de densité. Puisque la proportion de phoques hissés au moment des levés est inconnue, les estimations de densité de phoques annelés dans l’OBH présentées dans cette étude devraient être considérées comme des indices susceptibles d’aider à explorer les tendances en matière d’abondance. Bien que nos résultats ne laissent pas entrevoir la présence d’un déclin important, la faible estimation de densité enregistrée en 2013 pourrait indiquer qu’il se produit des changements de population et que ceux-ci ne sont pas attribuables à un cycle naturel. Nous n’avons pu examiner les effets directs des changements en matière d’approvisionnement alimentaire ou de prédation, mais les ours polaires, les renards arctiques et les communautés inuites de la région de la baie d’Hudson subiraient tous des effets négatifs si les populations de phoques annelés diminuaient considérablement. Il y a lieu de faire de la surveillance et des recherches dirigées pour comprendre à quel mécanisme les changements observés sur le plan de la densité de phoques annelés pourrait être attribuable