Expanding the View of IKK: New Substrates and New Biology

The inhibitor of kappa B kinase (IKK) family consists of IKKα, IKKβ, and the IKK-related kinases TBK1 and IKKε. These kinases are considered master regulators of inflammation and innate immunity via their control of the transcription factors NF-κB, IRF3, and IRF7. Novel phosphorylated substrates have been attributed to these kinases, a subset of which is not directly related to either inflammation or innate immunity. These findings have greatly expanded the perspectives on the biological activities of these kinases. In this review we highlight some of the novel substrates for this kinase family and discuss the biological implications of these phosphorylation events

TBK1 Limits mTORC1 by Promoting Phosphorylation of Raptor Ser877

While best known for its role in the innate immune system, the TANK-binding kinase 1 (TBK1) is now known to play a role in modulating cellular growth and autophagy. One of the major ways that TBK1 accomplishes this task is by modulating the mechanistic Target of Rapamycin (mTOR), a master regulator that when activated promotes cell growth and inhibits autophagy. However, whether TBK1 promotes or inhibits mTOR activity is highly cell type and context dependent. To further understand the mechanism whereby TBK1 regulates mTOR, we tested the hypothesis that TBK1 phosphorylates a key component of the mTOR complex 1 (mTORC1), Raptor. Using kinase assays coupled with mass spectrometry, we mapped the position of the TBK1 dependent phosphorylation sites on Raptor in vitro. Among the sites identified in vitro, we found that TBK1 promotes Raptor Ser877 phosphorylation in cells both basally and in response to pathogen-associated molecules known to induce TBK1 activity. The levels of Raptor Ser877 phosphorylation were inversely correlated with the levels of mTOR activity. Expression of a mutant Raptor that could not be phosphorylated at Ser877 led to an increase in mTORC1 activity. We conclude that TBK1 limits mTORC1 activity by promoting Raptor Ser877 phosphorylation

Elemental and Isotopic Analysis of Uranium Oxide an NIST Glass Standards by FEMTOSECOND-LA-ICP-MIC-MS

The objective of this work was to test and demonstrate the analytical figures of merit of a femtosecond-laser ablation (fs-LA) system coupled with an inductively coupled plasma-multi-ion collector-mass spectrometer (ICP-MIC-MS). The mobile fs-LA sampling system was designed and assembled at Ames Laboratory and shipped to Oak Ridge National Laboratory (ORNL), where it was integrated with an ICP-MIC-MS. The test period of the integrated systems was February 2-6, 2009. Spatially-resolved analysis of particulate samples is accomplished by 100-shot laser ablation using a fs-pulsewidth laser and monitoring selected isotopes in the resulting ICP-MS transient signal. The capability of performing high sensitivity, spatially resolved, isotopic analyses with high accuracy and precision and with virtually no sample preparation makes fs-LA-ICP-MIC-MS valuable for the measurement of actinide isotopes at low concentrations in very small samples for nonproliferation purposes. Femtosecond-LA has been shown to generate particles from the sample that are more representative of the bulk composition, thereby minimizing weaknesses encountered in previous work using nanosecond-LA (ns-LA). The improvement of fs- over ns-LA sampling arises from the different mechanisms for transfer of energy into the sample in these two laser pulse-length regimes. The shorter duration fs-LA pulses induce less heating and cause less damage to the sample than the longer ns pulses. This results in better stoichiometric sampling (i.e., a closer correlation between the composition of the ablated particles and that of the original solid sample), which improves accuracy for both intra- and inter-elemental analysis. The primary samples analyzed in this work are (a) solid uranium oxide powdered samples having different {sup 235}U to {sup 238}U concentration ratios, and (b) glass reference materials (NIST 610, 612, 614, and 616). Solid uranium oxide samples containing {sup 235}U in depleted, natural, and enriched abundances were analyzed as particle aggregates immobilized in a collodion substrate. The uranium oxide samples were nuclear reference materials (CRMs U0002, U005-A, 129-A, U015, U030-A, and U050) obtained from New Brunswick Laboratory-USDOE

Reflection and Ducting of Gravity Waves Inside the Sun

Internal gravity waves excited by overshoot at the bottom of the convection zone can be influenced by rotation and by the strong toroidal magnetic field that is likely to be present in the solar tachocline. Using a simple Cartesian model, we show how waves with a vertical component of propagation can be reflected when traveling through a layer containing a horizontal magnetic field with a strength that varies with depth. This interaction can prevent a portion of the downward-traveling wave energy flux from reaching the deep solar interior. If a highly reflecting magnetized layer is located some distance below the convection zone base, a duct or wave guide can be set up, wherein vertical propagation is restricted by successive reflections at the upper and lower boundaries. The presence of both upward- and downward-traveling disturbances inside the duct leads to the existence of a set of horizontally propagating modes that have significantly enhanced amplitudes. We point out that the helical structure of these waves makes them capable of generating an alpha-effect, and briefly consider the possibility that propagation in a shear of sufficient strength could lead to instability, the result of wave growth due to over-reflection.Comment: 23 pages, 5 figures. Accepted for publication in Solar Physic

Physical model for the gating mechanism of ionic channels

We propose a physical model for the gating mechanism of ionic channels. First, we investigate the fluctuation-mediated interactions between two proteins imbedded in a cellular membrane and find that the interaction depends on their orientational configuration as well as the distance between them. The orientational dependence of interactions arises from the fact that the noncircular cross-sectional shapes of individual proteins constrain fluctuations of the membrane differently according to their orientational configuration. Then, we apply these interactions to ionic channels composed of four, five, and six proteins. As the gating stimulus creates the changes in the structural shape of proteins composing ionic channels, the orientational configuration of the ionic channels changes due to the free energy minimization, and ionic channels are open or closed according to the conformation thereof.open3

'Education, education, education' : legal, moral and clinical

This article brings together Professor Donald Nicolson's intellectual interest in professional legal ethics and his long-standing involvement with law clinics both as an advisor at the University of Cape Town and Director of the University of Bristol Law Clinic and the University of Strathclyde Law Clinic. In this article he looks at how legal education may help start this process of character development, arguing that the best means is through student involvement in voluntary law clinics. And here he builds upon his recent article which argues for voluntary, community service oriented law clinics over those which emphasise the education of students

The Influence of Racial Identity Profiles on the Relationship Between Racial Discrimination and Depressive Symptoms

This study examined the association between racial identity profiles, discrimination, and mental health outcomes. African American college students (N = 194) completed measures of racial discrimination, racial identity, college hassles, and depressive symptoms. Four meaningful profiles emerged through a cluster analysis of seven dimensions of racial identity assessed using the Multidimensional Inventory of Black Identity (MIBI). Results suggested racial identity moderates the relation between discrimination and depressive symptoms. Students whose racial identity profile involves the goal of blending with the mainstream and focusing on shared human qualities rather than race as a core ideological concept had a significantly stronger association between racial discrimination and depressive symptoms. The results hold implications for investigating the experience of racial discrimination and conceptualization of racial identity

Fitting the integrated Spectral Energy Distributions of Galaxies

Fitting the spectral energy distributions (SEDs) of galaxies is an almost universally used technique that has matured significantly in the last decade. Model predictions and fitting procedures have improved significantly over this time, attempting to keep up with the vastly increased volume and quality of available data. We review here the field of SED fitting, describing the modelling of ultraviolet to infrared galaxy SEDs, the creation of multiwavelength data sets, and the methods used to fit model SEDs to observed galaxy data sets. We touch upon the achievements and challenges in the major ingredients of SED fitting, with a special emphasis on describing the interplay between the quality of the available data, the quality of the available models, and the best fitting technique to use in order to obtain a realistic measurement as well as realistic uncertainties. We conclude that SED fitting can be used effectively to derive a range of physical properties of galaxies, such as redshift, stellar masses, star formation rates, dust masses, and metallicities, with care taken not to over-interpret the available data. Yet there still exist many issues such as estimating the age of the oldest stars in a galaxy, finer details ofdust properties and dust-star geometry, and the influences of poorly understood, luminous stellar types and phases. The challenge for the coming years will be to improve both the models and the observational data sets to resolve these uncertainties. The present review will be made available on an interactive, moderated web page (sedfitting.org), where the community can access and change the text. The intention is to expand the text and keep it up to date over the coming years.Comment: 54 pages, 26 figures, Accepted for publication in Astrophysics & Space Scienc