Mcl-1 integrates the opposing actions of signaling pathways that mediate survival and apoptosis

Mcl-1 is a member of the Bcl2-related protein family that is a critical mediator of cell survival. Exposure of cells to stress causes inhibition of Mcl-1 mRNA translation and rapid destruction of Mcl-1 protein by proteasomal degradation mediated by a phosphodegron created by glycogen synthase kinase 3 (GSK3) phosphorylation of Mcl-1. Here we demonstrate that prior phosphorylation of Mcl-1 by the c-Jun N-terminal protein kinase (JNK) is essential for Mcl-1 phosphorylation by GSK3. Stress-induced Mcl-1 degradation therefore requires the coordinated activity of JNK and GSK3. Together, these data establish that Mcl-1 functions as a site of signal integration between the proapoptotic activity of JNK and the prosurvival activity of the AKT pathway that inhibits GSK3

Data reduction methods for single-mode optical interferometry - Application to the VLTI two-telescopes beam combiner VINCI

The interferometric data processing methods that we describe in this paper use a number of innovative techniques. In particular, the implementation of the wavelet transform allows us to obtain a good immunity of the fringe processing to false detections and large amplitude perturbations by the atmospheric piston effect, through a careful, automated selection of the interferograms. To demonstrate the data reduction procedure, we describe the processing and calibration of a sample of stellar data from the VINCI beam combiner. Starting from the raw data, we derive the angular diameter of the dwarf star Alpha Cen A. Although these methods have been developed specifically for VINCI, they are easily applicable to other single-mode beam combiners, and to spectrally dispersed fringes.Comment: Accepted for publication in Astronomy & Astrophysics, 17 pages, 19 figure

A Protein Scaffold Coordinates SRC-Mediated JNK Activation in Response to Metabolic Stress

Obesity is a major risk factor for the development of metabolic syndrome and type 2 diabetes. How obesity contributes to metabolic syndrome is unclear. Free fatty acid (FFA) activation of a non-receptor tyrosine kinase (SRC)-dependent cJun NH2-terminal kinase (JNK) signaling pathway is implicated in this process. However, the mechanism that mediates SRC-dependent JNK activation is unclear. Here, we identify a role for the scaffold protein JIP1 in SRC-dependent JNK activation. SRC phosphorylation of JIP1 creates phosphotyrosine interaction motifs that bind the SH2 domains of SRC and the guanine nucleotide exchange factor VAV. These interactions are required for SRC-induced activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module. The JIP1 scaffold protein, therefore, plays a dual role in FFA signaling by coordinating upstream SRC functions together with downstream effector signaling by the JNK pathway

Discrete approximations for complex Kac-Moody groups

We construct a map from the classifying space of a discrete Kac-Moody group over the algebraic closure of the field with p elements to the classifying space of a complex topological Kac-Moody group and prove that it is a homology equivalence at primes q different from p. This generalises a classical result of Quillen-Friedlander-Mislin for Lie groups. As an application, we construct unstable Adams operations for general Kac-Moody groups compatible with the Frobenius homomorphism. In contrast to the Lie case, the homotopy fixed points of these unstable Adams operations cannot be realized at q as the classifying spaces of Kac-Moody groups over finite fields. Our results rely on new integral homology decompositions for certain infinite dimensional unipotent subgroups of discrete Kac-Moody groups.Comment: New title and revised introduction, references added; results and proofs unchanged, 31 pages, 1 figur

On the effect of different flux limiters on the performance of an engine gas exchange gas-dynamic model

[EN] A suitable tool for the design of intake and exhaust systems of internal combustion engines is provided by time domain non-linear finite volume models. These models, however, are affected by overshoots at discontinuities and numerical dispersion unless some flux limiter is used. In this paper, the effect of the most relevant of such flux limiters on a non-linear staggered-mesh finite-volume model is evaluated. Flux-Corrected-Transport (FCT) and Total Variation Diminishing (TVD) schemes, together with a Momentum Diffusion Term (MDT) are presented for such a model, and the performance of the resulting methods is checked in different problems representative of the influence of engine gas exchange flows on engine performance and intake and exhaust noise. First, two one-dimensional cases are considered: the shock-tube problem, and the propagation of a finite amplitude pressure pulse. Secondly, a simple but representative three-dimensional geometry is studied. From the results obtained, it can be concluded that, even if none of the methods is able to handle properly the three problems considered, the FCT method provides the best overall performance. (C) 2017 Elsevier Ltd. All rights reserved.M. Hernandez is partially supported through contract FPI-S2-2015-1064 of Programa de Apoyo para la Investigacion y Desarrollo (PAID) of Universitat Politecnica de Valencia.Torregrosa, AJ.; Broatch, A.; Arnau Martínez, FJ.; Hernández-Marco, M. (2017). On the effect of different flux limiters on the performance of an engine gas exchange gas-dynamic model. International Journal of Mechanical Sciences. 133:740-751. https://doi.org/10.1016/j.ijmecsci.2017.09.029S74075113

The interferometric diameter and internal structure of Sirius A

The interferometric observations of dwarf stars in the solar neighbourhood, combined with Hipparcos parallaxes provide very precise values of their linear diameters. In this paper, we report the direct measurement of the angular diameter of the bright star Sirius A with the VINCI/VLTI instrument. We obtain a uniform disk angular diameter of UD = 5.936 +/- 0.016 mas in the K band and a limb darkened value of LD = 6.039 +/- 0.019 mas. In combination with the Hipparcos parallax of 379.22 +/- 1.58 mas, this translates into a linear diameter of 1.711 +/- 0.013 Dsun. Using the VINCI/VLTI interferometric diameter and the published properties of Sirius A, we derive internal structure models corresponding to ages between 200 and 250 +/- 12 Myr. This range is defined mainly by the hypothesis on the mass of the star, the overshoot and the metallicity.Comment: 9 pages, 4 figures, accepted for publication by A&

JIP1-Mediated JNK Activation Negatively Regulates Synaptic Plasticity and Spatial Memory

The c-Jun N-terminal kinase (JNK) signal transduction pathway is implicated in learning and memory. Here, we examined the role of JNK activation mediated by the JIP1 scaffold protein. We compared male wild-type mice with a mouse model harboring a point mutation in the Jip1 gene that selectively blocks JIP1-mediated JNK activation. These male mutant mice exhibited increased NMDA receptor currents, increased NMDA receptor-mediated gene expression, and a lower threshold for induction of hippocampal long-term potentiation. The JIP1 mutant mice also displayed improved hippocampus-dependent spatial memory and enhanced associative fear conditioning. These results were confirmed using a second JIP1 mutant mouse model that suppresses JNK activity. Together, these observations establish that JIP1-mediated JNK activation contributes to the regulation of hippocampus-dependent, NMDA receptor-mediated synaptic plasticity and learning. SIGNIFICANCE STATEMENT: The results of this study demonstrate that JNK activation induced by the JIP1 scaffold protein negatively regulates the threshold for induction of long-term synaptic plasticity through the NMDA-type glutamate receptor. This change in plasticity threshold influences learning. Indeed, mice with defects in JIP1-mediated JNK activation display enhanced memory in hippocampus-dependent tasks, such as contextual fear conditioning and Morris water maze, indicating that JIP1-JNK constrains spatial memory. This study reports the identification of JIP1-mediated JNK activation as a novel molecular pathway that negatively regulates NMDA receptor-dependent synaptic plasticity and memory

Light bosons and photospheric solutions to the solar abundance problem

It is well known that current spectroscopic determinations of the chemical composition of the Sun are starkly at odds with the metallicity implied by helioseismology. We investigate whether the discrepancy may be due to conversion of photons to a new light boson in the solar photosphere. We examine the impact of particles with axion-like interactions with the photon on the inferred photospheric abundances, showing that resonant axion-photon conversion is not possible in the region of the solar atmosphere in which line-formation occurs. Although non-resonant conversion in the line-forming regions can in principle impact derived abundances, constraints from axion-photon conversion experiments rule out the couplings necessary for these effects to be detectable. We show that this extends to hidden photons and chameleons (which would exhibit similar phenomenological behaviour), ruling out known theories of new light bosons as photospheric solutions to the solar abundance problem.Comment: 11 pages, PDFLaTeX. v2: Major revision. Inclusion of refractive index effect on photon-ALP conversion strengthens our conclusion that such an effect cannot explain the solar abundance problem with a coupling allowed by experimental axion-like particle searches. We now include a discussion of chameleons and hidden photons, with similar conclusion

The radius and other fundamental parameters of the F9 V star beta Virginis

We have used the Sydney University Stellar Interferometer (SUSI) to measure the angular diameter of the F9 V star beta Virginis. After correcting for limb darkening and combining with the revised Hipparcos parallax, we derive a radius of 1.703 +/- 0.022 R_sun (1.3%). We have also calculated the bolometric flux from published measurements which, combined with the angular diameter, implies an effective temperature of 6059 +/- 49 K (0.8%). We also derived the luminosity of beta Vir to be L = 3.51 +/- 0.08 L_sun (2.1%). Solar-like oscillations were measured in this star by Carrier et al. (2005) and using their value for the large frequency separation yields the mean stellar density with an uncertainty of about 2%. Our constraints on the fundamental parameters of beta Vir will be important to test theoretical models of this star and its oscillations.Comment: accepted for publication in MNRAS. Updated reference