Activation of JNK1 contributes to dystrophic muscle pathogenesis

AbstractDuchenne Muscular Dystrophy (DMD) originates from deleterious mutations in the dystrophin gene, with a complete loss of the protein product [1, 2]. Subsequently, the disease is manifested in severe striated muscle wasting and death in early adulthood [3]. Dystrophin provides a structural base for the assembly of an integral membrane protein complex [4]. As such, dystrophin deficiency leads to an altered mechanical integrity of the myofiber and a predisposition to contraction-induced damage [5–7]. However, the development of myofiber degeneration prior to an observed mechanical defect has been documented in various dystrophic models [8, 9]. Although activation of a detrimental signal transduction pathway has been suggested as a probable cause, a specific cellular cascade has yet to be defined. Here, it is shown that murine models of DMD displayed a muscle-specific activation of JNK1. Independent activation of JNK1 resulted in defects in myotube viability and integrity in vitro, similar to a dystrophic phenotype. In addition, direct muscle injection of an adenoviral construct containing the JNK1 inhibitory protein, JIP1, dramatically attenuated the progression of dystrophic myofiber destruction. Taken together, these results suggest that a JNK1-mediated signal cascade is a conserved feature of dystrophic muscle and contributes to the progression of the disease pathogenesis

Argo data 1999-2019: two million temperature-salinity profiles and subsurface velocity observations from a global array of profiling floats.

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Wong, A. P. S., Wijffels, S. E., Riser, S. C., Pouliquen, S., Hosoda, S., Roemmich, D., Gilson, J., Johnson, G. C., Martini, K., Murphy, D. J., Scanderbeg, M., Bhaskar, T. V. S. U., Buck, J. J. H., Merceur, F., Carval, T., Maze, G., Cabanes, C., Andre, X., Poffa, N., Yashayaev, I., Barker, P. M., Guinehut, S., Belbeoch, M., Ignaszewski, M., Baringer, M. O., Schmid, C., Lyman, J. M., McTaggart, K. E., Purkey, S. G., Zilberman, N., Alkire, M. B., Swift, D., Owens, W. B., Jayne, S. R., Hersh, C., Robbins, P., West-Mack, D., Bahr, F., Yoshida, S., Sutton, P. J. H., Cancouet, R., Coatanoan, C., Dobbler, D., Juan, A. G., Gourrion, J., Kolodziejczyk, N., Bernard, V., Bourles, B., Claustre, H., D'Ortenzio, F., Le Reste, S., Le Traon, P., Rannou, J., Saout-Grit, C., Speich, S., Thierry, V., Verbrugge, N., Angel-Benavides, I. M., Klein, B., Notarstefano, G., Poulain, P., Velez-Belchi, P., Suga, T., Ando, K., Iwasaska, N., Kobayashi, T., Masuda, S., Oka, E., Sato, K., Nakamura, T., Sato, K., Takatsuki, Y., Yoshida, T., Cowley, R., Lovell, J. L., Oke, P. R., van Wijk, E. M., Carse, F., Donnelly, M., Gould, W. J., Gowers, K., King, B. A., Loch, S. G., Mowat, M., Turton, J., Rama Rao, E. P., Ravichandran, M., Freeland, H. J., Gaboury, I., Gilbert, D., Greenan, B. J. W., Ouellet, M., Ross, T., Tran, A., Dong, M., Liu, Z., Xu, J., Kang, K., Jo, H., Kim, S., & Park, H. Argo data 1999-2019: two million temperature-salinity profiles and subsurface velocity observations from a global array of profiling floats. Frontiers in Marine Science, 7, (2020): 700, doi:10.3389/fmars.2020.00700.In the past two decades, the Argo Program has collected, processed, and distributed over two million vertical profiles of temperature and salinity from the upper two kilometers of the global ocean. A similar number of subsurface velocity observations near 1,000 dbar have also been collected. This paper recounts the history of the global Argo Program, from its aspiration arising out of the World Ocean Circulation Experiment, to the development and implementation of its instrumentation and telecommunication systems, and the various technical problems encountered. We describe the Argo data system and its quality control procedures, and the gradual changes in the vertical resolution and spatial coverage of Argo data from 1999 to 2019. The accuracies of the float data have been assessed by comparison with high-quality shipboard measurements, and are concluded to be 0.002°C for temperature, 2.4 dbar for pressure, and 0.01 PSS-78 for salinity, after delayed-mode adjustments. Finally, the challenges faced by the vision of an expanding Argo Program beyond 2020 are discussed.AW, SR, and other scientists at the University of Washington (UW) were supported by the US Argo Program through the NOAA Grant NA15OAR4320063 to the Joint Institute for the Study of the Atmosphere and Ocean (JISAO) at the UW. SW and other scientists at the Woods Hole Oceanographic Institution (WHOI) were supported by the US Argo Program through the NOAA Grant NA19OAR4320074 (CINAR/WHOI Argo). The Scripps Institution of Oceanography's role in Argo was supported by the US Argo Program through the NOAA Grant NA15OAR4320071 (CIMEC). Euro-Argo scientists were supported by the Monitoring the Oceans and Climate Change with Argo (MOCCA) project, under the Grant Agreement EASME/EMFF/2015/1.2.1.1/SI2.709624 for the European Commission

Cdk1 Controls Global Epigenetic Landscape in Embryonic Stem Cells

© 2020 Elsevier Inc. The cyclin-dependent kinase 1 (Cdk1) drives cell division. To uncover additional functions of Cdk1, we generated knockin mice expressing an analog-sensitive version of Cdk1 in place of wild-type Cdk1. In our study, we focused on embryonic stem cells (ESCs), because this cell type displays particularly high Cdk1 activity. We found that in ESCs, a large fraction of Cdk1 substrates is localized on chromatin. Cdk1 phosphorylates many proteins involved in epigenetic regulation, including writers and erasers of all major histone marks. Consistent with these findings, inhibition of Cdk1 altered histone-modification status of ESCs. High levels of Cdk1 in ESCs phosphorylate and partially inactivate Dot1l, the H3K79 methyltransferase responsible for placing activating marks on gene bodies. Decrease of Cdk1 activity during ESC differentiation de-represses Dot1l, thereby allowing coordinated expression of differentiation genes. These analyses indicate that Cdk1 functions to maintain the epigenetic identity of ESCs

Students' participation in collaborative research should be recognised

Letter to the editor