Militarinone A induces differentiation in PC12 cells via MAP and Akt kinase signal transduction pathways

AbstractThe fungal metabolite militarinone A (MILI A) promotes neurite outgrowth in PC12 cells. This study was conducted to investigate the signaling pathways involved in the cellular differentiation processes induced by the compound, with a focus on cascades implicated with nerve growth factor (NGF)-mediated neuritogenesis. MILI A possessed pronounced amphiphilic properties. The compound rapidly accumulated in the cell membrane and was slowly released into the cytoplasma. In primed PC12 cells, an early activation of protein kinase B (Akt), representing a downstream target of phosphoinositol 3 (PI3) kinase, and a delayed phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), and of transcription factor cAMP responsive element binding protein (CREB) was found. The NGF-dependent activation of c-Jun amino terminal kinase (SAPK/JNK1) was potentiated. Morphological differentiation of cells and the phosphorylation of specific signal molecules were blocked by the MAP kinase (MEK1) inhibitor PD098059, the PI3-kinase (PI3K) inhibitor wortmannin and the adenylyl cyclase inhibitor 9-cyclopentyladenine

Cirrus clouds

Andrew J. Heymsfield, Martina Kramer, Anna Luebke, Phil Brown, Daniel J. Cziczo, Charmaine Franklin, Ulrike Lohmann, Greg McFarquhar, Zbigniew Ulanowski and Kristof Van Trich, American Meteorological Society , January 2017, this article has been published in final form at DOI: http://dx.doi.org/10.1175/AMSMONOGRAPHS-D-16-0010.1 Published by AMS Publications © 2017 American Meteorological Society. For information regarding reuse of this content and general copyright information, consult the AMS Copyright Policy (http://www.ametsoc.org/PUBSCopyrightPolicy).The goal of this article is to synthesize information about what is now known about one of the three main types of clouds, cirrus, and to identify areas where more knowledge is needed. Cirrus clouds, composed of ice particles, form primarily in the upper troposphere, where temperatures are generally below -30°C. Satellite observations show that the maximum-occurrence frequency of cirrus is near the tropics, with a large latitudinal movement seasonally. In-situ measurements obtained over a wide range of cloud types, formation mechanisms, temperatures, and geographical locations indicate that the ice water content and particle size generally decrease with decreasing temperature, whereas the ice particle concentration is nearly constant or increase slightly with decreasing temperature. High ice concentrations, sometimes observed in strong updrafts , results from homogeneous nucleation. The satellite-based and in-situ measurements indicate that cirrus ice crystals typically depart from the simple, idealized geometry for smooth hexagonal shapes, indicating complexity and/or surface roughness. Their shapes significantly impact cirrus radiative properties and feedbacks to climate. Cirrus clouds, one of the most uncertain components of general circulation models (GCM), pose one of the greatest challenges in predicting the rate and geographical pattern of climate change. Improved measurements of the properties and size distributions and surface structure of small ice crystals — about 20 μm, and identifying the dominant ice nucleation process — heterogeneous versus homogeneous ice nucleation, under different cloud dynamical forcings, will lead to a better representation of their properties in GCM and in modeling their current and future effects on climate.Peer reviewe