Wepreviously developedSKI-178 (N9-[(1E)-1-(3,4-dimethoxyphenyl) ethylidene]-3-(4-methoxxyphenyl)-1H-pyrazole-5-carbohydrazide) as a novel sphingosine kinase-1 (SphK1) selective inhibitor and, herein, sought to determine the mechanism-of-action of SKI178–induced cell death. Using human acute myeloid leukemia (AML) cell lines as a model, we present evidence that SKI-178 induces prolonged mitosis ...

c-Ski is a transcriptional corepressor that interacts strongly with Smad2, Smad3, and Smad4 but only weakly with Smad1 and Smad5. Through binding to Smad proteins, c-Ski suppresses signaling of transforming growth factor-beta (TGF-beta) as well as bone morphogenetic proteins (BMPs). In the present study, we found that a mutant of c-Ski, termed c-Ski (ARPG) inhibited TGF-beta/activin signaling b...

Endogenous, constitutive soluble epoxide hydrolase in mice 3T3 cells was localized via immunofluorescence microscopy exclusively in peroxisomes, whereas transiently expressed mouse soluble epoxide hydrolase (from clofibrate-treated liver) accumulated only in the cytosol of 3T3 and HeLa cells. When the C-terminal lie of mouse soluble epoxide hydrolase was mutated to generate a prototypic putativ...

Nordic ski-jumping fatalities are rare events. Six jumping fatalities have occurred in the United States during the past 50 years. The fatality rate for nordic ski jumping, estimated to be roughly 12 fatalities/100,000 participants annually, appears to be within the range of fatality rates for other "risky" outdoor sports. Cervical fractures appear to be the most frequent fatal ski-jumping injury.

UNLABELLED Arenaviruses are emerging viruses including several causative agents of severe hemorrhagic fevers in humans. The advent of next-generation sequencing technology has greatly accelerated the discovery of novel arenavirus species. However, for many of these viruses, only genetic information is available, and their zoonotic disease potential remains unknown. During the arenavirus life cy...

First insights into the molecular programs orchestrating the progression from neural stem cells to cortical projection neurons are emerging. Loss of the transcriptional regulator Ski has been linked to the human 1p36 deletion syndrome, which includes central nervous system defects. Here, we report critical roles for Ski in the maintenance of the neural stem cell pool and the specification of ca...

PURPOSE Src is overexpressed or hyperactivated in a variety of human cancers, including thyroid carcinoma. Src is a central mediator in multiple signaling pathways that are important in oncogenesis and cancer progression. In this study, we evaluated the effects of an Src inhibitor, SKI-606 (bosutinib), in a spontaneous metastatic thyroid cancer model with constitutively activated Src (Thrb(PV/P...

1 Sustainability Observatory of Andorra (OBSA), Pl. Germandat 7, Sant Julià de Lòria AD600, Andorra 2 Pyrenean Institute of Ecology (CSIC), Av. Montañana 1005, Zaragoza 50059, Spain 3 Sustainability Measurement and Modeling Lab (SUMMLab), Universitat Politècnica de Catalunya (UPC), EET, 08222 Barcelona, Spain Abstract: Winter tourism is the main source of income and the driving force of local...

Purpose: Src is overexpressed or hyperactivated in a variety of human cancers, including thyroid carcinoma. Src is a central mediator in multiple signaling pathways that are important in oncogenesis and cancer progression. In this study, we evaluated the effects of an Src inhibitor, SKI-606 (bosutinib), in a spontaneous metastatic thyroid cancer model with constitutively activated Src (ThrbPV/P...

Ski interacting protein (Skip) plays an important role in the transforming activity of both v-Ski and EBNA2 (Epstein-Barr virus encoded latency protein) and is involved in EBNA2 and NotchIC activation of CBF1-repressed promoters. We have previously shown that Skip acts as a transcriptional co-activator on a number of cellular and viral promoters. Here, we report that Skip also interacts with pR...