188 research outputs found
Cell Size and Shape
No full textSéminaire FSER organisé par Michael Hall (Biozentrum, Basel) et David Sabatini (Whitehead Institute, USA) du 9 au 15 mai 2005 Participants Joseph Avruch, Yves-Alain Barde, John Blenis, David Carling, Marian Carlson, Bruce A. Edgard, Rick Firtel, Kun-Liang Guan, Michael N. Hall, Pierre Léopold, Thomas P. Neufeld, Marius Pende, Matthias Peter, Jacques Pouyssegur, Anne Ridley, David D. Sabatini, Nahum Sonenberg, James Umen, Anders Zetterberg Résumé La croissance cellulaire est, avec la proliféra..
MAP kinase pathways: The first twenty years
No full textAbstractThe MAP kinases, discovered approximately 20 years ago, together with their immediate upstream regulators, are among the most highly studied signal transduction molecules. This body of work has shaped many aspects of our present views of signal transduction by protein kinases. The effort expended in this area reflects the extensive participation of these regulatory modules in the control of cell fate decisions, i.e., proliferation, differentiation and death, across all eukaryotic phylla and in all tissues of metazoans. The discovery of these kinases is reviewed, followed by a discussion of some of the features of this signaling module that account for its broad impact on cell function and its enormous interest to many investigators
Rents and Protests in the Sultanate of Oman
No full textThis thesis uses rentier state theory (RST) as a framework for understanding the origins of the protest movement in the Sultanate of Oman during the so-called Arab Uprisings. The discussion will focus on the evolution of RST, historic and cultural factors related to the Sultanate’s modern development, and the unique characteristics of Oman’s political economy, especially during the 2003 to 2013 timeframe. It will argue the rentier state model has led to dual dependencies: oil for revenue and expatriates for labor. These dual dependencies have created real economic conditions that differ substantially from the publicly stated goals of the Omani government and have led to the grievances expressed by Omanis during the 2011 protest movement. Using a mixed methods approach and relying on original in-country research conducted by the author from April to June 2014, the research will demonstrate the protest movement occurred not simply because of a region-wide contagion effect, but because of the underlying characteristics defining Oman’s political economy
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Mitochondrial Triggers of the Integrated Stress Response: Disentangling the Bioenergetic Rubik’s Cube
No full textMitochondria are hubs of metabolism and signaling in eukaryotic cells whose dysfunction underlies a class of devastating genetic disorders and is also frequently associated with common conditions, such as neurodegeneration, diabetes, cancer and the ageing process. Mitochondrial dysfunction, particularly breakdown of the electron transport chain (ETC) and oxidative phosphorylation, yields a perplexingly variable spectrum of consequences at the cellular, tissue and whole-organism level. Deciphering the context-dependent pathophysiology of mitochondrial dysfunction is thus a major challenge in both basic and translational biomedical research.
Studies over the past decade have revealed that a prominent molecular signature of mitochondrial dysfunction in vivo is activation of the integrated stress response (ISR), a gene expression program eukaryotic cells engage upon different types of insults. How mitochondrial dysfunction is sensed to trigger the ISR and whether the response serves a protective role or contributes to pathology remain far from understood.
The work in this thesis sought to delineate functional parameters tied to the ETC, such as ATP synthesis or NADH oxidation, that can lead to ISR activation. We used chemical and genetic tools to perturb ETC functions in mouse muscle cells while specifically compensating for some of the resulting metabolic effects. We then monitored the impact of these interventions on ISR-dependent gene expression by RNA sequencing.
Our results revealed that in proliferating cells, the increase in the cytosolic [NADH]/[NAD+] ratio during complex I dysfunction potently triggered the ISR, mostly by sharply depressing aspartate levels and activating the amino acid sensitive eIF2α kinase GCN2. Strikingly, this route to ISR activation became inoperative in terminally-differentiated myotubes where only ATP synthase inhibition elicited a significant response. The path to ISR activation in the latter case was dependent on residual ETC activity and could be abolished by co-inhibition of complex I, mild uncoupling or mild hypoxic preconditioning. Finally, our data suggests dysfunction of mitochondrial genome expression is not directly sensed to trigger the ISR.
These results shed light on the complicated interplay between mitochondrial dysfunction and the ISR. They implicate diverse metabolic and bioenergetic routes to its activation whose relevance in vivo should be carefully evaluated in future work.Systems Biolog
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Glutamatergic Regulation of the p70S6 Kinase in Primary Mouse Neurons
No full textVersion of Recor
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