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PN: GOing Bayesian: model-based gene set analysis of genome-scale data
- Nucleic Acids Res
"... The interpretation of data-driven experiments in genomics often involves a search for biological categories that are enriched for the responder genes identified by the experiments. However, knowledge bases such as the Gene Ontology (GO) contain hundreds or thousands of categories with very high over ..."
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The interpretation of data-driven experiments in genomics often involves a search for biological categories that are enriched for the responder genes identified by the experiments. However, knowledge bases such as the Gene Ontology (GO) contain hundreds or thousands of categories with very high overlap between categories. Thus, enrich-ment analysis performed on one category at a time frequently returns large numbers of correlated categories, leaving the choice of the most relevant ones to the user’s interpretation. Here we present model-based gene set analysis (MGSA) that analyzes all categories at once by embedding them in a Bayesian network, in which gene response is modeled as a function of the acti-vation of biological categories. Probabilistic inference is used to identify the active categories. The Bayesian modeling approach naturally takes category over-lap into account and avoids the need for multiple testing corrections met in single-category enrich-ment analysis. On simulated data, MGSA identifies active categories with up to 95 % precision at a recall of 20 % for moderate settings of noise, leading to a 10-fold precision improvement over single-category statistical enrichment analysis. Application to a gene expression data set in yeast demonstrates that the method provides high-level, summarized views of core biological processes and correctly eliminates confounding associations.
Review Bench-to-bedside review: Mitochondrial injury, oxidative stress and apoptosis – there is nothing more practical than a good theory
, 2008
"... Apoptosis contributes to cell death in common intensive care unit disorders such as traumatic brain injury and sepsis. Recent evidence suggests that this form of cell death is both clinically relevant and a potential therapeutic target in critical illness. Mitochondrial reactive oxygen species (ROS) ..."
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Apoptosis contributes to cell death in common intensive care unit disorders such as traumatic brain injury and sepsis. Recent evidence suggests that this form of cell death is both clinically relevant and a potential therapeutic target in critical illness. Mitochondrial reactive oxygen species (ROS) have become a target for drug discovery in recent years since their production is characteristic of early stages of apoptosis. Among many antioxidant agents, stable nitroxide radicals targeted to mitochondria have attracted attention due to their ability to combine electron and free radical scavenging action with recycling capacities. Specific mechanisms of enhanced ROS generation in mitochondria and their translation into apoptotic signals are not well understood. This review focuses on several contemporary aspects of oxidative stress-mediated mitochondrial injury, particularly as they relate to oxidation of lipids
Mitochondrial complex I defect induces ROS release and degeneration in trabecular meshwork cells of POAG patients: protection by antioxidants. Invest Ophthalmol Vis Sci 49
, 2008
"... PURPOSE. There is growing evidence that oxidative stress contributes to the progression of primary open-angle glaucoma (POAG), a leading cause of irreversible blindness worldwide. The authors provide evidence that mitochondrial dysfunction is a possible mechanism for the loss of trabecular meshwork ..."
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Cited by 12 (0 self)
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PURPOSE. There is growing evidence that oxidative stress contributes to the progression of primary open-angle glaucoma (POAG), a leading cause of irreversible blindness worldwide. The authors provide evidence that mitochondrial dysfunction is a possible mechanism for the loss of trabecular meshwork (TM) cells in persons with POAG. METHODS. TM from patients with POAG (GTM) and agematched subjects without disease (NTM) were obtained by standard surgical trabeculectomy. Primary TM cultures were treated with one of the following mitochondrial respiratory chain inhibitors: rotenone (ROT, complex I inhibitor), thenoyltrifluoroacetone (TTFA, complex II inhibitor), myxothiazol or antimycin A (MYX, AM-complex III inhibitors); mitochondrial permeability transition (MPT) inhibitor cyclosporine A (CsA); and antioxidants vitamin E (Vit E) or N-acetylcysteine (NAC).
Phosphoproteome analysis of functional mitochondria isolated from resting human muscle reveals extensive phosphorylation of inner membrane protein complexes and enzymes
- Mol. Cell. Proteomics
, 2011
"... Mitochondria play a central role in energy metabolism and cellular survival, and consequently mitochondrial dys-function is associated with a number of human patholo-gies. Reversible protein phosphorylation emerges as a central mechanism in the regulation of several mitochon-drial processes. In skel ..."
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Mitochondria play a central role in energy metabolism and cellular survival, and consequently mitochondrial dys-function is associated with a number of human patholo-gies. Reversible protein phosphorylation emerges as a central mechanism in the regulation of several mitochon-drial processes. In skeletal muscle, mitochondrial dys-function is linked to insulin resistance in humans with obesity and type 2 diabetes. We performed a phospho-proteomics study of functional mitochondria isolated from human muscle biopsies with the aim to obtain a comprehensive overview of mitochondrial phosphopro-teins. Combining an efficient mitochondrial isolation pro-tocol with several different phosphopeptide enrichment techniques and LC-MS/MS, we identified 155 distinct phosphorylation sites in 77 mitochondrial phosphopro-
The Vaccinia Virus F1L Protein Interacts with the Proapoptotic Protein Bak and Inhibits Bak Activation
, 2005
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Honokiol Induces a Necrotic Cell Death through the Mitochondrial Permeability Transition Pore
, 2007
"... Access the most recent version of this article at: doi: 10.1158/0008-5472.CAN-06-3818 Access the most recent supplemental material at: ..."
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Cited by 8 (0 self)
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Access the most recent version of this article at: doi: 10.1158/0008-5472.CAN-06-3818 Access the most recent supplemental material at:
Poliovirus Induces Bax-Dependent Cell Death Mediated by c-Jun
, 2006
"... These include: This article cites 76 articles, 38 of which can be accessed free at: ..."
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Cited by 8 (2 self)
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These include: This article cites 76 articles, 38 of which can be accessed free at:
Switch from type II to I Fas/CD95 death signaling on in vitro culturing of primary hepatocytes. Hepatology 48:1942–1953
- McNelly S, von Weizsäcker F, Merfort I, Maurer U, Strasser A, Borner C
, 2008
"... primary hepatocytes ..."
Caloric restriction delays cardiac ageing in rats: role of mitochondria. Cardiovasc Res 88:267–276
, 2010
"... of mitochondria ..."
Suppression of endoplasmic reticulum stress-induced caspase activation and cell death by the overexpression of Bcl-xL or Bcl-2
- J Biochem (Tokyo
, 2007
"... Continuous endoplasmic reticulum (ER) stress, such as the accumulation of unfolded proteins, results in cell death and relates to the pathogenesis of some neurodegenerative diseases. Treatment of brefeldin A, an inhibitor of transport between the ER and Golgi complex, induced cell death during 24h, ..."
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Continuous endoplasmic reticulum (ER) stress, such as the accumulation of unfolded proteins, results in cell death and relates to the pathogenesis of some neurodegenerative diseases. Treatment of brefeldin A, an inhibitor of transport between the ER and Golgi complex, induced cell death during 24h, which accompanied activation of caspase-2, caspase-3 and caspase-9, starting at 12h and increasing time-dependently up to 28h. Caspase-2 was expressed and activated in not only mitochondria and cytosol, but also in the microsomal fraction containing ER and Golgi. Of note is that overexpression of Bcl-xL or Bcl-2 in PC12 cells markedly suppressed brefeldin A-induced activation of caspases and resulting cell death. Delivery of anti-Bcl-2 antibody into the Bcl-2-overexpressed cells again recovered apoptosis. While the brefeldin A-treatment induced the phosphorylation of both c-Jun N-terminal kinase (JNK) and p38 MAPK, overexpression of Bcl-xL or Bcl-2 reduced the prolonged phosphorylation of JNK, but not of p38 MAPK. Pretreatment with a JNK inhibitor, SP600125, suppressed the brefeldin A-induced caspase-2 activation and cell death significantly. Thus, our results suggest that protective
