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202. Mechatronics Education

Author

van Amerongen, Job, Bradley, David, and Russell, David W.

Subjects
Mechanical construction, Electrical network, Mechatronic systems, Mobile robot, Bond graph
Abstract

This chapter describes the different mechatronic programmes of the last 20 years in the University of Twente.

Published
2010

203. Adeno-associated virus vector integration

Author

Deyle, David R and Russell, David W

Subjects
Cell Nucleus, Recombination, Genetic, viruses, Virus Integration, Genetic Vectors, Animals, Humans, Genome, Viral, Dependovirus, Article
Abstract

Adeno-associated virus (AAV) vectors efficiently transduce various cell types and can produce long-term expression of transgenes in vivo. Although AAV vector genomes can persist within cells as episomes, vector integration has been observed in various experimental settings, either at non-homologous sites where DNA damage may have occurred or by homologous recombination. In some cases, integration is essential for the therapeutic or experimental efficacy of AAV vectors. Recently, insertional mutagenesis resulting from the integration of AAV vectors was associated with tumorigenesis in mice, a consideration that may have relevance for certain clinical applications.

Published
2009

207. Nuclease-free Adeno-Associated Virus-Mediated Il2rgGene Editing in X-SCID Mice

Author

Hiramoto, Takafumi, Li, Li B., Funk, Sarah E., Hirata, Roli K., and Russell, David W.

Abstract

X-linked severe combined immunodeficiency (X-SCID) has been successfully treated by hematopoietic stem cell (HSC) transduction with retroviral vectors expressing the interleukin-2 receptor subunit gamma gene (IL2RG), but several patients developed malignancies due to vector integration near cellular oncogenes. This adverse side effect could in principle be avoided by accurate IL2RGgene editing with a vector that does not contain a functional promoter or IL2RGgene. Here, we show that adeno-associated virus (AAV) gene editing vectors can insert a partial Il2rgcDNA at the endogenous Il2rglocus in X-SCID murine bone marrow cells and that these ex vivo-edited cells repopulate transplant recipients and produce CD4+and CD8+T cells. Circulating, edited lymphocytes increased over time and appeared in secondary transplant recipients, demonstrating successful editing in long-term repopulating cells. Random vector integration events were nearly undetectable, and malignant transformation of the transplanted cells was not observed. Similar editing frequencies were observed in human hematopoietic cells. Our results demonstrate that therapeutically relevant HSC gene editing can be achieved by AAV vectors in the absence of site-specific nucleases and suggest that this may be a safe and effective therapy for hematopoietic diseases where in vivoselection can increase edited cell numbers.

Published
2018
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209. Lipidomics reveals a remarkable diversity of lipids in human plasma.

Author

Quehenberger, Oswald, Quehenberger, Oswald, Armando, Aaron M, Brown, Alex H, Milne, Stephen B, Myers, David S, Merrill, Alfred H, Bandyopadhyay, Sibali, Jones, Kristin N, Kelly, Samuel, Shaner, Rebecca L, Sullards, Cameron M, Wang, Elaine, Murphy, Robert C, Barkley, Robert M, Leiker, Thomas J, Raetz, Christian RH, Guan, Ziqiang, Laird, Gregory M, Six, David A, Russell, David W, McDonald, Jeffrey G, Subramaniam, Shankar, Fahy, Eoin, Dennis, Edward A, Quehenberger, Oswald, Quehenberger, Oswald, Armando, Aaron M, Brown, Alex H, Milne, Stephen B, Myers, David S, Merrill, Alfred H, Bandyopadhyay, Sibali, Jones, Kristin N, Kelly, Samuel, Shaner, Rebecca L, Sullards, Cameron M, Wang, Elaine, Murphy, Robert C, Barkley, Robert M, Leiker, Thomas J, Raetz, Christian RH, Guan, Ziqiang, Laird, Gregory M, Six, David A, Russell, David W, McDonald, Jeffrey G, Subramaniam, Shankar, Fahy, Eoin, and Dennis, Edward A

Abstract

The focus of the present study was to define the human plasma lipidome and to establish novel analytical methodologies to quantify the large spectrum of plasma lipids. Partial lipid analysis is now a regular part of every patient's blood test and physicians readily and regularly prescribe drugs that alter the levels of major plasma lipids such as cholesterol and triglycerides. Plasma contains many thousands of distinct lipid molecular species that fall into six main categories including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterols, and prenols. The physiological contributions of these diverse lipids and how their levels change in response to therapy remain largely unknown. As a first step toward answering these questions, we provide herein an in-depth lipidomics analysis of a pooled human plasma obtained from healthy individuals after overnight fasting and with a gender balance and an ethnic distribution that is representative of the US population. In total, we quantitatively assessed the levels of over 500 distinct molecular species distributed among the main lipid categories. As more information is obtained regarding the roles of individual lipids in health and disease, it seems likely that future blood tests will include an ever increasing number of these lipid molecules.

Published
2010

210. Subcellular organelle lipidomics in TLR-4-activated macrophages.

Author

Andreyev, Alexander Y, Andreyev, Alexander Y, Fahy, Eoin, Guan, Ziqiang, Kelly, Samuel, Li, Xiang, McDonald, Jeffrey G, Milne, Stephen, Myers, David, Park, Hyejung, Ryan, Andrea, Thompson, Bonne M, Wang, Elaine, Zhao, Yihua, Brown, H Alex, Merrill, Alfred H, Raetz, Christian RH, Russell, David W, Subramaniam, Shankar, Dennis, Edward A, Andreyev, Alexander Y, Andreyev, Alexander Y, Fahy, Eoin, Guan, Ziqiang, Kelly, Samuel, Li, Xiang, McDonald, Jeffrey G, Milne, Stephen, Myers, David, Park, Hyejung, Ryan, Andrea, Thompson, Bonne M, Wang, Elaine, Zhao, Yihua, Brown, H Alex, Merrill, Alfred H, Raetz, Christian RH, Russell, David W, Subramaniam, Shankar, and Dennis, Edward A

Abstract

Lipids orchestrate biological processes by acting remotely as signaling molecules or locally as membrane components that modulate protein function. Detailed insight into lipid function requires knowledge of the subcellular localization of individual lipids. We report an analysis of the subcellular lipidome of the mammalian macrophage, a cell type that plays key roles in inflammation, immune responses, and phagocytosis. Nuclei, mitochondria, endoplasmic reticulum (ER), plasmalemma, and cytoplasm were isolated from RAW 264.7 macrophages in basal and activated states. Subsequent lipidomic analyses of major membrane lipid categories identified 229 individual/isobaric species, including 163 glycerophospholipids, 48 sphingolipids, 13 sterols, and 5 prenols. Major subcellular compartments exhibited substantially divergent glycerophospholipid profiles. Activation of macrophages by the Toll-like receptor 4-specific lipopolysaccharide Kdo(2)-lipid A caused significant remodeling of the subcellular lipidome. Some changes in lipid composition occurred in all compartments (e.g., increases in the levels of ceramides and the cholesterol precursors desmosterol and lanosterol). Other changes were manifest in specific organelles. For example, oxidized sterols increased and unsaturated cardiolipins decreased in mitochondria, whereas unsaturated ether-linked phosphatidylethanolamines decreased in the ER. We speculate that these changes may reflect mitochondrial oxidative stress and the release of arachidonic acid from the ER in response to cell activation.

Published
2010

211. A mouse macrophage lipidome.

Author

Dennis, Edward A, Dennis, Edward A, Deems, Raymond A, Harkewicz, Richard, Quehenberger, Oswald, Brown, H Alex, Milne, Stephen B, Myers, David S, Glass, Christopher K, Hardiman, Gary, Reichart, Donna, Merrill, Alfred H, Sullards, M Cameron, Wang, Elaine, Murphy, Robert C, Raetz, Christian RH, Garrett, Teresa A, Guan, Ziqiang, Ryan, Andrea C, Russell, David W, McDonald, Jeffrey G, Thompson, Bonne M, Shaw, Walter A, Sud, Manish, Zhao, Yihua, Gupta, Shakti, Maurya, Mano R, Fahy, Eoin, Subramaniam, Shankar, Dennis, Edward A, Dennis, Edward A, Deems, Raymond A, Harkewicz, Richard, Quehenberger, Oswald, Brown, H Alex, Milne, Stephen B, Myers, David S, Glass, Christopher K, Hardiman, Gary, Reichart, Donna, Merrill, Alfred H, Sullards, M Cameron, Wang, Elaine, Murphy, Robert C, Raetz, Christian RH, Garrett, Teresa A, Guan, Ziqiang, Ryan, Andrea C, Russell, David W, McDonald, Jeffrey G, Thompson, Bonne M, Shaw, Walter A, Sud, Manish, Zhao, Yihua, Gupta, Shakti, Maurya, Mano R, Fahy, Eoin, and Subramaniam, Shankar

Abstract

We report the lipidomic response of the murine macrophage RAW cell line to Kdo(2)-lipid A, the active component of an inflammatory lipopolysaccharide functioning as a selective TLR4 agonist and compactin, a statin inhibitor of cholesterol biosynthesis. Analyses of lipid molecular species by dynamic quantitative mass spectrometry and concomitant transcriptomic measurements define the lipidome and demonstrate immediate responses in fatty acid metabolism represented by increases in eicosanoid synthesis and delayed responses characterized by sphingolipid and sterol biosynthesis. Lipid remodeling of glycerolipids, glycerophospholipids, and prenols also take place, indicating that activation of the innate immune system by inflammatory mediators leads to alterations in a majority of mammalian lipid categories, including unanticipated effects of a statin drug. Our studies provide a systems-level view of lipid metabolism and reveal significant connections between lipid and cell signaling and biochemical pathways that contribute to innate immune responses and to pharmacological perturbations.

Published
2010

212. A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome

Author

Buchovecky, Christie M, primary, Turley, Stephen D, additional, Brown, Hannah M, additional, Kyle, Stephanie M, additional, McDonald, Jeffrey G, additional, Liu, Benny, additional, Pieper, Andrew A, additional, Huang, Wenhui, additional, Katz, David M, additional, Russell, David W, additional, Shendure, Jay, additional, and Justice, Monica J, additional

Published
2013
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213. Christian Raetz: Scientist and Friend Extraordinaire

Author

Dowhan, William, primary, Nikaido, Hiroshi, additional, Stubbe, JoAnne, additional, Kozarich, John W., additional, Wickner, William T., additional, Russell, David W., additional, Garrett, Teresa A., additional, Brozek, Kathryn, additional, and Modrich, Paul, additional

Published
2013
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214. HLA Engineering of Human Pluripotent Stem Cells

Author

Riolobos, Laura, primary, Hirata, Roli K, additional, Turtle, Cameron J, additional, Wang, Pei-Rong, additional, Gornalusse, German G, additional, Zavajlevski, Maja, additional, Riddell, Stanley R, additional, and Russell, David W, additional

Published
2013
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217. Disruption of Cholesterol 7α-Hydroxylase Gene in Mice: II. BILE ACID DEFICIENCY IS OVERCOME BY INDUCTION OF OXYSTEROL 7α-HYDROXYLASE*

Author

Schwarz, Margrit, Lund, Erik G., Setchell, Kenneth D. R., Kayden, Herbert J., Zerwekh, Joseph E., Björkhem, Ingemar, Herz, Joachim, and Russell, David W.

Subjects
Mice, Knockout, Lipoproteins, Age Factors, Article, Mitochondria, Bile Acids and Salts, Feces, Mice, Cholesterol, Phenotype, Cytochrome P-450 Enzyme System, Enzyme Induction, Microsomes, Steroid Hydroxylases, Animals, Bile, Vitamin E, lipids (amino acids, peptides, and proteins), Female, Cholesterol 7-alpha-Hydroxylase, Triglycerides, Cholecalciferol
Abstract

Past experiments and current paradigms of cholesterol homeostasis suggest that cholesterol 7alpha-hydroxylase plays a crucial role in sterol metabolism by controlling the conversion of cholesterol into bile acids. Consistent with this conclusion, we show in the accompanying paper that mice deficient in cholesterol 7alpha-hydroxylase (Cyp7-/- mice) exhibit a complex phenotype consisting of abnormal lipid excretion, skin pathologies, and behavioral irregularities (Ishibashi, S., Schwarz, M., Frykman, P. K. , Herz, J., and Russell, D. W.(1996) J. Biol. Chem. 261, 18017-18023). Aspects of lipid metabolism in the Cyp7-/- mice are characterized here to deduce the physiological basis of this phenotype. Serum lipid, cholesterol, and lipoprotein contents are indistinguishable between wild-type and Cyp7-/- mice. Vitamin D3 and E levels are low to undetectable in knockout animals. Stool fat content is significantly elevated in newborn Cyp7-/- mice and gradually declines to wild-type levels at 28 days of age. Several species of 7alpha-hydroxylated bile acids are detected in the bile and stool of adult Cyp7-/- animals. A hepatic oxysterol 7alpha-hydroxylase enzyme activity that may account for the 7alpha-hydroxylated bile acids is induced between days 21 and 30 in both wild-type and deficient mice. An anomalous oily coat in the Cyp7-/- animals is due to the presence of excess monoglyceride esters in the fur. These data show that 7alpha-hydroxylase and the pathway of bile acid synthesis initiated by this enzyme are essential for proper absorption of dietary lipids and fat-soluble vitamins in newborn mice, but not for the maintenance of serum cholesterol and lipid levels. In older animals, an alternate pathway of bile acid synthesis involving an inducible oxysterol 7alpha-hydroxylase plays a crucial role in lipid and bile acid metabolism.

Published
1996

218. A comprehensive classification system for lipids.

Author

Fahy, Eoin, Fahy, Eoin, Subramaniam, Shankar, Brown, H Alex, Glass, Christopher K, Merrill, Alfred H, Murphy, Robert C, Raetz, Christian RH, Russell, David W, Seyama, Yousuke, Shaw, Walter, Shimizu, Takao, Spener, Friedrich, van Meer, Gerrit, VanNieuwenhze, Michael S, White, Stephen H, Witztum, Joseph L, Dennis, Edward A, Fahy, Eoin, Fahy, Eoin, Subramaniam, Shankar, Brown, H Alex, Glass, Christopher K, Merrill, Alfred H, Murphy, Robert C, Raetz, Christian RH, Russell, David W, Seyama, Yousuke, Shaw, Walter, Shimizu, Takao, Spener, Friedrich, van Meer, Gerrit, VanNieuwenhze, Michael S, White, Stephen H, Witztum, Joseph L, and Dennis, Edward A

Abstract

Lipids are produced, transported, and recognized by the concerted actions of numerous enzymes, binding proteins, and receptors. A comprehensive analysis of lipid molecules, "lipidomics," in the context of genomics and proteomics is crucial to understanding cellular physiology and pathology; consequently, lipid biology has become a major research target of the postgenomic revolution and systems biology. To facilitate international communication about lipids, a comprehensive classification of lipids with a common platform that is compatible with informatics requirements has been developed to deal with the massive amounts of data that will be generated by our lipid community. As an initial step in this development, we divide lipids into eight categories (fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, prenol lipids, saccharolipids, and polyketides) containing distinct classes and subclasses of molecules, devise a common manner of representing the chemical structures of individual lipids and their derivatives, and provide a 12 digit identifier for each unique lipid molecule. The lipid classification scheme is chemically based and driven by the distinct hydrophobic and hydrophilic elements that compose the lipid. This structured vocabulary will facilitate the systematization of lipid biology and enable the cataloging of lipids and their properties in a way that is compatible with other macromolecular databases.

Published
2005

219. Alfresco reflections

Author

Chiaverina, Christopher and Russell, David W>

Subjects
Shades and shadows -- Tests, problems and exercises, Education, Physics
Published
2010

226. Detecting oxysterols in the human circulation

Author

Björkhem, Ingemar, primary, Diczfalusy, Ulf, additional, Olsson, Tomas, additional, Russell, David W, additional, McDonald, Jeffery G, additional, Wang, Yuqin, additional, and Griffiths, William J, additional

Published
2011
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233. A Mouse Macrophage Lipidome

Author

Dennis, Edward A., primary, Deems, Raymond A., additional, Harkewicz, Richard, additional, Quehenberger, Oswald, additional, Brown, H. Alex, additional, Milne, Stephen B., additional, Myers, David S., additional, Glass, Christopher K., additional, Hardiman, Gary, additional, Reichart, Donna, additional, Merrill, Alfred H., additional, Sullards, M. Cameron, additional, Wang, Elaine, additional, Murphy, Robert C., additional, Raetz, Christian R.H., additional, Garrett, Teresa A., additional, Guan, Ziqiang, additional, Ryan, Andrea C., additional, Russell, David W., additional, McDonald, Jeffrey G., additional, Thompson, Bonne M., additional, Shaw, Walter A., additional, Sud, Manish, additional, Zhao, Yihua, additional, Gupta, Shakti, additional, Maurya, Mano R., additional, Fahy, Eoin, additional, and Subramaniam, Shankar, additional

Published
2010
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234. Lipidomics reveals a remarkable diversity of lipids in human plasma

Author

Quehenberger, Oswald, primary, Armando, Aaron M., additional, Brown, Alex H., additional, Milne, Stephen B., additional, Myers, David S., additional, Merrill, Alfred H., additional, Bandyopadhyay, Sibali, additional, Jones, Kristin N., additional, Kelly, Samuel, additional, Shaner, Rebecca L., additional, Sullards, Cameron M., additional, Wang, Elaine, additional, Murphy, Robert C., additional, Barkley, Robert M., additional, Leiker, Thomas J., additional, Raetz, Christian R.H., additional, Guan, Ziqiang, additional, Laird, Gregory M., additional, Six, David A., additional, Russell, David W., additional, McDonald, Jeffrey G., additional, Subramaniam, Shankar, additional, Fahy, Eoin, additional, and Dennis, Edward A., additional

Published
2010
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236. Subcellular organelle lipidomics in TLR-4-activated macrophages

Author

Andreyev, Alexander Y., primary, Fahy, Eoin, additional, Guan, Ziqiang, additional, Kelly, Samuel, additional, Li, Xiang, additional, McDonald, Jeffrey G., additional, Milne, Stephen, additional, Myers, David, additional, Park, Hyejung, additional, Ryan, Andrea, additional, Thompson, Bonne M., additional, Wang, Elaine, additional, Zhao, Yihua, additional, Brown, H. Alex, additional, Merrill, Alfred H., additional, Raetz, Christian R.H., additional, Russell, David W., additional, Subramaniam, Shankar, additional, and Dennis, Edward A., additional

Published
2010
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242. A Sharper Focus on Constant Transformation.

Author

Foster, Martin and Russell, David W.

Subjects
ORGANIZATIONAL change, BUSINESS planning, CAMERA industry, VIDEO recording equipment
Abstract

The article discusses the chief executive officer (CEO) Fujio Mitarai, of the Japanese corporation and camera manufacturer Canon Incorporated, including the changes that the company has undertaken and its development of video recording equipment. An overview of its five-year plan known as the Excellent Global Corporation Plan, including the goal of developing medical equipment to be sold throughout the world, is provided.

Published
2017

248. Reduced Genotoxicity of Avian Sarcoma Leukosis Virus Vectors in Rhesus Long-term Repopulating Cells Compared to Standard Murine Retrovirus Vectors

Author

Hu, Jingqiong, primary, Renaud, Gabriel, additional, Golmes, Theotonius, additional, Ferris, Andrea, additional, Hendrie, Paul C, additional, Donahue, Robert E, additional, Hughes, Stephen H, additional, Wolfsberg, Tyra G, additional, Russell, David W, additional, and Dunbar, Cynthia E, additional

Published
2008
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