subject:(Sphingolipids)

University of Tasmania

1. George, Edwin Ernest. The chemistry and analysis of sphingolipids in natural products.

Degree: 1976, University of Tasmania

URL: https://eprints.utas.edu.au/19789/1/whole_GeorgeEdwinErnest1976_thesis.pdf

► Methods used for the analysis of both synthetic and natural sphingolipids and their components are described. Analytical data is given on ceramides derived from bovine-brain… (more)

Subjects/Keywords: Sphingolipids

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APA (6^th Edition):

George, E. E. (1976). The chemistry and analysis of sphingolipids in natural products. (Thesis). University of Tasmania. Retrieved from https://eprints.utas.edu.au/19789/1/whole_GeorgeEdwinErnest1976_thesis.pdf

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

George, Edwin Ernest. “The chemistry and analysis of sphingolipids in natural products.” 1976. Thesis, University of Tasmania. Accessed February 28, 2021. https://eprints.utas.edu.au/19789/1/whole_GeorgeEdwinErnest1976_thesis.pdf.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

George, Edwin Ernest. “The chemistry and analysis of sphingolipids in natural products.” 1976. Web. 28 Feb 2021.

Vancouver:

George EE. The chemistry and analysis of sphingolipids in natural products. [Internet] [Thesis]. University of Tasmania; 1976. [cited 2021 Feb 28]. Available from: https://eprints.utas.edu.au/19789/1/whole_GeorgeEdwinErnest1976_thesis.pdf.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

George EE. The chemistry and analysis of sphingolipids in natural products. [Thesis]. University of Tasmania; 1976. Available from: https://eprints.utas.edu.au/19789/1/whole_GeorgeEdwinErnest1976_thesis.pdf

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Cornell University

2. Kalkofen, Danielle. A Role For Ceramide Kinase In Membrane Trafficking And Organelle Morphology In Mammalian Cells.

Degree: PhD, Molecular and Cell Biology, 2015, Cornell University

URL: http://hdl.handle.net/1813/39324

► The correct functioning of the cell, and hence a multicellular organism, is dependent on proteins and lipids reaching their proper destination at the correct time.… (more)

▼ The correct functioning of the cell, and hence a multicellular organism, is dependent on proteins and lipids reaching their proper destination at the correct time. Intracellular trafficking is the predominant regulated process by which these materials are transported between various organelles. In route, material is transferred via vesicle and membrane tubule carriers. Previous work from our lab and others have demonstrated that the formation of these carriers are dependent on localized changes in membrane curvature, which is generated by phospholipid modifying enzymes such as lysophospholipid acyltransferases and phospholipid lipases. While our understanding about these carrier intermediates has greatly advanced over the years, many questions remain unanswered. One such question is how cargoes are marked to traffic via a vesicle or a membrane tubule. Aiming to uncover kinase regulators of Golgi membrane tubule formation, our lab conducted a kinome-directed RNAi screen in mammalian cells. Through this screen ceramide kinase, or CERK, was identified as having a positive role in Golgi membrane tubulation. CERK phosphorylates the sphingolipid ceramide to produce ceramide-1-phosphate (C1P). The studies to date indicate CERK and/or C1P may have roles in eicosanoid production and phagolysosome function. However it is unclear whether this is a direct effect of CERK/C1P or is secondary to more fundamental changes in intracellular functions and pathways as indicated by our RNAi screen. The role of CERK in intracellular endolysosomal trafficking and membrane tubulation at the Golgi complex and early endosomes were investigated. By utilizing overexpression and knockdown experiments in conjunction with microscopy-based trafficking assays in mammalian cells, I discovered that CERK activity positively affects membrane tubulation at the Golgi complex and early endosomes. Furthermore, CERK influences endolysosomal morphology without affecting compartment identity, through both catalytic and non-catalytic means. Finally, CERK negatively influences the endocytic trafficking of cholera toxin. Evidence from my studies adds to our understanding of CERK function and will aid in directing future research into the specific biological roles of CERK. Ultimately, further studies are warranted to refine our knowledge regarding CERK function in intracellular trafficking and membrane tubulation. Advisors/Committee Members: Brown, William J (chair), Cerione, Richard A (committee member), Feigenson, Gerald W. (committee member).

Subjects/Keywords: ceramide kinase; membrane trafficking; sphingolipids

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kalkofen, D. (2015). A Role For Ceramide Kinase In Membrane Trafficking And Organelle Morphology In Mammalian Cells. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/39324

Chicago Manual of Style (16^th Edition):

Kalkofen, Danielle. “A Role For Ceramide Kinase In Membrane Trafficking And Organelle Morphology In Mammalian Cells.” 2015. Doctoral Dissertation, Cornell University. Accessed February 28, 2021. http://hdl.handle.net/1813/39324.

MLA Handbook (7^th Edition):

Kalkofen, Danielle. “A Role For Ceramide Kinase In Membrane Trafficking And Organelle Morphology In Mammalian Cells.” 2015. Web. 28 Feb 2021.

Vancouver:

Kalkofen D. A Role For Ceramide Kinase In Membrane Trafficking And Organelle Morphology In Mammalian Cells. [Internet] [Doctoral dissertation]. Cornell University; 2015. [cited 2021 Feb 28]. Available from: http://hdl.handle.net/1813/39324.

Council of Science Editors:

Kalkofen D. A Role For Ceramide Kinase In Membrane Trafficking And Organelle Morphology In Mammalian Cells. [Doctoral Dissertation]. Cornell University; 2015. Available from: http://hdl.handle.net/1813/39324

University of Toronto

3. Melland-Smith, Megan. The Dynamic Role of Sphingolipids and their Regulatory Enzymes in Preeclampsia.

Degree: 2012, University of Toronto

URL: http://hdl.handle.net/1807/67212

►

Sphingolipids act as regulators of cell fate decisions. Ceramides (CERs) are key effector molecules regulating cell death. CERs metabolism is controlled by a balance between… (more)

Subjects/Keywords: Placenta; Sphingolipids; Preeclampsia; 0719

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APA (6^th Edition):

Melland-Smith, M. (2012). The Dynamic Role of Sphingolipids and their Regulatory Enzymes in Preeclampsia. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/67212

Chicago Manual of Style (16^th Edition):

Melland-Smith, Megan. “The Dynamic Role of Sphingolipids and their Regulatory Enzymes in Preeclampsia.” 2012. Masters Thesis, University of Toronto. Accessed February 28, 2021. http://hdl.handle.net/1807/67212.

MLA Handbook (7^th Edition):

Melland-Smith, Megan. “The Dynamic Role of Sphingolipids and their Regulatory Enzymes in Preeclampsia.” 2012. Web. 28 Feb 2021.

Vancouver:

Melland-Smith M. The Dynamic Role of Sphingolipids and their Regulatory Enzymes in Preeclampsia. [Internet] [Masters thesis]. University of Toronto; 2012. [cited 2021 Feb 28]. Available from: http://hdl.handle.net/1807/67212.

Council of Science Editors:

Melland-Smith M. The Dynamic Role of Sphingolipids and their Regulatory Enzymes in Preeclampsia. [Masters Thesis]. University of Toronto; 2012. Available from: http://hdl.handle.net/1807/67212

4. E. Chiricozzi. SPHINGOLIPIDS AS SIGNALING MOLECULES: THEIR INVOLVEMENT IN HEALTH AND DISEASE.

Degree: 2013, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/217447

► Sphingolipids (SLs) are minor cell membrane amphyphilic components, residing in the external layer of the plasma membrane (PM), with the hydrophobic moiety, the ceramide (Cer),… (more)

▼ Sphingolipids (SLs) are minor cell membrane amphyphilic components, residing in the external layer of the plasma membrane (PM), with the hydrophobic moiety, the ceramide (Cer), inserted into the membrane layer and the hydrophilic head group protruding toward the extracellular environment. They are a family of several compounds with different structural properties: the phospholipid, sphingomyelin (SM), the glycosphingolipids (GSLs) characterized for containing a complex oligosaccharide chain as hydrophilic moiety and gangliosides, GSLs containing sialic acid. As membrane components, SLs participate to modulate several cell processes, such as cell growth, differentiation, morphogenesis, cell to matrix interaction and cell to cell communication. From this, it follows that a defect in SL metabolism can obviously lead to a great number of dysfunctions, ranging from neurodegeneration to cancer. Along my Ph.D. course I considered the different faces of SLs roles: from their involvement in physiology to that in pathology. i.SPHINGOLIPIDS and HEALT. SLs cluster to form SL-enriched domains on cellular PM (lipid rafts, caveolae, and glycosynapses) providing a microenvironment within the PM for reciprocal interaction between lipids and proteins. In particular biochemical analyses have demonstrated that GSLs-enriched microdomains contain several transducer molecules, especially membrane-anchored signal transduction molecules, such as tyrosine kinases belonging to the Src family. Although it has been speculated that GSLs are involved in cell differentiation, proliferation and functions such as phagocytosing, there are quite few evidence that GSLs, by themselves, directly mediate signal transduction, which lead to these cell functions. LACTOSYLCERAMIDE-ENRICHED MICRODOMAIN in NEUTROPHILIS. Lactosylceramide (LacCer), a neutral GSL, is abundantly expressed on human neutrophils, and specifically recognizes several pathogenic microorganisms. It has been previously demonstrated that LacCer forms PM lipid domains, that can be separated by detergent treatment of cells followed by ultracentrifugation, and that these lipid domains are coupled with Lyn, a Src family kinase. Ligand binding to LacCer activates Lyn, resulting in neutrophils functions, such as superoxide generation, phagocytosis and migration. The presence of LacCer molecular species with Cer containing a very long fatty acid chain is necessary for the association of Lyn with LacCer-enriched PM domains and LacCer-mediated functions. Lyn is associated by a palmitoyl anchor to the cytoplasmic leaflet, while LacCer is inserted into the outer layer of membrane bilayer. So the question is: how does LacCer interact with signal transducer molecules? The GSL-protein interactions in neutrophilis have been investigated by photoactivable GSLs. These molecules have been administered and taken up by the cell PM. When cells are illuminated, the photoactivable group, linked to the terminal portion of Cer, yields a very reactive intermediate, that covalently binds the… Advisors/Committee Members: docente guida: S. Sonnino, coordinatore: F. Bonomi, SONNINO, SANDRO, BONOMI, FRANCESCO.

Subjects/Keywords: sphingolipids; Settore BIO/10 - Biochimica

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chiricozzi, E. (2013). SPHINGOLIPIDS AS SIGNALING MOLECULES: THEIR INVOLVEMENT IN HEALTH AND DISEASE. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/217447

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Chiricozzi, E.. “SPHINGOLIPIDS AS SIGNALING MOLECULES: THEIR INVOLVEMENT IN HEALTH AND DISEASE.” 2013. Thesis, Università degli Studi di Milano. Accessed February 28, 2021. http://hdl.handle.net/2434/217447.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Chiricozzi, E.. “SPHINGOLIPIDS AS SIGNALING MOLECULES: THEIR INVOLVEMENT IN HEALTH AND DISEASE.” 2013. Web. 28 Feb 2021.

Vancouver:

Chiricozzi E. SPHINGOLIPIDS AS SIGNALING MOLECULES: THEIR INVOLVEMENT IN HEALTH AND DISEASE. [Internet] [Thesis]. Università degli Studi di Milano; 2013. [cited 2021 Feb 28]. Available from: http://hdl.handle.net/2434/217447.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Chiricozzi E. SPHINGOLIPIDS AS SIGNALING MOLECULES: THEIR INVOLVEMENT IN HEALTH AND DISEASE. [Thesis]. Università degli Studi di Milano; 2013. Available from: http://hdl.handle.net/2434/217447

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Manchester

5. Morris, Thomas. The role of bioactive sphingolipids in vascular calcification.

Degree: PhD, 2016, University of Manchester

URL: https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-bioactive-sphingolipids-in-vascular-calcification(5235985a-0992-432e-9df2-35519725f87a).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.680004

► Vascular calcification is the formation of mineralised tissue within the walls of arteries. The pathology has many similarities to embryonic bone formation and involves the… (more)

▼ Vascular calcification is the formation of mineralised tissue within the walls of arteries. The pathology has many similarities to embryonic bone formation and involves the osteogenic differentiation of vascular smooth muscle cells (VSMCs) and matrix mineralisation. Recent studies have demonstrated that the bioactive sphingolipids, ceramide and sphingosine-1-phosphate (S1P), regulate embryonic bone formation. Ceramide can be generated by lysosomal acid sphingomyelinase (L-SMase) and neutral sphingomyelinase (N-SMase), and be converted to sphingosine by acid ceramidase (ACDase) and subsequently to S1P by sphingosine kinases (SK1 & SK2). This study tested the hypothesis that ceramide and S1P also regulate VSMC matrix mineralisation. VSMCs were cultured in the presence of 3 mM β-glycerophosphate (BGP) to induce osteogenic differentiation and matrix mineralisation. During VSMC mineralisation there were decreases in the activities of L-SMase and N-SMase and increases in the levels of C18 and C20 ceramide. S1P levels also increased during mineralisation as did SK1 and SK2 mRNA and SK activity. These results demonstrate that ceramide and S1P have the potential to regulate VSMC mineralisation. The exogenous addition of C2 ceramide decreased the rate of VSMC matrix mineralisation. Consistent with this, when VSMCs were cultured with 3 mM BGP and the joint L-SMase and ACDase inhibitor, desipramine, total ceramide levels increased and no matrix mineralisation was detected. These findings suggest that ceramide is an inhibitor of VSMCs matrix mineralisation. It was also noted in the presence of 3 mM BGP and desipramine that the mineralisation-associated increase in S1P was inhibited. In agreement with this, when exogenous S1P was added to the VSMCs an increase in matrix mineralisation was observed. Thus, S1P acts as a promoter of matrix mineralisation. To determine how S1P was promoting matrix mineralisation the signalling roles of the ezrin, radixin and moesin (ERM) proteins were investigated. The short-term stimulation of VSMCs with S1P led to the phosphorylation of the ERM proteins and over the mineralisation time-course, when S1P levels increased, the levels of ERM phosphorylation also increased. When VSMCs were cultured in the presence of 3 mM BGP and the inhibitor of ezrin phosphorylation, NSC668394, a decrease in matrix mineralisation was observed. No increases in ERM phosphorylation were seen in the presence of desipramine during the mineralisation time-course Therefore, S1P may be increasing matrix mineralisation through promoting the phosphorylation of the ERM proteins. This work has demonstrated that ceramide inhibits and S1P promotes VSMC matrix mineralisation in vitro. Additionally, this work identifies activation of ERM proteins, downstream of S1P, as a novel signalling pathway promoting matrix mineralisation. Characterisation of novel regulators of VSMC matrix mineralisation in vitro gives insight into the complex mechanisms contributing to vascular calcification in vivo and will aid in identification of novel…

Subjects/Keywords: 616.1; Vascular calcification; Bioactive sphingolipids

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Morris, T. (2016). The role of bioactive sphingolipids in vascular calcification. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-bioactive-sphingolipids-in-vascular-calcification(5235985a-0992-432e-9df2-35519725f87a).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.680004

Chicago Manual of Style (16^th Edition):

Morris, Thomas. “The role of bioactive sphingolipids in vascular calcification.” 2016. Doctoral Dissertation, University of Manchester. Accessed February 28, 2021. https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-bioactive-sphingolipids-in-vascular-calcification(5235985a-0992-432e-9df2-35519725f87a).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.680004.

MLA Handbook (7^th Edition):

Morris, Thomas. “The role of bioactive sphingolipids in vascular calcification.” 2016. Web. 28 Feb 2021.

Vancouver:

Morris T. The role of bioactive sphingolipids in vascular calcification. [Internet] [Doctoral dissertation]. University of Manchester; 2016. [cited 2021 Feb 28]. Available from: https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-bioactive-sphingolipids-in-vascular-calcification(5235985a-0992-432e-9df2-35519725f87a).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.680004.

Council of Science Editors:

Morris T. The role of bioactive sphingolipids in vascular calcification. [Doctoral Dissertation]. University of Manchester; 2016. Available from: https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-bioactive-sphingolipids-in-vascular-calcification(5235985a-0992-432e-9df2-35519725f87a).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.680004

Montana State University

6. Mishra, Pranab K. Synthetic studies toward the preparation of phosphate analogs of sphingolipids.

Degree: PhD, College of Letters & Science, 1997, Montana State University

URL: https://scholarworks.montana.edu/xmlui/handle/1/7914

Subjects/Keywords: Sphingolipids.; Phosphonates.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mishra, P. K. (1997). Synthetic studies toward the preparation of phosphate analogs of sphingolipids. (Doctoral Dissertation). Montana State University. Retrieved from https://scholarworks.montana.edu/xmlui/handle/1/7914

Chicago Manual of Style (16^th Edition):

Mishra, Pranab K. “Synthetic studies toward the preparation of phosphate analogs of sphingolipids.” 1997. Doctoral Dissertation, Montana State University. Accessed February 28, 2021. https://scholarworks.montana.edu/xmlui/handle/1/7914.

MLA Handbook (7^th Edition):

Mishra, Pranab K. “Synthetic studies toward the preparation of phosphate analogs of sphingolipids.” 1997. Web. 28 Feb 2021.

Vancouver:

Mishra PK. Synthetic studies toward the preparation of phosphate analogs of sphingolipids. [Internet] [Doctoral dissertation]. Montana State University; 1997. [cited 2021 Feb 28]. Available from: https://scholarworks.montana.edu/xmlui/handle/1/7914.

Council of Science Editors:

Mishra PK. Synthetic studies toward the preparation of phosphate analogs of sphingolipids. [Doctoral Dissertation]. Montana State University; 1997. Available from: https://scholarworks.montana.edu/xmlui/handle/1/7914

University of Manchester

7. Morris, Thomas. The role of bioactive sphingolipids in vascular calcification.

Degree: 2016, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:294660

► Vascular calcification is the formation of mineralised tissue within the walls of arteries. The pathology has many similarities to embryonic bone formation and involves the… (more)

▼ Vascular calcification is the formation of mineralised tissue within the walls of arteries. The pathology has many similarities to embryonic bone formation and involves the osteogenic differentiation of vascular smooth muscle cells (VSMCs) and matrix mineralisation. Recent studies have demonstrated that the bioactive sphingolipids, ceramide and sphingosine-1-phosphate (S1P), regulate embryonic bone formation. Ceramide can be generated by lysosomal acid sphingomyelinase (L-SMase) and neutral sphingomyelinase (N-SMase), and be converted to sphingosine by acid ceramidase (ACDase) and subsequently to S1P by sphingosine kinases (SK1 & SK2). This study tested the hypothesis that ceramide and S1P also regulate VSMC matrix mineralisation.VSMCs were cultured in the presence of 3 mM β-glycerophosphate (BGP) to induce osteogenic differentiation and matrix mineralisation. During VSMC mineralisation there were decreases in the activities of L-SMase and N-SMase and increases in the levels of C18 and C20 ceramide. S1P levels also increased during mineralisation as did SK1 and SK2 mRNA and SK activity. These results demonstrate that ceramide and S1P have the potential to regulate VSMC mineralisation.The exogenous addition of C2 ceramide decreased the rate of VSMC matrix mineralisation. Consistent with this, when VSMCs were cultured with 3 mM BGP and the joint L-SMase and ACDase inhibitor, desipramine, total ceramide levels increased and no matrix mineralisation was detected. These findings suggest that ceramide is an inhibitor of VSMCs matrix mineralisation. It was also noted in the presence of 3 mM BGP and desipramine that the mineralisation-associated increase in S1P was inhibited. In agreement with this, when exogenous S1P was added to the VSMCs an increase in matrix mineralisation was observed. Thus, S1P acts as a promoter of matrix mineralisation.To determine how S1P was promoting matrix mineralisation the signalling roles of the ezrin, radixin and moesin (ERM) proteins were investigated. The short-term stimulation of VSMCs with S1P led to the phosphorylation of the ERM proteins and over the mineralisation time-course, when S1P levels increased, the levels of ERM phosphorylation also increased. When VSMCs were cultured in the presence of 3 mM BGP and the inhibitor of ezrin phosphorylation, NSC668394, a decrease in matrix mineralisation was observed. No increases in ERM phosphorylation were seen in the presence of desipramine during the mineralisation time-course Therefore, S1P may be increasing matrix mineralisation through promoting the phosphorylation of the ERM proteins.This work has demonstrated that ceramide inhibits and S1P promotes VSMC matrix mineralisation in vitro. Additionally, this work identifies activation of ERM proteins, downstream of S1P, as a novel signalling pathway promoting matrix mineralisation. Characterisation of novel regulators of VSMC matrix mineralisation in vitro gives insight into the complex mechanisms contributing to vascular calcification in vivo and will aid in identification of novel… Advisors/Committee Members: CANFIELD, ANN AE, OHANIAN, VASKEN V, Ohanian, Jacqueline, Canfield, Ann, Ohanian, Vasken.

Subjects/Keywords: Vascular calcification; Bioactive sphingolipids

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Morris, T. (2016). The role of bioactive sphingolipids in vascular calcification. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:294660

Chicago Manual of Style (16^th Edition):

Morris, Thomas. “The role of bioactive sphingolipids in vascular calcification.” 2016. Doctoral Dissertation, University of Manchester. Accessed February 28, 2021. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:294660.

MLA Handbook (7^th Edition):

Morris, Thomas. “The role of bioactive sphingolipids in vascular calcification.” 2016. Web. 28 Feb 2021.

Vancouver:

Morris T. The role of bioactive sphingolipids in vascular calcification. [Internet] [Doctoral dissertation]. University of Manchester; 2016. [cited 2021 Feb 28]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:294660.

Council of Science Editors:

Morris T. The role of bioactive sphingolipids in vascular calcification. [Doctoral Dissertation]. University of Manchester; 2016. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:294660

University of New South Wales

8. Tran, Collin. Investigating the role of dual sphingosine 1-phosphate receptor signalling in neuroprotection.

Degree: Medical Sciences, 2020, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/66567 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:66422/SOURCE02?view=true

► Sphingosine 1-phosphate (S1P) is a signalling lipid that mediates biological processes through five G-protein coupled receptors (S1PR1-5). S1P synthesis occurs through the phosphorylation of sphingosine… (more)

▼ Sphingosine 1-phosphate (S1P) is a signalling lipid that mediates biological processes through five G-protein coupled receptors (S1PR1-5). S1P synthesis occurs through the phosphorylation of sphingosine by sphingosine kinase 1 (SphK1) or SphK2. S1P levels and SphK activity are reduced in multiple neurodegenerative paradigms including Alzheimer’s disease (AD). Pharmacological targeting of S1PRs is neuroprotective in animal models of these diseases. This thesis investigates the cellular and molecular mechanisms behind S1P-mediated neuroprotection. S1P up-regulates four neurotrophic genes (BDNF, PDGFB, HBEGF, and LIF) in primary astrocytes, but not neurons. Induction of these genes is mainly driven by S1PR2 signalling, with minor contributions from S1PR1. Phosphoproteomic analysis showed time-dependent activation of canonical pathways such as the mitogen-activated protein kinase and RhoA pathways, and phosphorylation of cJUN and Yes associated protein (YAP). Immediate early genes (IEGs) were also induced with S1P. Transcription start sites of these neurotrophic factors show predicted binding sites for cJUN and YAP, and the IEGs. While distinct phosphosites were regulated by S1PR1 and S1PR2 signalling, a large subset was regulated by both. However, the RhoA-YAP pathway was exclusively activated by S1PR2. The clinical drug Fingolimod (FTY720) is a sphingosine analogue that is phosphorylated in vivo by SphK2 to form the S1P structural analogue FTY720-P. Previous reports detailing the neuroprotective properties of S1PRs used FTY720-P to investigate the neurotrophic response. Unlike S1P, FTY720-P does not activate the S1PR2-RhoA-YAP pathway in astrocytes. Accordingly, S1P was a much more potent inducer of IEGs and neurotrophic gene expression than FTY720-P. Additionally, S1P but not FTY720-P significantly attenuated excitotoxic neuronal cell death in vitro when co-cultured with glia. Neuroprotection was ablated upon incubation with a LIF neutralising antibody, but not with antagonists to BDNF or HBEGF signalling. I have therefore established a novel neuroprotective pathway in which S1P stimulates secretion of the growth factor LIF by astrocytes, which protects neurons against excitotoxic cell death. This pathway requires dual S1PR1 and S1PR2 signalling in astrocytes, thus explaining the inefficacy of FTY720-P. Current S1PR therapies do not target S1PR2 and targeting this receptor may be a novel therapeutic option for AD and other neurodegenerative conditions. Advisors/Committee Members: Carrive, Pascal, Medical Sciences, Faculty of Medicine, UNSW, Don, Anthony, University of Sydney.

Subjects/Keywords: GPCR; Sphingolipids; Alzheimer's disease

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tran, C. (2020). Investigating the role of dual sphingosine 1-phosphate receptor signalling in neuroprotection. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/66567 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:66422/SOURCE02?view=true

Chicago Manual of Style (16^th Edition):

Tran, Collin. “Investigating the role of dual sphingosine 1-phosphate receptor signalling in neuroprotection.” 2020. Doctoral Dissertation, University of New South Wales. Accessed February 28, 2021. http://handle.unsw.edu.au/1959.4/66567 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:66422/SOURCE02?view=true.

MLA Handbook (7^th Edition):

Tran, Collin. “Investigating the role of dual sphingosine 1-phosphate receptor signalling in neuroprotection.” 2020. Web. 28 Feb 2021.

Vancouver:

Tran C. Investigating the role of dual sphingosine 1-phosphate receptor signalling in neuroprotection. [Internet] [Doctoral dissertation]. University of New South Wales; 2020. [cited 2021 Feb 28]. Available from: http://handle.unsw.edu.au/1959.4/66567 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:66422/SOURCE02?view=true.

Council of Science Editors:

Tran C. Investigating the role of dual sphingosine 1-phosphate receptor signalling in neuroprotection. [Doctoral Dissertation]. University of New South Wales; 2020. Available from: http://handle.unsw.edu.au/1959.4/66567 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:66422/SOURCE02?view=true

9. Niemelä, Perttu. Computational Modelling of Lipid Bilayers with Sphingomyelin and Sterols.

Degree: 2007, Helsinki University of Technology

URL: http://lib.tkk.fi/Diss/2007/isbn9789521037139/

►

This thesis is based on atom-scale molecular dynamics simulations on lipid bilayers. The study concentrates on structural and dynamic properties of lipid bilayers, involving three… (more)

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This thesis is based on atom-scale molecular dynamics simulations on lipid bilayers. The study concentrates on structural and dynamic properties of lipid bilayers, involving three lipid classes that are the main constituents of, for example, eukaryotic plasma membranes: phosphatidylcholines (PCs), sphingomyelins (SMs) and sterols. The discussion in the thesis starts from the simplest bilayers that are comprised of single lipid components, and gradually moves towards more complex systems, approaching a better description of biological membranes. Studies on single-component bilayers concentrate on the properties of SM. In a comparison with a structurally similar PC, it is shown that the packing of SM in a bilayer is more compact and that the lipids are more ordered than in a PC bilayer. Additionally, unsaturation increases the fluidity of SM bilayer less than typically in PC bilayers. The above differences in the bilayer properties of SM and PC are explained by detailed analysis of the intra- and intermolecular hydrogen bonding in the SM bilayer. The results on the effects of chain length on SM bilayers are mainly involved with the bilayer thickness and the interdigitation of the longer chains through the bilayer centre. The studies on sterols involves two parts. First, the molecular interactions of cholesterol (CHOL) with PC and SM lipids are characterised in detail. In particular, the aim is to reveal aspects of the SM-CHOL interaction, which has been proposed to be a key factor in the formation of lateral domains called lipid rafts in biological membranes. Second, the properties of bilayers with binary mixtures of PC and different sterols are discussed. It is shown that the acyl chain order in the studied systems is correlated with the tilt of the sterol. Also, we find that CHOL is superior among the studied sterols in ordering the acyl chains. The studies on lipid raft bilayers involve three component mixtures of PC, SM, and CHOL. Large-scale simulations of two types of lipid environments are compared: raft-like membranes, which are high in SM and CHOL concentration, and non-raft membranes, which comprise of mostly PC. The results reveal that the raft-like membranes are much more rigid, ordered and packed, but also characterised by slower dynamics of the lipids, when compared to the non-raft environment. In the discussion, we show that the different properties of the two membrane environments may have significant implications on the functioning and partitioning of membrane proteins. In particular, the observed differences in the lateral pressure profiles are suggested to alter the open-state probability of an ion channel MscL.

Internal report / Helsinki Institute of Physics, ISSN 1455-0563; 2007-03

Advisors/Committee Members: Helsinki University of Technology, Department of Engineering Physics and Mathematics, Laboratory of Physics, Helsinki Institute of Physics.

Subjects/Keywords: molecular dynamics; lipid rafts; cholesterol; sphingolipids

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Niemelä, P. (2007). Computational Modelling of Lipid Bilayers with Sphingomyelin and Sterols. (Thesis). Helsinki University of Technology. Retrieved from http://lib.tkk.fi/Diss/2007/isbn9789521037139/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Niemelä, Perttu. “Computational Modelling of Lipid Bilayers with Sphingomyelin and Sterols.” 2007. Thesis, Helsinki University of Technology. Accessed February 28, 2021. http://lib.tkk.fi/Diss/2007/isbn9789521037139/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Niemelä, Perttu. “Computational Modelling of Lipid Bilayers with Sphingomyelin and Sterols.” 2007. Web. 28 Feb 2021.

Vancouver:

Niemelä P. Computational Modelling of Lipid Bilayers with Sphingomyelin and Sterols. [Internet] [Thesis]. Helsinki University of Technology; 2007. [cited 2021 Feb 28]. Available from: http://lib.tkk.fi/Diss/2007/isbn9789521037139/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Niemelä P. Computational Modelling of Lipid Bilayers with Sphingomyelin and Sterols. [Thesis]. Helsinki University of Technology; 2007. Available from: http://lib.tkk.fi/Diss/2007/isbn9789521037139/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

10. José Márcio Pimentel Martins. Avaliação do biomarcador (esfinganina / esfingosina) na intoxicação por fumonisinas em suínos.

Degree: 2005, Universidade Federal Rural do Rio de Janeiro

URL: http://bdtd.ufrrj.br//tde_busca/arquivo.php?codArquivo=841

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Fumonisinas são m grupo de micotoxinas produzidas por espécies do gênero Fusarium, fungo de ampla distribuição mundial e com alta prevalência em grãos, principalmente no… (more)

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Fumonisinas são m grupo de micotoxinas produzidas por espécies do gênero Fusarium, fungo de ampla distribuição mundial e com alta prevalência em grãos, principalmente no milho, que freqüentemente veiculam estas toxinas para subprodutos ou para alimentos destinados ao consumo humano e animal. As fumonisinas são inibidores específicos da síntese dos esfingolipídios, causando acúmulos de esfinganina (Sa) e esfingosina (So) nas células. A proporção entre Sa e So tem sido relatada como sendo eficaz biomarcador de intoxicação por fumonisinas em animais e humanos, podendo ser utilizada em levantamentos epidemiológicos sobre a exposição de uma determinada população às fumonisinas. Nos eqüídeos causam leucoencefalomalácia eqüina (LEME), edema pulmonar e hidrotórax em suínos, hepatotoxidez, hepatocarcinogenicidade e nefropatias em ratos, aves e coelhos, além de diversos efeitos no sistema imune. O principal ingrediente das rações utilizadas para suínos é o milho e seus derivados e por isso a pesquisa de micotoxinas, em especial fumonisinas nas rações utilizadas em suinoculturas é de vital importância devido às perdas econômicas acarretadas. Foram utilizadas amostras de sangue e urina de quatro granjas fornecedoras de um abatedouro de suínos, localizado no município do Rio de Janeiro. As amostras de sangue foram obtidas durante a sangria e as de urina por punção vesical, no momento da evisceração.Todas mantidas sob refrigeração e congelamento até a análise. O número de amostras coletadas foi referente a 10 % dos animais abatidos de cada propriedade / dia, perfazendo o total de 76 amostras, durante 60 dias. Para determinação de esfingolipídios foram utilizados os métodos propostos por CASTEGNARO et al. (1996, 1998), para análise por cromatografia líquida de alta eficiência. Os resultados demonstraram que 17,77 % das amostras de soro tinham o perfil típico de intoxicação para fumonisinas, em 11,11 % apresentaram perfil sugestivo da influência de aflatoxinas. Em uma das propriedades 100 % dos animais avaliados apresentaram alterações típicas da ação das fumonisinas. Nas amostras de urina, 26 % indicaram a ação típica das fumonisinas e em 39,13 % as alterações indicaram a influência das aflatoxinas além das fumonisinas. A utilização deste biomarcador em condições naturais mostrou-se eficaz na detecção da exposição às fumonisinas, porém deve-se considerar o comportamento tanto da So quanto de Sa, que permitem uma avaliação mais abrangente.

Fumonisins are a group of mycotoxins produced by species of the gender Fusarium, fungi of world wide distribution and with high prevalence in grains, mainly in corn, that frequently transmit these toxins to by-products or to foods destined to the human and animal consumption. The fumonisins are specific inhibitors of the synthesis of sphingolipids, causing sphinganine (Sa) and sphingosine (So) accumulations in the cells. The proportion among Sa and So has been told as being an effective intoxication biomarker for fumonisins in animals and humans. Could be used as a biomarker, in epidemic…

Advisors/Committee Members: Glória Maria Direito.

Subjects/Keywords: Fusarium; suínos; esfingolipídios.; MEDICINA VETERINARIA; swine; sphingolipids.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Martins, J. M. P. (2005). Avaliação do biomarcador (esfinganina / esfingosina) na intoxicação por fumonisinas em suínos. (Thesis). Universidade Federal Rural do Rio de Janeiro. Retrieved from http://bdtd.ufrrj.br//tde_busca/arquivo.php?codArquivo=841

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Martins, José Márcio Pimentel. “Avaliação do biomarcador (esfinganina / esfingosina) na intoxicação por fumonisinas em suínos.” 2005. Thesis, Universidade Federal Rural do Rio de Janeiro. Accessed February 28, 2021. http://bdtd.ufrrj.br//tde_busca/arquivo.php?codArquivo=841.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Martins, José Márcio Pimentel. “Avaliação do biomarcador (esfinganina / esfingosina) na intoxicação por fumonisinas em suínos.” 2005. Web. 28 Feb 2021.

Vancouver:

Martins JMP. Avaliação do biomarcador (esfinganina / esfingosina) na intoxicação por fumonisinas em suínos. [Internet] [Thesis]. Universidade Federal Rural do Rio de Janeiro; 2005. [cited 2021 Feb 28]. Available from: http://bdtd.ufrrj.br//tde_busca/arquivo.php?codArquivo=841.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Martins JMP. Avaliação do biomarcador (esfinganina / esfingosina) na intoxicação por fumonisinas em suínos. [Thesis]. Universidade Federal Rural do Rio de Janeiro; 2005. Available from: http://bdtd.ufrrj.br//tde_busca/arquivo.php?codArquivo=841

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Edinburgh

11. Beattie, Ashley Emily. Mechanistic studies of the pyridoxal 5'-phosphate-dependent enzyme serine palmitoyltransferase : substrates, cofactor and inhibitors.

Degree: PhD, 2014, University of Edinburgh

URL: http://hdl.handle.net/1842/10059

► Sphingolipids (SL) are essential structural components of membranes found in all eukaryotes and have also been identified in some bacteria. The first step of the… (more)

▼ Sphingolipids (SL) are essential structural components of membranes found in all eukaryotes and have also been identified in some bacteria. The first step of the SL biosynthetic pathway across all species is catalysed by serine palmitoyltransferase (SPT), a member of the alpha-oxoamine synthase (AOS) family of pyridoxal 5’- phosphate (PLP)-dependent enzymes. AOS enzymes are involved in the biosynthesis of a range of important natural products such as heme, vitamins and antibiotics where they catalyse the reaction between amino acid and acyl-thioester substrates. Substrate specificity across the family is of great importance, as human mutant SPTs shift the substrate specificity from L-serine to glycine or L-alanine that lead to production of deoxy-sphingolipids that are toxic to mammalian cells. PLP, a form of vitamin B6, is one of nature’s most versatile catalysts and is involved in over 160 enzymes that carry out diverse reactions on amine-containing substrates. This work probes the functional role of the phosphate group of PLP, usually housed in a phosphate binding cup (PBC) and investigates the need for a novel and unexpected H-bond between the hydroxyl group of the L-serine substrate and the 5’-phosphate group of PLP in SPT. In this study, the PLP cofactor was removed from SPT with amino-thiol substrates which act as mechanism-based inhibitors of SPT via production of a thiazolidine adduct. Replacement of natural PLP with the dephosphorylated form of the cofactor, pyridoxal, allowed a study on the importance of the PLP phosphate:L-serine H-bond on substrate specificity and optimal SPT activity. Furthermore, analysis of the phosphate binding cup of the ALAS:PLP:glycine external aldimine, a related AOS family member; revealed an important residue that could possibly be involved in determining substrate specificity of different members of the AOS family. PBC analysis also expanded, with a detailed and interesting study of a novel SPT:PLP:myriocin inhibitor complex. Human SPT is a heterodimeric, membrane-bound enzyme composed of two subunits (hLCB1/hLCB2) which is thought to contain a single PLP-containing active site. Mutations in human hLCB1 have been linked to the rare sphingolipid metabolic disease hereditary sensory neuropathy I (HSAN1). Recent studies identified three heterozygous missense mutations in the second human SPT subunit hLCB2 that show a significant loss in SPT activity. The three human SPT mutations V359M, G385V and I504F were mapped onto the bacterial S. paucimobilis SPT as V246M, G268V and G385F. These bacterial SPT mutant mimics reveal that the amino acid changes have varying impacts; they perturb the PLP cofactor binding, reduce the affinity for both substrates, decrease the enzyme activity, and, in the most severe case, cause the protein to be expressed in an insoluble form. SPTs and most of the other members of the AOS family utilise an acyl-CoA thioester substrate. In contrast, a sphingolipid-producing bacterium, S. wittichii, is thought to use a small type II acyl carrier protein (ACP) to…

Subjects/Keywords: 572; sphingolipids; AOS enzymes; PLP; SPT

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Beattie, A. E. (2014). Mechanistic studies of the pyridoxal 5'-phosphate-dependent enzyme serine palmitoyltransferase : substrates, cofactor and inhibitors. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/10059

Chicago Manual of Style (16^th Edition):

Beattie, Ashley Emily. “Mechanistic studies of the pyridoxal 5'-phosphate-dependent enzyme serine palmitoyltransferase : substrates, cofactor and inhibitors.” 2014. Doctoral Dissertation, University of Edinburgh. Accessed February 28, 2021. http://hdl.handle.net/1842/10059.

MLA Handbook (7^th Edition):

Beattie, Ashley Emily. “Mechanistic studies of the pyridoxal 5'-phosphate-dependent enzyme serine palmitoyltransferase : substrates, cofactor and inhibitors.” 2014. Web. 28 Feb 2021.

Vancouver:

Beattie AE. Mechanistic studies of the pyridoxal 5'-phosphate-dependent enzyme serine palmitoyltransferase : substrates, cofactor and inhibitors. [Internet] [Doctoral dissertation]. University of Edinburgh; 2014. [cited 2021 Feb 28]. Available from: http://hdl.handle.net/1842/10059.

Council of Science Editors:

Beattie AE. Mechanistic studies of the pyridoxal 5'-phosphate-dependent enzyme serine palmitoyltransferase : substrates, cofactor and inhibitors. [Doctoral Dissertation]. University of Edinburgh; 2014. Available from: http://hdl.handle.net/1842/10059

University of Washington

12. Conner, Emily L. Diet Quality and Circulating Sphingolipids: The Strong Heart Family Study.

Degree: 2018, University of Washington

URL: http://hdl.handle.net/1773/43117

► Sphingolipids, including ceramides (Cer) and sphingomyelins (SM), are involved in the development of chronic disease through stress response, inflammation, insulin sensitivity, and more. Plasma sphingolipids… (more)

Subjects/Keywords: Diet Quality; Sphingolipids; Nutrition; Nutritional sciences

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Conner, E. L. (2018). Diet Quality and Circulating Sphingolipids: The Strong Heart Family Study. (Thesis). University of Washington. Retrieved from http://hdl.handle.net/1773/43117

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Conner, Emily L. “Diet Quality and Circulating Sphingolipids: The Strong Heart Family Study.” 2018. Thesis, University of Washington. Accessed February 28, 2021. http://hdl.handle.net/1773/43117.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Conner, Emily L. “Diet Quality and Circulating Sphingolipids: The Strong Heart Family Study.” 2018. Web. 28 Feb 2021.

Vancouver:

Conner EL. Diet Quality and Circulating Sphingolipids: The Strong Heart Family Study. [Internet] [Thesis]. University of Washington; 2018. [cited 2021 Feb 28]. Available from: http://hdl.handle.net/1773/43117.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Conner EL. Diet Quality and Circulating Sphingolipids: The Strong Heart Family Study. [Thesis]. University of Washington; 2018. Available from: http://hdl.handle.net/1773/43117

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Delft University of Technology

13. Lisman, Q. The Golgi: A transition point in membrane lipid composition and topology.

Degree: 2004, Delft University of Technology

URL: http://resolver.tudelft.nl/uuid:813eea2e-cf1c-44f0-8b19-9bef56741c0a ; urn:NBN:nl:ui:24-uuid:813eea2e-cf1c-44f0-8b19-9bef56741c0a ; urn:NBN:nl:ui:24-uuid:813eea2e-cf1c-44f0-8b19-9bef56741c0a ; http://resolver.tudelft.nl/uuid:813eea2e-cf1c-44f0-8b19-9bef56741c0a

► The exciting developments in the fields of sphingolipid-mediated signal transduction and sphingolipid-mediated protein sorting have led to a tremendous activity in the studies of sphingolipid… (more)

Subjects/Keywords: Golgi; yeast; sphingolipids

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APA (6^th Edition):

Lisman, Q. (2004). The Golgi: A transition point in membrane lipid composition and topology. (Doctoral Dissertation). Delft University of Technology. Retrieved from http://resolver.tudelft.nl/uuid:813eea2e-cf1c-44f0-8b19-9bef56741c0a ; urn:NBN:nl:ui:24-uuid:813eea2e-cf1c-44f0-8b19-9bef56741c0a ; urn:NBN:nl:ui:24-uuid:813eea2e-cf1c-44f0-8b19-9bef56741c0a ; http://resolver.tudelft.nl/uuid:813eea2e-cf1c-44f0-8b19-9bef56741c0a

Chicago Manual of Style (16^th Edition):

Lisman, Q. “The Golgi: A transition point in membrane lipid composition and topology.” 2004. Doctoral Dissertation, Delft University of Technology. Accessed February 28, 2021. http://resolver.tudelft.nl/uuid:813eea2e-cf1c-44f0-8b19-9bef56741c0a ; urn:NBN:nl:ui:24-uuid:813eea2e-cf1c-44f0-8b19-9bef56741c0a ; urn:NBN:nl:ui:24-uuid:813eea2e-cf1c-44f0-8b19-9bef56741c0a ; http://resolver.tudelft.nl/uuid:813eea2e-cf1c-44f0-8b19-9bef56741c0a.

MLA Handbook (7^th Edition):

Lisman, Q. “The Golgi: A transition point in membrane lipid composition and topology.” 2004. Web. 28 Feb 2021.

Vancouver:

Lisman Q. The Golgi: A transition point in membrane lipid composition and topology. [Internet] [Doctoral dissertation]. Delft University of Technology; 2004. [cited 2021 Feb 28]. Available from: http://resolver.tudelft.nl/uuid:813eea2e-cf1c-44f0-8b19-9bef56741c0a ; urn:NBN:nl:ui:24-uuid:813eea2e-cf1c-44f0-8b19-9bef56741c0a ; urn:NBN:nl:ui:24-uuid:813eea2e-cf1c-44f0-8b19-9bef56741c0a ; http://resolver.tudelft.nl/uuid:813eea2e-cf1c-44f0-8b19-9bef56741c0a.

Council of Science Editors:

Lisman Q. The Golgi: A transition point in membrane lipid composition and topology. [Doctoral Dissertation]. Delft University of Technology; 2004. Available from: http://resolver.tudelft.nl/uuid:813eea2e-cf1c-44f0-8b19-9bef56741c0a ; urn:NBN:nl:ui:24-uuid:813eea2e-cf1c-44f0-8b19-9bef56741c0a ; urn:NBN:nl:ui:24-uuid:813eea2e-cf1c-44f0-8b19-9bef56741c0a ; http://resolver.tudelft.nl/uuid:813eea2e-cf1c-44f0-8b19-9bef56741c0a

University of Toronto

14. Szelag, Katherine Jane. Role of Acid Sphingomyelinase in Murine Placentation.

Degree: 2018, University of Toronto

URL: http://hdl.handle.net/1807/102822

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Growing evidence has implicated bioactive sphingolipids and their associated enzymes in proper placentation. Previous experiments done in our lab have showed compromised placental development and… (more)

Subjects/Keywords: Acid Sphingomyelinase; Murine Placenta; Placentation; Sphingolipids; 0758

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Szelag, K. J. (2018). Role of Acid Sphingomyelinase in Murine Placentation. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/102822

Chicago Manual of Style (16^th Edition):

Szelag, Katherine Jane. “Role of Acid Sphingomyelinase in Murine Placentation.” 2018. Masters Thesis, University of Toronto. Accessed February 28, 2021. http://hdl.handle.net/1807/102822.

MLA Handbook (7^th Edition):

Szelag, Katherine Jane. “Role of Acid Sphingomyelinase in Murine Placentation.” 2018. Web. 28 Feb 2021.

Vancouver:

Szelag KJ. Role of Acid Sphingomyelinase in Murine Placentation. [Internet] [Masters thesis]. University of Toronto; 2018. [cited 2021 Feb 28]. Available from: http://hdl.handle.net/1807/102822.

Council of Science Editors:

Szelag KJ. Role of Acid Sphingomyelinase in Murine Placentation. [Masters Thesis]. University of Toronto; 2018. Available from: http://hdl.handle.net/1807/102822

Michigan State University

15. Krisnangkura, Kanit, 1943-. Studies on the biosynthesis of sphingolipid bases.

Degree: PhD, Department of Biochemistry, 1974, Michigan State University

URL: http://etd.lib.msu.edu/islandora/object/etd:34981

Subjects/Keywords: Sphingolipids; Lipids – Synthesis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Krisnangkura, Kanit, 1. (1974). Studies on the biosynthesis of sphingolipid bases. (Doctoral Dissertation). Michigan State University. Retrieved from http://etd.lib.msu.edu/islandora/object/etd:34981

Chicago Manual of Style (16^th Edition):

Krisnangkura, Kanit, 1943-. “Studies on the biosynthesis of sphingolipid bases.” 1974. Doctoral Dissertation, Michigan State University. Accessed February 28, 2021. http://etd.lib.msu.edu/islandora/object/etd:34981.

MLA Handbook (7^th Edition):

Krisnangkura, Kanit, 1943-. “Studies on the biosynthesis of sphingolipid bases.” 1974. Web. 28 Feb 2021.

Vancouver:

Krisnangkura, Kanit 1. Studies on the biosynthesis of sphingolipid bases. [Internet] [Doctoral dissertation]. Michigan State University; 1974. [cited 2021 Feb 28]. Available from: http://etd.lib.msu.edu/islandora/object/etd:34981.

Council of Science Editors:

Krisnangkura, Kanit 1. Studies on the biosynthesis of sphingolipid bases. [Doctoral Dissertation]. Michigan State University; 1974. Available from: http://etd.lib.msu.edu/islandora/object/etd:34981

University of Illinois – Urbana-Champaign

16. Kim, Raehyun. Investigating sphingolipid behavior and function using metabolic labeling.

Degree: PhD, Chemical Engineering, 2016, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/93059

► The past few decades of research have accumulated a body of evidence that membrane lipids are far more than merely the structural components of biological… (more)

▼ The past few decades of research have accumulated a body of evidence that membrane lipids are far more than merely the structural components of biological membranes. Instead, membrane lipids play important roles in cellular functions in multiple ways. Sphingolipids are a group of lipids that are involved in various cellular processes that are crucial for cell survival and proliferation. However, our understanding of sphingolipid function is limited due to the complexity of their behaviors and the lack of proper tools to address and decipher this complexity. Chapters 2 and 3 present metabolic labeling with fluorophores and stable isotope tags, respectively, as tools to investigate sphingolipid behaviors. Metabolic labeling enables one to detect and directly observe sphingolipids, and not the activities or levels of the enzymes that metabolize them. Metabolic labeling of cells with fluorescent sphingosines enabled visualization of the sphingosine metabolites in live cells and also showed potential for studies of metabolism and in vitro assays. Use of stable isotope tagged sphingolipid precursors, in conjunction with LC-MS/MS analysis, provided a more comprehensive and complete dataset than traditional radiolabeling, including information about unlabeled as well as labeled species. These tools offer great opportunities to explore sphingolipid behaviors. In Chapter 4, based on the observations that sphingolipids have significant roles in membrane organization and that virus infection requires intense membrane reorganization, the involvement of acid sphingomyelinase or sphingomyelin phosphodiesterase 1 (SMPD1), a sphingolipid metabolizing enzyme, in influenza virus infection and particularly its entry was evaluated using RNAi and a pharmacological inhibitor. Western blotting performed prior to infection showed that a significantly higher level of SMPD1 was present in the medium than in the cells. Lowering SMPD1 levels by RNAi or a functional pharmacologic inhibitor, desipramine, did not cause a statistically meaningful change in influenza virus entry. However, influenza virus infection itself was correlated with upregulated SMPD1 levels at the early phase of infection, opening the possibility that sphingolipids may still play an important role in influenza virus infection. Further investigation of the role of SMPD1 in influenza virus infection is necessary. Lastly, in Chapter 5, the cellular uptake of protein-coated nanoparticles was investigated in an effort to understand how plasma proteins interact with the nanoparticle surface, and to enhance the efficiency of targeted nanoparticle delivery with an in vitro system that mimics the in vivo environment. Formation of the protein corona, the protein layer that adsorbs on the surface of the nanoparticle when it is exposed to a biological fluid, is reported to prevent the desired interactions between the nanoparticles and the target cells. Exploiting the well-established mechanism of opsonin-mediated endocytosis in immune cells, we tested whether the protein corona… Advisors/Committee Members: Kraft, Mary L (advisor), Kraft, Mary L (Committee Chair), Bailey, Ryan C (committee member), Leckband, Deborah E (committee member), Schroeder, Charles M (committee member).

Subjects/Keywords: Sphingolipids; Lipids; Isotope labeling; Metabolic labeling

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kim, R. (2016). Investigating sphingolipid behavior and function using metabolic labeling. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/93059

Chicago Manual of Style (16^th Edition):

Kim, Raehyun. “Investigating sphingolipid behavior and function using metabolic labeling.” 2016. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed February 28, 2021. http://hdl.handle.net/2142/93059.

MLA Handbook (7^th Edition):

Kim, Raehyun. “Investigating sphingolipid behavior and function using metabolic labeling.” 2016. Web. 28 Feb 2021.

Vancouver:

Kim R. Investigating sphingolipid behavior and function using metabolic labeling. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2016. [cited 2021 Feb 28]. Available from: http://hdl.handle.net/2142/93059.

Council of Science Editors:

Kim R. Investigating sphingolipid behavior and function using metabolic labeling. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2016. Available from: http://hdl.handle.net/2142/93059

University of Aberdeen

17. McDowell, Alix-Marie. The role of cyclooxygenase and sphingolipids in angiogenesis.

Degree: Institute of Medical Sciences., 2010, University of Aberdeen

URL: http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=203840 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=203840&custom_att_2=simple_viewer

Subjects/Keywords: Neovascularization.; Cyclooxygenases.; Sphingolipids.

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APA (6^th Edition):

McDowell, A. (2010). The role of cyclooxygenase and sphingolipids in angiogenesis. (Doctoral Dissertation). University of Aberdeen. Retrieved from http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=203840 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=203840&custom_att_2=simple_viewer

Chicago Manual of Style (16^th Edition):

McDowell, Alix-Marie. “The role of cyclooxygenase and sphingolipids in angiogenesis.” 2010. Doctoral Dissertation, University of Aberdeen. Accessed February 28, 2021. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=203840 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=203840&custom_att_2=simple_viewer.

MLA Handbook (7^th Edition):

McDowell, Alix-Marie. “The role of cyclooxygenase and sphingolipids in angiogenesis.” 2010. Web. 28 Feb 2021.

Vancouver:

McDowell A. The role of cyclooxygenase and sphingolipids in angiogenesis. [Internet] [Doctoral dissertation]. University of Aberdeen; 2010. [cited 2021 Feb 28]. Available from: http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=203840 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=203840&custom_att_2=simple_viewer.

Council of Science Editors:

McDowell A. The role of cyclooxygenase and sphingolipids in angiogenesis. [Doctoral Dissertation]. University of Aberdeen; 2010. Available from: http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=203840 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=203840&custom_att_2=simple_viewer

Duquesne University

18. Surlow, Beth A. The Role of the B-Type Phospholipases in S. cerevisiae: Function, Regulation, and Physiological Relevance in Lipid Homeostasis.

Degree: PhD, Biological Sciences, 2014, Duquesne University

URL: https://dsc.duq.edu/etd/1255

► Membrane phospholipid synthesis and turnover is a continual process during normal cell growth. The turnover of the glycerophospholipids by B-type phospholipases (PLBs) in Saccharomyces cerevisiae… (more)

Subjects/Keywords: Glycerophosphocholine; Phospholipases; Phospholipids; Protein Kinase; Sphingolipids; Yeast

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APA (6^th Edition):

Surlow, B. A. (2014). The Role of the B-Type Phospholipases in S. cerevisiae: Function, Regulation, and Physiological Relevance in Lipid Homeostasis. (Doctoral Dissertation). Duquesne University. Retrieved from https://dsc.duq.edu/etd/1255

Chicago Manual of Style (16^th Edition):

Surlow, Beth A. “The Role of the B-Type Phospholipases in S. cerevisiae: Function, Regulation, and Physiological Relevance in Lipid Homeostasis.” 2014. Doctoral Dissertation, Duquesne University. Accessed February 28, 2021. https://dsc.duq.edu/etd/1255.

MLA Handbook (7^th Edition):

Surlow, Beth A. “The Role of the B-Type Phospholipases in S. cerevisiae: Function, Regulation, and Physiological Relevance in Lipid Homeostasis.” 2014. Web. 28 Feb 2021.

Vancouver:

Surlow BA. The Role of the B-Type Phospholipases in S. cerevisiae: Function, Regulation, and Physiological Relevance in Lipid Homeostasis. [Internet] [Doctoral dissertation]. Duquesne University; 2014. [cited 2021 Feb 28]. Available from: https://dsc.duq.edu/etd/1255.

Council of Science Editors:

Surlow BA. The Role of the B-Type Phospholipases in S. cerevisiae: Function, Regulation, and Physiological Relevance in Lipid Homeostasis. [Doctoral Dissertation]. Duquesne University; 2014. Available from: https://dsc.duq.edu/etd/1255

Georgia Tech

19. Kollmeyer, Jessica Elaine. Regulation of Galactosylceramide Biosynthesis.

Degree: MS, Biology, 2006, Georgia Tech

URL: http://hdl.handle.net/1853/11630

► An important branchpoint of mammalian sphingolipid metabolism occurs at the step where ceramides are glycosylated to glucosylceramide (GlcCer) versus galactosylceramide (GalCer), which are precursors of… (more)

Subjects/Keywords: Galacotsylceramide; Glycosphingolipids; Sphingolipids

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APA (6^th Edition):

Kollmeyer, J. E. (2006). Regulation of Galactosylceramide Biosynthesis. (Masters Thesis). Georgia Tech. Retrieved from http://hdl.handle.net/1853/11630

Chicago Manual of Style (16^th Edition):

Kollmeyer, Jessica Elaine. “Regulation of Galactosylceramide Biosynthesis.” 2006. Masters Thesis, Georgia Tech. Accessed February 28, 2021. http://hdl.handle.net/1853/11630.

MLA Handbook (7^th Edition):

Kollmeyer, Jessica Elaine. “Regulation of Galactosylceramide Biosynthesis.” 2006. Web. 28 Feb 2021.

Vancouver:

Kollmeyer JE. Regulation of Galactosylceramide Biosynthesis. [Internet] [Masters thesis]. Georgia Tech; 2006. [cited 2021 Feb 28]. Available from: http://hdl.handle.net/1853/11630.

Council of Science Editors:

Kollmeyer JE. Regulation of Galactosylceramide Biosynthesis. [Masters Thesis]. Georgia Tech; 2006. Available from: http://hdl.handle.net/1853/11630

Michigan State University

20. Chakravarthy, Harshini. The role of altered sphingolipid metabolism in the development of diabetic retinopathy.

Degree: 2015, Michigan State University

URL: http://etd.lib.msu.edu/islandora/object/etd:3586

►

Thesis Ph. D. Michigan State University. Physiology 2015.

Diabetic retinopathy (DR) is a vision-threatening microvascular complication of diabetes mellitus, and around 67% of patients have… (more)

▼

Thesis Ph. D. Michigan State University. Physiology 2015.

Diabetic retinopathy (DR) is a vision-threatening microvascular complication of diabetes mellitus, and around 67% of patients have some degree of retinopathy after ten years of diabetes [1]. In spite of decades of investigations, the precise molecular mechanisms involved in the pathogenesis of DR have not been completely deciphered. The main aim of this dissertation is to provide an important molecular link connecting diabetic dyslipidemia with retinal vascular degeneration associated with diabetes. Our studies reveal a central pathway of sphingolipid metabolism involved in the development of DR, concurrently affecting function of bone marrow (BM)-derived inflammatory cells contributing to retinal inflammation and microvascular injury, and negatively affecting repair of retinal vasculature by BM-derived circulating angiogenic cells (CAC). Notably, we reveal that normalizing the pro-inflammatory and reparative functions of these BM-derived cells by modulating their lipid metabolism improves the outcomes of DR.First, we explored the link between bone marrow and DR using a mouse model of diabetes, stably engrafted with GFP+ bone marrow. We demonstrated that diabetes has a significant long-term effect on the BM-derived inflammatory monocytes as well as reparative circulating angiogenic cells (CAC) that circulate in the blood, localize to the retina and undergo further differentiation. Our findings indicate that BM-derived cells could play a central role in the development of DR. Secondly, we investigated the role of altered sphingolipid metabolism in DR. We addressed the hypothesis that perturbation of a specific sphingolipid pathway in BM-derived cells may contribute to inflammation and vascular damage in the diabetic retina. We demonstrated that activation of an essential enzyme of sphingolipid metabolism, acid sphingomyelinase (ASM) in BM-derived cells plays a crucial role in retinal microvascular deterioration associated with diabetes. Inhibition of ASM in the diabetic BM prevented activation of BM-derived microglia-like cells and normalized retinal levels of proinflammatory cytokines. Notably, ASM also caused accumulation of ceramide on cell membrane of BM-derived reparative CACs, thereby reducing membrane fluidity and impairing CAC migration. Inhibition of ASM in these reparative cells improved membrane fluidity and homing of these cells to damaged retinal vessels in a mouse model of DR.Finally, to demonstrate the effect of diabetes on the in vivo homing ability of CACs, we injected purified GFP-expressing CACs into the vitreous of healthy mice. We observed that increased numbers of diabetic CACs remained trapped in the retina without returning to their BM niche, implying impaired migration and homing efficiency of the diabetic CACs. However, inhibition of ASM in diabetic CACs improved their clearance from retina and homing into the BM niche, demonstrating that ASM upregulation in diabetes contributes to impaired migration and homing of reparative…

Advisors/Committee Members: Busik, Julia V, Esselman, Walter, Parameswaran, Narayanan, Mohr, Susanne, Reid, Gavin.

Subjects/Keywords: Diabetic retinopathy – Etiology; Sphingolipids – Metabolism; Physiology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chakravarthy, H. (2015). The role of altered sphingolipid metabolism in the development of diabetic retinopathy. (Thesis). Michigan State University. Retrieved from http://etd.lib.msu.edu/islandora/object/etd:3586

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Chakravarthy, Harshini. “The role of altered sphingolipid metabolism in the development of diabetic retinopathy.” 2015. Thesis, Michigan State University. Accessed February 28, 2021. http://etd.lib.msu.edu/islandora/object/etd:3586.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Chakravarthy, Harshini. “The role of altered sphingolipid metabolism in the development of diabetic retinopathy.” 2015. Web. 28 Feb 2021.

Vancouver:

Chakravarthy H. The role of altered sphingolipid metabolism in the development of diabetic retinopathy. [Internet] [Thesis]. Michigan State University; 2015. [cited 2021 Feb 28]. Available from: http://etd.lib.msu.edu/islandora/object/etd:3586.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Chakravarthy H. The role of altered sphingolipid metabolism in the development of diabetic retinopathy. [Thesis]. Michigan State University; 2015. Available from: http://etd.lib.msu.edu/islandora/object/etd:3586

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Aberdeen

21. Wirrig, Christiane. Effects of sphingolipids on the inflammatory reactivity of vascular smooth muscle cells.

Degree: PhD, 2012, University of Aberdeen

URL: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12152414290005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558636

► Cardiovascular diseases are a major cause of death worldwide. Aneurysmal rupture in cerebral arteries or loss of endothelial integrity in the course of atherosclerosis or… (more)

▼ Cardiovascular diseases are a major cause of death worldwide. Aneurysmal rupture in cerebral arteries or loss of endothelial integrity in the course of atherosclerosis or therapeutic angioplasty lead to exposure of vascular smooth muscle cells (SMC) to blood components such as sphingolipids. Sphingosylphosphorylcholine (SPC) and sphingosine 1-phosphate (S1P) are two naturally occurring sphingolipids, which are vasoprotective in the healthy endothelium-lined vessel, but may promote vascular disease by causing functional changes of SMC. Vascular inflammation is an important factor in various pathologies. SPC can activate pro-inflammatory signalling pathways in rat cerebral artery. Here these observations are extended by showing that SPC elicits monocyte chemoattractant protein-1 production in rat cerebral artery SMC ex vivo. Thus, in addition to being a vasoconstrictor, SPC may promote the development of life-threatening prolonged cerebral vasospasm following subarachnoid haemorrhage by supporting vascular inflammation. It is also demonstrated that SPC prevents tumour necrosis factor-a (TNF)-stimulated adhesion of macrophages to rat aortic SMC in vitro by interfering with adhesive properties of SMC, but not macrophages. While this effect appeared to be mediated by the S1P receptor S1P2, S1P itself did not reduce macrophage adhesion. The anti-adhesive action of SPC also depended on lipid rafts. However, SPC did neither prevent TNF-induced nuclear factor kB activation nor cell adhesion molecule expression in SMC. SPC-induced cyclooxygenase 2 expression in aortic SMC was dispensable for its anti-adhesive effect. In contrast, the inhibitory effect of SPC on TNFinduced expression of inducible nitric oxide synthase is probably involved in its anti-adhesive effect because it was mimicked by respective pharmacological blockade. The results also demonstrate that nitric oxide promotes leukocyte adhesion to vascular SMC, while it has the opposite effect on endothelial cells. These findings may help understand cardiovascular diseases and define novel treatment approaches.

Subjects/Keywords: 616.1; Vascular smooth muscle; Sphingolipids; Atherosclerosis

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APA (6^th Edition):

Wirrig, C. (2012). Effects of sphingolipids on the inflammatory reactivity of vascular smooth muscle cells. (Doctoral Dissertation). University of Aberdeen. Retrieved from https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12152414290005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558636

Chicago Manual of Style (16^th Edition):

Wirrig, Christiane. “Effects of sphingolipids on the inflammatory reactivity of vascular smooth muscle cells.” 2012. Doctoral Dissertation, University of Aberdeen. Accessed February 28, 2021. https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12152414290005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558636.

MLA Handbook (7^th Edition):

Wirrig, Christiane. “Effects of sphingolipids on the inflammatory reactivity of vascular smooth muscle cells.” 2012. Web. 28 Feb 2021.

Vancouver:

Wirrig C. Effects of sphingolipids on the inflammatory reactivity of vascular smooth muscle cells. [Internet] [Doctoral dissertation]. University of Aberdeen; 2012. [cited 2021 Feb 28]. Available from: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12152414290005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558636.

Council of Science Editors:

Wirrig C. Effects of sphingolipids on the inflammatory reactivity of vascular smooth muscle cells. [Doctoral Dissertation]. University of Aberdeen; 2012. Available from: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12152414290005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558636

University of Gothenburg / Göteborgs Universitet

22. Samuelsson, Bo E., 1942-. On the structure and function of sphingolipids.

Degree: 1973, University of Gothenburg / Göteborgs Universitet

URL: http://hdl.handle.net/2077/13977

Subjects/Keywords: Medicin Allmänt Sphingolipids: anatomy & histology; Sphingolipids: physiology

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APA (6^th Edition):

Samuelsson, Bo E., 1. (1973). On the structure and function of sphingolipids. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/13977

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Samuelsson, Bo E., 1942-. “On the structure and function of sphingolipids.” 1973. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed February 28, 2021. http://hdl.handle.net/2077/13977.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Samuelsson, Bo E., 1942-. “On the structure and function of sphingolipids.” 1973. Web. 28 Feb 2021.

Vancouver:

Samuelsson, Bo E. 1. On the structure and function of sphingolipids. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 1973. [cited 2021 Feb 28]. Available from: http://hdl.handle.net/2077/13977.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Samuelsson, Bo E. 1. On the structure and function of sphingolipids. [Thesis]. University of Gothenburg / Göteborgs Universitet; 1973. Available from: http://hdl.handle.net/2077/13977

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

23. OH JEONGAH. SPHINGOLIPID INVENTORY AND VARIABILITY IN HUMAN PLATELETS.

Degree: 2019, National University of Singapore

URL: https://scholarbank.nus.edu.sg/handle/10635/164739

Subjects/Keywords: Lipidomics; Sphingolipids; Sphingolipidomics; Platelets; Platelet sphingolipids; Platelet lipidomics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

JEONGAH, O. (2019). SPHINGOLIPID INVENTORY AND VARIABILITY IN HUMAN PLATELETS. (Thesis). National University of Singapore. Retrieved from https://scholarbank.nus.edu.sg/handle/10635/164739

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

JEONGAH, OH. “SPHINGOLIPID INVENTORY AND VARIABILITY IN HUMAN PLATELETS.” 2019. Thesis, National University of Singapore. Accessed February 28, 2021. https://scholarbank.nus.edu.sg/handle/10635/164739.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

JEONGAH, OH. “SPHINGOLIPID INVENTORY AND VARIABILITY IN HUMAN PLATELETS.” 2019. Web. 28 Feb 2021.

Vancouver:

JEONGAH O. SPHINGOLIPID INVENTORY AND VARIABILITY IN HUMAN PLATELETS. [Internet] [Thesis]. National University of Singapore; 2019. [cited 2021 Feb 28]. Available from: https://scholarbank.nus.edu.sg/handle/10635/164739.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

JEONGAH O. SPHINGOLIPID INVENTORY AND VARIABILITY IN HUMAN PLATELETS. [Thesis]. National University of Singapore; 2019. Available from: https://scholarbank.nus.edu.sg/handle/10635/164739

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Georgia Tech

24. Ozbay, Tuba Selcuk. The Role of Sphingolipids in Cortisol Synthesis in the Adrenal Cortex.

Degree: MS, Biology, 2005, Georgia Tech

URL: http://hdl.handle.net/1853/7549

► In the human adrenal cortex, adrenocorticotropin (ACTH) activates steroid hormone biosynthesis by acutely increasing cholesterol delivery to the mitochondria and chronically up-regulating the transcription of… (more)

▼ In the human adrenal cortex, adrenocorticotropin (ACTH) activates steroid hormone biosynthesis by acutely increasing cholesterol delivery to the mitochondria and chronically up-regulating the transcription of steroidogenic genes (including CYP17). Sphingolipids are a diverse family of phospholipids and glycolipids that mediate a wide variety of cellular processes, including apoptosis, proliferation, and survival. Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors that regulate genes that are involved in cholesterol biosynthesis and fatty acid metabolism. In this study, we investigated the role of sphingolipids in ACTH-dependent steroidogenesis. H295R human adrenocortical cells were treated with ACTH or dibutyryl cAMP (Bt2cAMP) for various time periods and the content of several sphingolipid species was quantified by mass spectrometry. Both ACTH and Bt2cAMP decreased cellular amounts of sphingomyelin, ceramides, sphingosine (So) and sphingosine-1-phosphate (S1P). However, both ACTH and Bt2cAMP increased the activity of sphingosine kinase and the amounts of S1P released into the media. Both So and S1P increased CYP17 mRNA expression and increased cortisol biosynthesis. This increase in CYP17 transcription occurs by promoting SREBP binding to an SRE at -450/-436 basepairs upstream of the transcription initiation site. Furthermore, chromatin immunoprecipitation (ChIP) assays revealed that Bt2cAMP and S1P treatment results in an increase in acetylation of histone H3 and SREBP1 binding to CYP17 promoter. Additionally, transient transfection studies using wild type or mutated hCYP17 promoters and RNA interference (RNAi) assays confirmed the role of SREBP1 in mediating the stimulatory effect of S1P on CYP17 transcription. In summary, our studies demonstrate a link between sphingolipid metabolism and ACTH-dependent steroidogenesis which requires the activation of SREBP1 in human adrenal cortex. Advisors/Committee Members: Sewer, Marion B. (Committee Chair), Boyan, Barbara D. (Committee Member), Merrill, Alfred H. (Committee Member), Radhakrishna, Harish (Committee Member).

Subjects/Keywords: SREBP; S1P; CYP17; Sphingolipids; Adrenal cortex; Sphingolipids

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APA (6^th Edition):

Ozbay, T. S. (2005). The Role of Sphingolipids in Cortisol Synthesis in the Adrenal Cortex. (Masters Thesis). Georgia Tech. Retrieved from http://hdl.handle.net/1853/7549

Chicago Manual of Style (16^th Edition):

Ozbay, Tuba Selcuk. “The Role of Sphingolipids in Cortisol Synthesis in the Adrenal Cortex.” 2005. Masters Thesis, Georgia Tech. Accessed February 28, 2021. http://hdl.handle.net/1853/7549.

MLA Handbook (7^th Edition):

Ozbay, Tuba Selcuk. “The Role of Sphingolipids in Cortisol Synthesis in the Adrenal Cortex.” 2005. Web. 28 Feb 2021.

Vancouver:

Ozbay TS. The Role of Sphingolipids in Cortisol Synthesis in the Adrenal Cortex. [Internet] [Masters thesis]. Georgia Tech; 2005. [cited 2021 Feb 28]. Available from: http://hdl.handle.net/1853/7549.

Council of Science Editors:

Ozbay TS. The Role of Sphingolipids in Cortisol Synthesis in the Adrenal Cortex. [Masters Thesis]. Georgia Tech; 2005. Available from: http://hdl.handle.net/1853/7549

25. Rodrigo Alcantara de Carvalho. Avaliação do biomarcador (esfinganina/esfingosina) como fator de exposição às fumonisinas em frangos de corte.

Degree: 2006, Universidade Federal Rural do Rio de Janeiro

URL: http://bdtd.ufrrj.br//tde_busca/arquivo.php?codArquivo=743

►

A contaminação mundial de alimentos e subprodutos com micotoxinas é um problema de extrema importância. As micotoxinas são metabólitos secundários produzidos por fungos, que possuem… (more)

▼

A contaminação mundial de alimentos e subprodutos com micotoxinas é um problema de extrema importância. As micotoxinas são metabólitos secundários produzidos por fungos, que possuem efeitos adversos à saúde humana e animal. As fumonisinas e aflatoxinas são as micotoxinas de maior importância agro-econômica pelos prejuízos acarretados à produção animal. Passos importantes na síntese destas micotoxinas são descritos, assim como seu metabolismo e efeitos adversos. Este trabalho avalia a determinação dos biomarcadores esfinganina (Sa) e esfingosina (So) no soro de frangos de corte como método de diagnóstico para exposição às fumonisinas e compara os dados obtidos com a análise da ração. Dos animais avaliados apenas 49% exibiram quantidades detectáveis de esfingolipídeos no soro, dentre estes, apenas 44,9% exibiram os 2 esfingolipídeos (Sa e So), 53,06% exibiram somente So e 2,04% exibiram somente Sa. Foi detectada na ração a presença de fumonisina B1 na concentração de 374,92μg.kg-1 e de aflatoxinas B1, B2 e G1 nas concentrações de 440,99μg.kg-1, 169,92μg.kg-1 e 494,58μg.kg-1, respectivamente. Foi possível estabelecer parcialmente o grau de intoxicação dos frangos e verificar que a sensibilidade do biomarcador pode ser afetada tanto pela presença de fumonisina quanto de aflatoxina.

The world wide contamination of foods and byproducts with mycotoxins is a problem of extreme importance. Mycotoxins are secondary metabolites produced by fungi that have adverse effects to human and animal health. The fumonisins and aflatoxins are the mycotoxins of greatest agro-economic importance due to the damage brought to animal production. Important steps in the synthesis of these mycotoxins are described, as such as their metabolism and adverse effects. This work evaluates the determination of the biomarkers sphinganin (Sa) and sphingosin (So) in poultry serum as a diagnose method for fumonisin exposition, and compares the obtained data with ration analysis. Of the evaluated animals only 49% exhibited 2 sphingolipids (Sa and So), 53,04% exhibited only So and 2,04% exhibited only Sa. It was detected at ration the presence of fumonisin B1 at concentration of 374,92μg.kg-1 and aflatoxins B1, B2, and G1 at concentrations of 440,99μg.kg-1, 169,92μg.kg-1 and 494,58μg.kg-1, respectively. It was possible to partially establish the grade of intoxication of the poultry and to verify that the sensibility of the biomarker can be affected by the presence of fumonisin such as aflatoxins.

Advisors/Committee Members: Glória Maria Direito.

Subjects/Keywords: fumonisinas; aflatoxinas; esfingolipídeos; MEDICINA VETERINARIA; fumonisins; aflatoxins; sphingolipids

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APA (6^th Edition):

Carvalho, R. A. d. (2006). Avaliação do biomarcador (esfinganina/esfingosina) como fator de exposição às fumonisinas em frangos de corte. (Thesis). Universidade Federal Rural do Rio de Janeiro. Retrieved from http://bdtd.ufrrj.br//tde_busca/arquivo.php?codArquivo=743

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Carvalho, Rodrigo Alcantara de. “Avaliação do biomarcador (esfinganina/esfingosina) como fator de exposição às fumonisinas em frangos de corte.” 2006. Thesis, Universidade Federal Rural do Rio de Janeiro. Accessed February 28, 2021. http://bdtd.ufrrj.br//tde_busca/arquivo.php?codArquivo=743.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Carvalho, Rodrigo Alcantara de. “Avaliação do biomarcador (esfinganina/esfingosina) como fator de exposição às fumonisinas em frangos de corte.” 2006. Web. 28 Feb 2021.

Vancouver:

Carvalho RAd. Avaliação do biomarcador (esfinganina/esfingosina) como fator de exposição às fumonisinas em frangos de corte. [Internet] [Thesis]. Universidade Federal Rural do Rio de Janeiro; 2006. [cited 2021 Feb 28]. Available from: http://bdtd.ufrrj.br//tde_busca/arquivo.php?codArquivo=743.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Carvalho RAd. Avaliação do biomarcador (esfinganina/esfingosina) como fator de exposição às fumonisinas em frangos de corte. [Thesis]. Universidade Federal Rural do Rio de Janeiro; 2006. Available from: http://bdtd.ufrrj.br//tde_busca/arquivo.php?codArquivo=743

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

26. Schofield, Jonathan David. HDL Functionality and Lipoprotein Quality in Diabetes Mellitus.

Degree: 2017, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:308003

► Background & AimsThe ‘high-density lipoprotein (HDL) hypothesis’, that therapeutic interventions directed at raising HDL cholesterol might translate into improved cardiovascular outcomes, has been confounded by… (more)

▼ Background & AimsThe ‘high-density lipoprotein (HDL) hypothesis’, that therapeutic interventions directed at raising HDL cholesterol might translate into improved cardiovascular outcomes, has been confounded by recent reports from genetic and pharmacological studies. HDL functionality may be more important than cholesterol cargo. HDL cholesterol levels are normal or even high in Type 1 Diabetes (T1DM) but do not seem to protect against atherosclerosis as might be expected; this thesis aims to offer new insight into HDL functionality through examination of these patients. This thesis also aims to improve understanding of the qualitative changes in lipoproteins associated with diabetes and increased cardiovascular morbidity, with emphasis on atherogenic modifications of apolipoprotein B and sphingolipids, and consideration of the relationship between these changes, novel and established biomarkers, and macrovascular and microvascular diabetic complications. Materials & MethodsPatients with Type 1 (n = 91) and Type 2 (n = 40) Diabetes Mellitus and healthy volunteers (n = 104) attended for fasting blood tests, urinalysis, and examination including cardiac computed tomography, carotid doppler studies and assessments of nerve function. In vitro studies of lipoprotein modification used pooled human plasma. ResultsLipoprotein glycation represents an atherogenic modification. In vitro glycation occurs more readily in the presence of physiological concentrations of copper. HDL and copper-selective chelation with triethylenetetramine prevents glycation. Glycated apolipoprotein B, oxidized LDL and small-dense LDL levels were significantly higher in T1DM; HDL cholesterol levels were also significantly higher, but with altered apolipoprotein distribution, and significantly lower cholesterol efflux capacity and PON1 activity than in healthy controls. Significant changes were also observed in cystatin C, advanced glycation end-products, leucine-rich α-2-glycoprotein, lipoprotein-associated phospholipase A2, a variety of inflammatory markers, and sphingolipid and ceramide profiles.DiscussionCardiovascular disease is the leading cause of death and disability in diabetes. Patients with diabetes show qualitative and kinetic lipoprotein abnormalities, and any cardiovascular benefit associated with intensive glucose lowering may be related to effects on lipoprotein metabolism rather than directly through altered glycaemia. The apparently relatively undisturbed lipid profile observed in many patients with diabetes hides major atherogenic changes and altered HDL functionality, which may be at least partially responsible for the persistent increased risk of cardiovascular disease in patients with diabetes. HDL-based therapy remains a largely unfulfilled promise, but there may be a role for copper-selective chelation and more aggressive low-density lipoprotein lowering in the reduction of diabetic complications. Advisors/Committee Members: MALIK, RAYAZ RA, Malik, Rayaz, Soran, Handrean.

Subjects/Keywords: Diabetes Mellitus; HDL Functionality; LDL Quality; Sphingolipids; Ceramides

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APA (6^th Edition):

Schofield, J. D. (2017). HDL Functionality and Lipoprotein Quality in Diabetes Mellitus. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:308003

Chicago Manual of Style (16^th Edition):

Schofield, Jonathan David. “HDL Functionality and Lipoprotein Quality in Diabetes Mellitus.” 2017. Doctoral Dissertation, University of Manchester. Accessed February 28, 2021. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:308003.

MLA Handbook (7^th Edition):

Schofield, Jonathan David. “HDL Functionality and Lipoprotein Quality in Diabetes Mellitus.” 2017. Web. 28 Feb 2021.

Vancouver:

Schofield JD. HDL Functionality and Lipoprotein Quality in Diabetes Mellitus. [Internet] [Doctoral dissertation]. University of Manchester; 2017. [cited 2021 Feb 28]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:308003.

Council of Science Editors:

Schofield JD. HDL Functionality and Lipoprotein Quality in Diabetes Mellitus. [Doctoral Dissertation]. University of Manchester; 2017. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:308003

Penn State University

27. Tan, Su-fern. Role of Acid Ceramidase in Regulating Survival and Drug Resistance in Acute Myeloid Leukemia.

Degree: 2013, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/19626

► Acute myeloid leukemia (AML) is a heterogeneous disease that affects the differentiation of myeloid precursors. In normal hematopoiesis, hematopoietic stem cells committed to the myeloid… (more)

▼ Acute myeloid leukemia (AML) is a heterogeneous disease that affects the differentiation of myeloid precursors. In normal hematopoiesis, hematopoietic stem cells committed to the myeloid lineage form platelets, white cells and red cells. AML patients have the characteristic feature of accumulated immature myeloid precursors known as blasts. Prognosis for AML patients depends on several risk factors, including cytogenetic abnormalities, age, prior exposure to chemotherapy, and pre-existing hematological disorder such as myelodysplastic syndrome (MDS). The five-year survival rate for AML patients remains low and drug resistance is also a major problem for relapsed patients. Hence, AML patients require better treatments. Sphingolipids are a group of sphingoid-based lipids that maintain cellular integrity and mediate signal transduction and gene regulation. Two sphingolipids are important in regulating cell survival: ceramide and sphingosine-1-phosphate (S1P). The ceramide and S1P balance is known as the “sphingolipid rheostat”, which modulates cell survival. Sphingolipids are dysregulated in many types of cancer, including AML. Acid ceramidase (AC) is a lysosomal enzyme that catalyzes ceramide breakdown into sphingosine and free fatty acids. Sphingosine is then phosphorylated by sphingosine kinases to form S1P. AC is crucial for embryonic development but is found in high levels in several different types of cancer, including prostate, colon and breast cancer. In this study, we investigated the role of AC in AML blast survival and drug resistance. We show that AC expression and activity is elevated in AML patients. Corresponding to elevated AC activity is the elevation of S1P levels also detected in patient samples. Targeting AC using ceramide analog LCL204 and AC shRNA decreased viability and myeloid cell leukemia differentiation protein-1(Mcl-1) expression, a B-cell lymphoma 2 (Bcl-2) family protein essential for AML survival. AC inhibition also decreased the multidrug resistance protein (MDR1)/P-glycoprotein (P-gp) and sensitized cells to AML chemotherapeutic drugs. Furthermore, AC overexpression in AML cell line HL-60 increased S1P and decreased total ceramide levels. We also found that AC overexpression increased NF-κB activation, a transcription factor responsible for many survival pathways including the regulation of Mcl-1 and P-gp transcription. We hypothesized that AC overexpression increases NF-κB activation that then serves as a positive feedback loop back to AC. We demonstrate that NF-κB inhibition decreased AC, Mcl-1 and P-gp expression, supporting the positive feedback loop hypothesis. Pharmacological inhibition of AC in a murine AML model also significantly increased the survival of leukemic mice. Taken together, we show that AC is important for blast survival and drug resistance in AML. Targeting AC changes the sphingolipid rheostat to increase ceramide and decrease S1P levels, thereby leading to cell death. We also demonstrate for the first time that AC regulates Mcl-1 and P-gp expression,… Advisors/Committee Members: Andrew Paul Loughran, Dissertation Advisor/Co-Advisor, "Thomas P Loughran, Jr", Committee Chair/Co-Chair, Charles H Lang, Committee Chair/Co-Chair, Hong Gang Wang, Committee Member, Jin Ming Yang, Committee Member, David F Claxton, Special Member.

Subjects/Keywords: AML; Acid Ceramidase; Mcl-1; P-glycoprotein; NF-kB; sphingolipids

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APA (6^th Edition):

Tan, S. (2013). Role of Acid Ceramidase in Regulating Survival and Drug Resistance in Acute Myeloid Leukemia. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/19626

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Tan, Su-fern. “Role of Acid Ceramidase in Regulating Survival and Drug Resistance in Acute Myeloid Leukemia.” 2013. Thesis, Penn State University. Accessed February 28, 2021. https://submit-etda.libraries.psu.edu/catalog/19626.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Tan, Su-fern. “Role of Acid Ceramidase in Regulating Survival and Drug Resistance in Acute Myeloid Leukemia.” 2013. Web. 28 Feb 2021.

Vancouver:

Tan S. Role of Acid Ceramidase in Regulating Survival and Drug Resistance in Acute Myeloid Leukemia. [Internet] [Thesis]. Penn State University; 2013. [cited 2021 Feb 28]. Available from: https://submit-etda.libraries.psu.edu/catalog/19626.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Tan S. Role of Acid Ceramidase in Regulating Survival and Drug Resistance in Acute Myeloid Leukemia. [Thesis]. Penn State University; 2013. Available from: https://submit-etda.libraries.psu.edu/catalog/19626

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Toronto

28. Rovic, Isidora. The Role of Acid Sphingomyelinase in Murine Placental Development.

Degree: 2018, University of Toronto

URL: http://hdl.handle.net/1807/97673

►

Sphingolipids are a diverse class of bioactive signaling lipids that control an array of fundamental cellular processes. Recently, dysregulation of sphingolipid metabolism has been observed… (more)

Subjects/Keywords: acid sphingomyelinase; autophagy; fetal growth restriction; placenta; sphingolipids; 0719

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Rovic, I. (2018). The Role of Acid Sphingomyelinase in Murine Placental Development. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/97673

Chicago Manual of Style (16^th Edition):

Rovic, Isidora. “The Role of Acid Sphingomyelinase in Murine Placental Development.” 2018. Masters Thesis, University of Toronto. Accessed February 28, 2021. http://hdl.handle.net/1807/97673.

MLA Handbook (7^th Edition):

Rovic, Isidora. “The Role of Acid Sphingomyelinase in Murine Placental Development.” 2018. Web. 28 Feb 2021.

Vancouver:

Rovic I. The Role of Acid Sphingomyelinase in Murine Placental Development. [Internet] [Masters thesis]. University of Toronto; 2018. [cited 2021 Feb 28]. Available from: http://hdl.handle.net/1807/97673.

Council of Science Editors:

Rovic I. The Role of Acid Sphingomyelinase in Murine Placental Development. [Masters Thesis]. University of Toronto; 2018. Available from: http://hdl.handle.net/1807/97673

Université de Lorraine

29. Orsini, Marion. Inhibition de l’érythropoïèse par la voie TNFα/sphingomyélinase/céramide : rôle du réseau de régulation microARN/facteurs de transcription et impact sur l’autophagie : TNFα/sphingomyelinase/ceramide pathway-mediated inhibition of erythropoiesis : role of microRNA/transcription factor network and impact on autophagy.

Degree: Docteur es, Sciences de la vie et de la santé, 2017, Université de Lorraine

URL: http://www.theses.fr/2017LORR0225

►

L’anémie est un symptôme fréquent chez les patients atteints de cancer. La libération de la cytokine pro-inflammatoire TNFα, un inhibiteur connu de l’érythropoïèse, en est… (more)

▼

L’anémie est un symptôme fréquent chez les patients atteints de cancer. La libération de la cytokine pro-inflammatoire TNFα, un inhibiteur connu de l’érythropoïèse, en est l’une des causes. L’érythropoïèse est un processus nécessitant l’arrêt de la prolifération et l’autophagie. Les résultats précédents ont montré que le TNFα inhibe l’expression des marqueurs érythroïdes et module l’expression de facteurs de transcription (FT) hématopoïétiques. Notre objectif est d’étudier l’implication de la voie TNFα/sphingomyélinase (SMase)/céramide dans l’inhibition de l’érythropoïèse en utilisant des cellules souches hématopoïétiques CD34+ induites à se différencier par l’érythropoïétine recombinante (Epo). Par l’utilisation de céramides exogènes, de SMase bactérienne et d’inhibiteurs de SMases, nous montrons l’implication de la voie SMase/céramide dans l’inhibition de l’expression des marqueurs érythroïdes mais également dans l’induction de la différenciation myéloïde avec une augmentation de l’expression du CD11b. Cet effet sur la différenciation est corrélé à la modulation du réseau FT/miR impliquant GATA-1, GATA-2 et PU.1 et les miR-144, 451, 155, 146a et 223. De plus, l’analyse par microscopie électronique à transmission, l’absence de formation de punctae GFP-LC3 et l’accumulation de SQSTM1/p62 montrent que le TNFα et les céramides inhibent l’autophagie induite par l’Epo. L’analyse des protéines impliquées dans la régulation de l’autophagie montre que le TNFα et les céramides activent mTOR. Son implication est confirmée par l’utilisation de rapamycine et l’inhibition de ULK1 et Atg13. De plus, le TNFα et les céramides inhibent l’expression de bécline 1 et de la formation du complexe Atg5-Atg12. Ces résultats démontrent que la voie TNFα/SMase/céramide joue un rôle dans l’homéostasie hématopoïétique par l’inhibition de l’érythropoïèse au profit de la myélopoïèse, en impactant les réseaux de régulation FT/miR et le processus d’autophagie

Anemia is a common symptom in cancer patients. It can be caused by the release of pro-inflammatory cytokines such as TNFα, a known inhibitor of erythropoiesis. Erythropoiesis involves proliferation arrest and autophagy. Our previous studies showed that TNFα inhibits the expression of erythroid markers as well as hematopoietic transcription factors (TF) expression. The aim is to study the involvement of TNFα/sphingomyelinase (SMase)/ceramide pathway in erythropoiesis inhibition using recombinant erythropoietin (Epo)-induced CD34+ hematopoietic stem cells. Using exogenous ceramides, a bacterial SMase and sphingomyelinase inhibitors, we show the involvement of SMase/ceramide pathway in the inhibition of erythroid markers as well as the induction of myeloid differentiation as shown by the increase in CD11b expression. This effect is correlated to the modulation of the TF/miR network involving GATA-1, GATA-2 and PU.1 as well as miR-144, 451, 155, 146a and 223. We show that TNFα and ceramides inhibit Epo-induced autophagy through transmission electron microscopy analysis, the absence of GFP-LC3…

Advisors/Committee Members: Diederich, Marc (thesis director), Morceau, Franck (thesis director).

Subjects/Keywords: TNFα; Sphingolipides; Érythropoïèse; Myélopoïèse; Autophagie; TNFα; Sphingolipids; Erythropoiesis; Myelopoiesis; Autophagy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Orsini, M. (2017). Inhibition de l’érythropoïèse par la voie TNFα/sphingomyélinase/céramide : rôle du réseau de régulation microARN/facteurs de transcription et impact sur l’autophagie : TNFα/sphingomyelinase/ceramide pathway-mediated inhibition of erythropoiesis : role of microRNA/transcription factor network and impact on autophagy. (Doctoral Dissertation). Université de Lorraine. Retrieved from http://www.theses.fr/2017LORR0225

Chicago Manual of Style (16^th Edition):

Orsini, Marion. “Inhibition de l’érythropoïèse par la voie TNFα/sphingomyélinase/céramide : rôle du réseau de régulation microARN/facteurs de transcription et impact sur l’autophagie : TNFα/sphingomyelinase/ceramide pathway-mediated inhibition of erythropoiesis : role of microRNA/transcription factor network and impact on autophagy.” 2017. Doctoral Dissertation, Université de Lorraine. Accessed February 28, 2021. http://www.theses.fr/2017LORR0225.

MLA Handbook (7^th Edition):

Orsini, Marion. “Inhibition de l’érythropoïèse par la voie TNFα/sphingomyélinase/céramide : rôle du réseau de régulation microARN/facteurs de transcription et impact sur l’autophagie : TNFα/sphingomyelinase/ceramide pathway-mediated inhibition of erythropoiesis : role of microRNA/transcription factor network and impact on autophagy.” 2017. Web. 28 Feb 2021.

Vancouver:

Orsini M. Inhibition de l’érythropoïèse par la voie TNFα/sphingomyélinase/céramide : rôle du réseau de régulation microARN/facteurs de transcription et impact sur l’autophagie : TNFα/sphingomyelinase/ceramide pathway-mediated inhibition of erythropoiesis : role of microRNA/transcription factor network and impact on autophagy. [Internet] [Doctoral dissertation]. Université de Lorraine; 2017. [cited 2021 Feb 28]. Available from: http://www.theses.fr/2017LORR0225.

Council of Science Editors:

Orsini M. Inhibition de l’érythropoïèse par la voie TNFα/sphingomyélinase/céramide : rôle du réseau de régulation microARN/facteurs de transcription et impact sur l’autophagie : TNFα/sphingomyelinase/ceramide pathway-mediated inhibition of erythropoiesis : role of microRNA/transcription factor network and impact on autophagy. [Doctoral Dissertation]. Université de Lorraine; 2017. Available from: http://www.theses.fr/2017LORR0225

30. S. Grassi. IDENTIFICATION OF THE ANTIGEN RECOGNIZED BY RHIGM22, A REMYELINATION-PROMOTING HUMAN MONOCLONAL ANTIBODY.

Degree: 2017, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/476059

► Oligodendrocytes (OLs) are the myelin-forming cells of the central nervous system (CNS). They synthesize large amounts of plasma membrane and extends multiple processes that individually… (more)

▼ Oligodendrocytes (OLs) are the myelin-forming cells of the central nervous system (CNS). They synthesize large amounts of plasma membrane and extends multiple processes that individually wrap around axons generating a multilayered stack of membranes tightly attached at their cytosolic and external surfaces, i.e. myelin. The myelin membrane provides electric insulation of axons and dictates the clustering of the sodium channels at the nodes of Ranvier and the organization of the node itself, allowing saltatory nerve conduction. A number of neurological diseases of the CNS are characterized by destruction of oligodendrocytes with consequent damage or loss of the myelin sheath. In most experimental models, the normal response to this is remyelination, a process mediated by oligodendrocyte precursor cells (OPC) that ultimately leads to functional recovery. However in human diseases, and in specific in multiple sclerosis (MS), this process is inefficient and fails to successfully counteract the accumulation of lasting axonal damage and increasing brain atrophy, thus resulting in motor and neurological deficits. The development of strategies aimed to increase the efficiency of the remyelination process is therefore an important therapeutic goal. One of these strategies involves the use of CNS reactive antibodies to promote remyelination. One of these antibodies, rHIgM22, is able to bind to oligodendrocytes and myelin in vitro. Moreover, rHIgM22 is able to enter the CNS, accumulate at lesion site and promote remyelination in mouse models of chronical demyelination. As a matter of fact, this antibody has recently passed a phase I clinical trial for treatment of MS. rHIgM22 binds to CNS tissues with a pattern very similar to that of the anti-sulfatide antibody O4, and binding of rHIgM22 is abolished in CNS tissue slices from CST (-/-) mice, suggesting that rHIgM22 binding to myelin requires the presence of a product of cerebroside sulfotransferase, possibly sulfatide. However the exact identity of the antigen recognized by this antibody remains to be elucidated. The binding of rHIgM22 to purified lipids and to lipid extracts from various sources, including wild type, ASM (-/-), CST (+/-) and CST (-/-) mice brains, mouse mixed glial cells (MGC), mouse astrocytes, rat rHIgM22+ oligodendrocytes (OL), rat microglia, and mouse myelin, has been tested using TLC immunostaining assays and SPR experiments with lipid monolayers with different composition. The results obtained show that rHIgM22 binds to sulfatide, and, to a lesser extent, to lysosulfatide in vitro, while it does not bind to other myelin sphingolipids, including galactosylceramide and sphingomyelin, suggesting that sulfatide at the oligodendrocyte surface might be important for the binding of rHIgM22 to the surface of these cells and to myelin. The binding affinity for both sulfatide and its deacylated derivate is low, even if the binding is specific. On the other hand, our data shows that the binding affinity of rHIgM22 for sulfatide can be modulated by the presence… Advisors/Committee Members: docente guida: A. Prinetti, coordinatore: S. Sonnino, PRINETTI, ALESSANDRO ENNIO GIUSEPPE, SONNINO, SANDRO.

Subjects/Keywords: Multiple sclerosis; sulfatide; sphingolipids; remyelination; Settore BIO/10 - Biochimica

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Grassi, S. (2017). IDENTIFICATION OF THE ANTIGEN RECOGNIZED BY RHIGM22, A REMYELINATION-PROMOTING HUMAN MONOCLONAL ANTIBODY. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/476059

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Grassi, S.. “IDENTIFICATION OF THE ANTIGEN RECOGNIZED BY RHIGM22, A REMYELINATION-PROMOTING HUMAN MONOCLONAL ANTIBODY.” 2017. Thesis, Università degli Studi di Milano. Accessed February 28, 2021. http://hdl.handle.net/2434/476059.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Grassi, S.. “IDENTIFICATION OF THE ANTIGEN RECOGNIZED BY RHIGM22, A REMYELINATION-PROMOTING HUMAN MONOCLONAL ANTIBODY.” 2017. Web. 28 Feb 2021.

Vancouver:

Grassi S. IDENTIFICATION OF THE ANTIGEN RECOGNIZED BY RHIGM22, A REMYELINATION-PROMOTING HUMAN MONOCLONAL ANTIBODY. [Internet] [Thesis]. Università degli Studi di Milano; 2017. [cited 2021 Feb 28]. Available from: http://hdl.handle.net/2434/476059.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Grassi S. IDENTIFICATION OF THE ANTIGEN RECOGNIZED BY RHIGM22, A REMYELINATION-PROMOTING HUMAN MONOCLONAL ANTIBODY. [Thesis]. Università degli Studi di Milano; 2017. Available from: http://hdl.handle.net/2434/476059

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Open Access Theses and Dissertations