The Experts below are selected from a list of 58143 Experts worldwide ranked by ideXlab platform
Luanne L. Peters - One of the best experts on this subject based on the ideXlab platform.
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strain specific hyperkyphosis and megaesophagus in add1 null mice
Genesis, 2012Co-Authors: Raymond F. Robledo, Kevin L. Seburn, Anthony Nicholson, Luanne L. PetersAbstract:The three adducin proteins (α, β, and γ) share extensive sequence, structural, and functional homology. Heterodimers of α- and β-adducin are vital components of the red cell membrane skeleton, which is required to maintain red cell elasticity and structural integrity. In addition to anemia, targeted deletion of the α-adducin gene (Add1) reveals unexpected, strain-dependentnon-erythroid phenotypes. On an inbred 129 genetic background, Add1 null mice show abnormal inward curvature of the cervicothoracic spine with complete penetrance. More surprisingly, a subset of 129-Add1 null mice develop severe megaesophagus, while examination of peripheral nerves reveals a reduced number of axons in 129-Add1 null mice at four months of age. These unforeseen phenotypes, described here, reveal new functions for adducin and provide new models of Mammalian Disease. genesis 50:882–891, 2012. © 2012 Wiley Periodicals, Inc.
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Strain-specific hyperkyphosis and megaesophagus in Add1 null mice.
Genesis (New York N.Y. : 2000), 2012Co-Authors: Raymond F. Robledo, Kevin L. Seburn, Anthony Nicholson, Luanne L. PetersAbstract:The three adducin proteins (α, β, and γ) share extensive sequence, structural, and functional homology. Heterodimers of α- and β-adducin are vital components of the red cell membrane skeleton, which is required to maintain red cell elasticity and structural integrity. In addition to anemia, targeted deletion of the α-adducin gene (Add1) reveals unexpected, strain-dependent non-erythroid phenotypes. On an inbred 129 genetic background, Add1 null mice show abnormal inward curvature of the cervicothoracic spine with complete penetrance. More surprisingly, a subset of 129-Add1 null mice develop severe megaesophagus, while examination of peripheral nerves reveals a reduced number of axons in 129-Add1 null mice at four months of age. These unforeseen phenotypes, described here, reveal new functions for adducin and provide new models of Mammalian Disease.
Bradley K Yoder - One of the best experts on this subject based on the ideXlab platform.
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an incredible decade for the primary cilium a look at a once forgotten organelle
American Journal of Physiology-renal Physiology, 2005Co-Authors: James R Davenport, Bradley K YoderAbstract:Since the discovery that numerous proteins involved in Mammalian Disease localize to the basal bodies and cilia, these organelles have emerged from relative obscurity to the center of intense resea...
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an incredible decade for the primary cilium a look at a once forgotten organelle
American Journal of Physiology-renal Physiology, 2005Co-Authors: James R Davenport, Bradley K YoderAbstract:Since the discovery that numerous proteins involved in Mammalian Disease localize to the basal bodies and cilia, these organelles have emerged from relative obscurity to the center of intense research efforts in an expanding number of Disease- and developmental-related fields. Our understanding of the association between cilia and human Disease has benefited substantially from the use of lower organisms such as Chlamydomonas and Caenorhabditis elegans and the availability of murine models and cell culture. These research endeavors led to the discovery that loss of normal ciliary function in mammals is responsible for cystic and noncystic pathology in the kidney, liver, brain, and pancreas, as well as severe developmental patterning abnormalities. In addition, the localization of proteins involved in rare human disorders such as Bardet-Biedl syndrome has suggested that cilia-related dysfunction may play a role in modern human epidemics such as hypertension, obesity, and diabetes. Although we have made great advances in demonstrating the importance of cilia over the past decade, the physiological role that this organelle plays in most tissues remains elusive. Research focused on addressing this issue will be of critical importance for a further understanding of how ciliary dysfunction can lead to such severe Disease and developmental pathologies.
Roan Louw - One of the best experts on this subject based on the ideXlab platform.
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Novel mitochondrial and cytosolic purification pipeline for compartment-specific metabolomics in Mammalian Disease model tissues
Metabolomics, 2020Co-Authors: Gunter Van Der Walt, Roan LouwAbstract:Introduction Mitochondria represent an important milieu for studying the pathogenesis of several major Diseases. The need for organelle-level metabolic resolution exists, as mitochondrial/cytosolic metabolites are often diluted beyond detection limits in complex samples. Compartment-specific studies are still hindered by the lack of efficient, cost-effective fractioning methods—applicable to laboratories of all financial/analytical standing. Objectives We established a novel mitochondrial/cytosolic purification pipeline for complimentary GC-TOF–MS and ^1H-NMR metabolomics using robust, commercially available fractionation strategies. Methods Magnetic based mitochondria isolation kits (MACS) were adapted for this purpose, accompanied by cytosolic filtering. Yield was assessed through the percentage recovery of citrate synthase (CS; a mitochondrial marker), purity by immunoblotting against compartment-specific proteins and integrity interrogated through the respiratory coupling ratio (RCR). The effects of the kit-based buffers on MS/NMR analyses of pure metabolite standards were evaluated. Finally, biological applicability to Mammalian Disease models was shown using Ndufs4 mouse brain tissue. Results With minor modifications, MACS produced around 60% more mitochondria compared to a differential centrifugation method. Less than 15% of lysosomal LAMP-2 protein was found in the MACS isolates, confirming relative purity—while RCR’s above 6 indicate sufficient mitochondrial integrity. The filtering approach effectively depleted mitochondria from the cytosolic fraction, as indicated by negligible Hsp60 and CS levels. Our GC–MS pilot yielded 60–70 features per fraction, while NMR analyses could quantify 6–10 of the most abundant compounds in each fraction. Conclusion This study provides a simple and flexible solution for mitochondrial and cytosolic metabolomics in animal model tissues, towards large-scale application of such methodologies in Disease research.
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Novel mitochondrial and cytosolic purification pipeline for compartment-specific metabolomics in Mammalian Disease model tissues
Metabolomics : Official journal of the Metabolomic Society, 2020Co-Authors: Gunter Van Der Walt, Roan LouwAbstract:Mitochondria represent an important milieu for studying the pathogenesis of several major Diseases. The need for organelle-level metabolic resolution exists, as mitochondrial/cytosolic metabolites are often diluted beyond detection limits in complex samples. Compartment-specific studies are still hindered by the lack of efficient, cost-effective fractioning methods—applicable to laboratories of all financial/analytical standing. We established a novel mitochondrial/cytosolic purification pipeline for complimentary GC-TOF–MS and 1H-NMR metabolomics using robust, commercially available fractionation strategies. Magnetic based mitochondria isolation kits (MACS) were adapted for this purpose, accompanied by cytosolic filtering. Yield was assessed through the percentage recovery of citrate synthase (CS; a mitochondrial marker), purity by immunoblotting against compartment-specific proteins and integrity interrogated through the respiratory coupling ratio (RCR). The effects of the kit-based buffers on MS/NMR analyses of pure metabolite standards were evaluated. Finally, biological applicability to Mammalian Disease models was shown using Ndufs4 mouse brain tissue. With minor modifications, MACS produced around 60% more mitochondria compared to a differential centrifugation method. Less than 15% of lysosomal LAMP-2 protein was found in the MACS isolates, confirming relative purity—while RCR’s above 6 indicate sufficient mitochondrial integrity. The filtering approach effectively depleted mitochondria from the cytosolic fraction, as indicated by negligible Hsp60 and CS levels. Our GC–MS pilot yielded 60–70 features per fraction, while NMR analyses could quantify 6–10 of the most abundant compounds in each fraction. This study provides a simple and flexible solution for mitochondrial and cytosolic metabolomics in animal model tissues, towards large-scale application of such methodologies in Disease research.
Raymond F. Robledo - One of the best experts on this subject based on the ideXlab platform.
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strain specific hyperkyphosis and megaesophagus in add1 null mice
Genesis, 2012Co-Authors: Raymond F. Robledo, Kevin L. Seburn, Anthony Nicholson, Luanne L. PetersAbstract:The three adducin proteins (α, β, and γ) share extensive sequence, structural, and functional homology. Heterodimers of α- and β-adducin are vital components of the red cell membrane skeleton, which is required to maintain red cell elasticity and structural integrity. In addition to anemia, targeted deletion of the α-adducin gene (Add1) reveals unexpected, strain-dependentnon-erythroid phenotypes. On an inbred 129 genetic background, Add1 null mice show abnormal inward curvature of the cervicothoracic spine with complete penetrance. More surprisingly, a subset of 129-Add1 null mice develop severe megaesophagus, while examination of peripheral nerves reveals a reduced number of axons in 129-Add1 null mice at four months of age. These unforeseen phenotypes, described here, reveal new functions for adducin and provide new models of Mammalian Disease. genesis 50:882–891, 2012. © 2012 Wiley Periodicals, Inc.
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Strain-specific hyperkyphosis and megaesophagus in Add1 null mice.
Genesis (New York N.Y. : 2000), 2012Co-Authors: Raymond F. Robledo, Kevin L. Seburn, Anthony Nicholson, Luanne L. PetersAbstract:The three adducin proteins (α, β, and γ) share extensive sequence, structural, and functional homology. Heterodimers of α- and β-adducin are vital components of the red cell membrane skeleton, which is required to maintain red cell elasticity and structural integrity. In addition to anemia, targeted deletion of the α-adducin gene (Add1) reveals unexpected, strain-dependent non-erythroid phenotypes. On an inbred 129 genetic background, Add1 null mice show abnormal inward curvature of the cervicothoracic spine with complete penetrance. More surprisingly, a subset of 129-Add1 null mice develop severe megaesophagus, while examination of peripheral nerves reveals a reduced number of axons in 129-Add1 null mice at four months of age. These unforeseen phenotypes, described here, reveal new functions for adducin and provide new models of Mammalian Disease.
James R Davenport - One of the best experts on this subject based on the ideXlab platform.
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an incredible decade for the primary cilium a look at a once forgotten organelle
American Journal of Physiology-renal Physiology, 2005Co-Authors: James R Davenport, Bradley K YoderAbstract:Since the discovery that numerous proteins involved in Mammalian Disease localize to the basal bodies and cilia, these organelles have emerged from relative obscurity to the center of intense resea...
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an incredible decade for the primary cilium a look at a once forgotten organelle
American Journal of Physiology-renal Physiology, 2005Co-Authors: James R Davenport, Bradley K YoderAbstract:Since the discovery that numerous proteins involved in Mammalian Disease localize to the basal bodies and cilia, these organelles have emerged from relative obscurity to the center of intense research efforts in an expanding number of Disease- and developmental-related fields. Our understanding of the association between cilia and human Disease has benefited substantially from the use of lower organisms such as Chlamydomonas and Caenorhabditis elegans and the availability of murine models and cell culture. These research endeavors led to the discovery that loss of normal ciliary function in mammals is responsible for cystic and noncystic pathology in the kidney, liver, brain, and pancreas, as well as severe developmental patterning abnormalities. In addition, the localization of proteins involved in rare human disorders such as Bardet-Biedl syndrome has suggested that cilia-related dysfunction may play a role in modern human epidemics such as hypertension, obesity, and diabetes. Although we have made great advances in demonstrating the importance of cilia over the past decade, the physiological role that this organelle plays in most tissues remains elusive. Research focused on addressing this issue will be of critical importance for a further understanding of how ciliary dysfunction can lead to such severe Disease and developmental pathologies.
