The Experts below are selected from a list of 603 Experts worldwide ranked by ideXlab platform
Katja M Kanninen - One of the best experts on this subject based on the ideXlab platform.
-
Metals and neurodegeneration: Restoring the balance
Frontiers Media SA, 2016Co-Authors: Peter J. Crouch, Katja M Kanninen, Anthony R. WhiteAbstract:Biometals such as copper, zinc and iron have key biological functions, however, aberrant metabolism can lead to detrimental effects on cell function and survival. These Biometals have important roles in the brain, driving cellular respiration, antioxidant activity, intracellular signaling and many additional structural and enzymatic functions. There is now considerable evidence that abnormal biometal homeostasis is a key feature of many neurodegenerative diseases and may have an important role in the onset and progression of disorders such as Alzheimer’s, Parkinson’s, prion and motor neuron diseases. Recent studies also support biometal roles in a number of less common neurodegenerative disorders. The role of Biometals in a growing list of brain disorders is supported by evidence from a wide range of sources including molecular genetics, biochemical studies and biometal imaging. These studies have spurred a growing interest in understanding the role of Biometals in brain function and disease as well as the development of therapeutic approaches that may be able to restore the altered biometal chemistry of the brain. These approaches range from genetic manipulation of biometal transport to chelation of excess metals or delivery of metals where levels are deficient. A number of these approaches are offering promising results in cellular and animal models of neurodegeneration with successful translation to pre-clinical and clinical trials. At a time of aging populations and slow progress in development of neurotherapeutics to treat age-related neurodegenerative diseases, there is now a critical need to further our understanding of Biometals in neurodegeneration. This issue covers a broad range of topics related to Biometals and their role in neurodegeneration. It is hoped that this will inspire greater discussion and exchange of ideas in this crucial area of research and lead to positive outcomes for sufferers of these neurodegenerative diseases
-
altered biometal homeostasis is associated with cln6 mrna loss in mouse neuronal ceroid lipofuscinosis
Biology Open, 2013Co-Authors: Alexandra Grubman, Aphrodite Caragounis, Clare Duncan, Grace E Lidgerwood, Irene Volitakis, Sarah J. Parker, Katja M Kanninen, George GanioAbstract:Neuronal ceroid lipofuscinoses, the most common fatal childhood neurodegenerative illnesses, share many features with more prevalent neurodegenerative diseases. Neuronal ceroid lipofuscinoses are caused by mutations in CLN genes. CLN6 encodes a transmembrane endoplasmic reticulum protein with no known function. We characterized the behavioural phenotype of spontaneous mutant mice modeling CLN6 disease, and demonstrate progressive motor and visual decline and reduced lifespan in these mice, consistent with symptoms observed in neuronal ceroid lipofuscinosis patients. Alterations to biometal homeostasis are known to play a critical role in pathology in Alzheimer's, Parkinson's, Huntington's and motor neuron diseases. We have previously shown accumulation of the Biometals, zinc, copper, manganese and cobalt, in CLN6 Merino and South Hampshire sheep at the age of symptom onset. Here we determine the physiological and disease-associated expression of CLN6, demonstrating regional CLN6 transcript loss, and concurrent accumulation of the same Biometals in the CNS and the heart of presymptomatic CLN6 mice. Furthermore, increased expression of the ER/Golgi-localized cation transporter protein, Zip7, was detected in cerebellar Purkinje cells and whole brain fractions. Purkinje cells not only control motor function, an early symptomatic change in the CLN6 mice, but also display prominent neuropathological changes in mouse models and patients with different forms of neuronal ceroid lipofuscinoses. Whole brain fractionation analysis revealed biometal accumulation in fractions expressing markers for ER, Golgi, endosomes and lysosomes of CLN6 brains. These data are consistent with a link between CLN6 expression and biometal homeostasis in CLN6 disease, and provide further support for altered cation transporter regulation as a key factor in neurodegeneration.
-
altered biometal homeostasis is associated with cln6 mrna loss in mouse neuronal ceroid lipofuscinosis
Biology Open, 2013Co-Authors: Alexandra Grubman, Aphrodite Caragounis, Clare Duncan, Grace E Lidgerwood, Irene Volitakis, Sarah J. Parker, Katja M Kanninen, George GanioAbstract:Neuronal ceroid lipofuscinoses, the most common fatal childhood neurodegenerative illnesses, share many features with more prevalent neurodegenerative diseases. Neuronal ceroid lipofuscinoses are caused by mutations in CLN genes. CLN6 encodes a transmembrane endoplasmic reticulum protein with no known function. We characterized the behavioural phenotype of spontaneous mutant mice modeling CLN6 disease, and demonstrate progressive motor and visual decline and reduced lifespan in these mice, consistent with symptoms observed in neuronal ceroid lipofuscinosis patients. Alterations to biometal homeostasis are known to play a critical role in pathology in Alzheimer's, Parkinson's, Huntington's and motor neuron diseases. We have previously shown accumulation of the Biometals, zinc, copper, manganese and cobalt, in CLN6 Merino and South Hampshire sheep at the age of symptom onset. Here we determine the physiological and disease-associated expression of CLN6, demonstrating regional CLN6 transcript loss, and concurrent accumulation of the same Biometals in the CNS and the heart of presymptomatic CLN6 mice. Furthermore, increased expression of the ER/Golgi-localized cation transporter protein, Zip7, was detected in cerebellar Purkinje cells and whole brain fractions. Purkinje cells not only control motor function, an early symptomatic change in the CLN6 mice, but also display prominent neuropathological changes in mouse models and patients with different forms of neuronal ceroid lipofuscinoses. Whole brain fractionation analysis revealed biometal accumulation in fractions expressing markers for ER, Golgi, endosomes and lysosomes of CLN6 brains. These data are consistent with a link between CLN6 expression and biometal homeostasis in CLN6 disease, and provide further support for altered cation transporter regulation as a key factor in neurodegeneration.
-
Biometals in rare neurodegenerative disorders of childhood
Frontiers in Aging Neuroscience, 2013Co-Authors: Sarah J. Parker, Katja M Kanninen, Anthony R. White, Jari KoistinahoAbstract:Copper, iron and zinc are just three of the main Biometals critical for correct functioning of the central nervous system. They have diverse roles in many functional processes including but not limited to enzyme catalysis, protein stabilisation, and energy production. The range of metal concentrations within the body is tightly regulated and when the balance is perturbed, debilitating effects ensue. Homeostasis of brain Biometals is mainly controlled by various metal transporters and metal sequestering proteins. The biological roles of Biometals are vastly reviewed in the literature with a large focus on the connection to neurological conditions associated with ageing. Biometals are also implicated in a variety of debilitating inherited childhood disorders, some of which arise soon following birth or as the child progresses into early adulthood. This review acts to highlight what we know about Biometals in childhood neurological disorders such as Wilson’s disease, Menkes disease, neuronal ceroid lipofuscinoses and neurodegeneration with brain iron accumulation. Also discussed are some of the animal models available to determine the pathological mechanisms in these childhood disorders, which we hope will aid in our understanding of the role of Biometals in disease and in attaining possible therapeutics in the future.
Agamemnon Koutsospyros - One of the best experts on this subject based on the ideXlab platform.
-
Kinetics of Reductive Degradation of 2,4-dinitroanisole (DNAN) Using Mg-Based Bimetals
Environmental Processes, 2019Co-Authors: Andrew Mai, Benjamin Smolinski, Emese Hadnagy, Stanley Menacherry, Agamemnon KoutsospyrosAbstract:Technology advancements and modern use of explosives have led to the development of insensitive munitions such as 2,4-dinitroanisole (DNAN). Treatment systems using zero-valent iron (ZVI) and Fe-based bimetals are well-known, however, Mg-based bimetals can be advantageous over iron because of the more negative reduction potential and relative insensitivity to pH conditions. This work reports on the use of ZVMg and Mg-bimetals (Mg/Cu, Mg/Ni, Mg/Zn) to treat pure compound aqueous solutions and wastewater containing DNAN. Kinetic experiments were carried out in bench-scale batch reactors at unadjusted initial pH, 0.5% solids-to-liquid ratio (S/L), and 10:1 Mg to catalytic metal ratio. The results, modelled with a pseudo-first order kinetic expression, are used to determine reaction rate constants via nonlinear regression. For pure DNAN aqueous solutions, the pseudo-first order kinetic rate constants are 0.119, 0.102, 0.020, and 0.009 min^−1 for Mg/Cu, Mg/Zn, Mg/Ni, and ZVMg, respectively. Reaction rate constants for DNAN wastewater are 0.114, 0.046, and 0.021 min^−1 for Mg/Cu, Mg/Zn and Mg/Ni, respectively. Parametric studies investigated the impact of catalytic metal, reagent dose, and initial pH on DNAN degradation. Reagent dose levels tested were 0.25, 0.50 and 0.75% S/L. Initial pH, lowered with acetic acid (pH range 3.3–4.0), significantly enhanced reaction rates of all bimetal pairs and ZVMg yielding half-lives between 0.7–1.4 min. The bimetal pair showing the fastest kinetics at unadjusted initial pH, Mg/Cu, was characterized in constant temperature experiments. Under identical conditions (unadjusted initial pH, 0.5% S/L, 10:1 Mg: Cu), the activation energy of DNAN degradation by Mg/Cu is 8.47 kJ/mol.
-
Characterization of Mg-based bimetal treatment of insensitive munition 2,4-dinitroanisole
Environmental Science and Pollution Research, 2018Co-Authors: Emese Hadnagy, Benjamin Smolinski, Andrew Mai, Washington Braida, Agamemnon KoutsospyrosAbstract:The manufacturing of insensitive munition 2,4-dinitroanisole (DNAN) generates waste streams that require treatment. DNAN has been treated previously with zero-valent iron (ZVI) and Fe-based bimetals. Use of Mg-based bimetals offers certain advantages including potential higher reactivity and relative insensitivity to pH conditions. This work reports preliminary findings of DNAN degradation by three Mg-based bimetals: Mg/Cu, Mg/Ni, and Mg/Zn. Treatment of DNAN by all three bimetals is highly effective in aqueous solutions (> 89% removal) and wastewater (> 91% removal) in comparison with treatment solely with zero-valent magnesium (ZVMg; 35% removal). Investigation of reaction byproducts supports a partial degradation pathway involving reduction of the ortho or para nitro to amino group, leading to 2-amino-4-nitroanisole (2-ANAN) and 4-amino-2-nitroanisole (4-ANAN). Further reduction of the second nitro group leads to 2,4-diaminoanisole (DAAN). These byproducts are detected in small quantities in the aqueous phase. Carbon mass balance analysis suggests near-complete closure (91%) with 12.4 and 78.4% of the total organic carbon (TOC) distributed in the aqueous and mineral bimetal phases, respectively. Post-treatment surface mineral phase analysis indicates Mg(OH)2 as the main oxidized species; oxide formation does not appear to impair treatment.
Sarah J. Parker - One of the best experts on this subject based on the ideXlab platform.
-
altered biometal homeostasis is associated with cln6 mrna loss in mouse neuronal ceroid lipofuscinosis
Biology Open, 2013Co-Authors: Alexandra Grubman, Aphrodite Caragounis, Clare Duncan, Grace E Lidgerwood, Irene Volitakis, Sarah J. Parker, Katja M Kanninen, George GanioAbstract:Neuronal ceroid lipofuscinoses, the most common fatal childhood neurodegenerative illnesses, share many features with more prevalent neurodegenerative diseases. Neuronal ceroid lipofuscinoses are caused by mutations in CLN genes. CLN6 encodes a transmembrane endoplasmic reticulum protein with no known function. We characterized the behavioural phenotype of spontaneous mutant mice modeling CLN6 disease, and demonstrate progressive motor and visual decline and reduced lifespan in these mice, consistent with symptoms observed in neuronal ceroid lipofuscinosis patients. Alterations to biometal homeostasis are known to play a critical role in pathology in Alzheimer's, Parkinson's, Huntington's and motor neuron diseases. We have previously shown accumulation of the Biometals, zinc, copper, manganese and cobalt, in CLN6 Merino and South Hampshire sheep at the age of symptom onset. Here we determine the physiological and disease-associated expression of CLN6, demonstrating regional CLN6 transcript loss, and concurrent accumulation of the same Biometals in the CNS and the heart of presymptomatic CLN6 mice. Furthermore, increased expression of the ER/Golgi-localized cation transporter protein, Zip7, was detected in cerebellar Purkinje cells and whole brain fractions. Purkinje cells not only control motor function, an early symptomatic change in the CLN6 mice, but also display prominent neuropathological changes in mouse models and patients with different forms of neuronal ceroid lipofuscinoses. Whole brain fractionation analysis revealed biometal accumulation in fractions expressing markers for ER, Golgi, endosomes and lysosomes of CLN6 brains. These data are consistent with a link between CLN6 expression and biometal homeostasis in CLN6 disease, and provide further support for altered cation transporter regulation as a key factor in neurodegeneration.
-
altered biometal homeostasis is associated with cln6 mrna loss in mouse neuronal ceroid lipofuscinosis
Biology Open, 2013Co-Authors: Alexandra Grubman, Aphrodite Caragounis, Clare Duncan, Grace E Lidgerwood, Irene Volitakis, Sarah J. Parker, Katja M Kanninen, George GanioAbstract:Neuronal ceroid lipofuscinoses, the most common fatal childhood neurodegenerative illnesses, share many features with more prevalent neurodegenerative diseases. Neuronal ceroid lipofuscinoses are caused by mutations in CLN genes. CLN6 encodes a transmembrane endoplasmic reticulum protein with no known function. We characterized the behavioural phenotype of spontaneous mutant mice modeling CLN6 disease, and demonstrate progressive motor and visual decline and reduced lifespan in these mice, consistent with symptoms observed in neuronal ceroid lipofuscinosis patients. Alterations to biometal homeostasis are known to play a critical role in pathology in Alzheimer's, Parkinson's, Huntington's and motor neuron diseases. We have previously shown accumulation of the Biometals, zinc, copper, manganese and cobalt, in CLN6 Merino and South Hampshire sheep at the age of symptom onset. Here we determine the physiological and disease-associated expression of CLN6, demonstrating regional CLN6 transcript loss, and concurrent accumulation of the same Biometals in the CNS and the heart of presymptomatic CLN6 mice. Furthermore, increased expression of the ER/Golgi-localized cation transporter protein, Zip7, was detected in cerebellar Purkinje cells and whole brain fractions. Purkinje cells not only control motor function, an early symptomatic change in the CLN6 mice, but also display prominent neuropathological changes in mouse models and patients with different forms of neuronal ceroid lipofuscinoses. Whole brain fractionation analysis revealed biometal accumulation in fractions expressing markers for ER, Golgi, endosomes and lysosomes of CLN6 brains. These data are consistent with a link between CLN6 expression and biometal homeostasis in CLN6 disease, and provide further support for altered cation transporter regulation as a key factor in neurodegeneration.
-
Biometals in rare neurodegenerative disorders of childhood
Frontiers in Aging Neuroscience, 2013Co-Authors: Sarah J. Parker, Katja M Kanninen, Anthony R. White, Jari KoistinahoAbstract:Copper, iron and zinc are just three of the main Biometals critical for correct functioning of the central nervous system. They have diverse roles in many functional processes including but not limited to enzyme catalysis, protein stabilisation, and energy production. The range of metal concentrations within the body is tightly regulated and when the balance is perturbed, debilitating effects ensue. Homeostasis of brain Biometals is mainly controlled by various metal transporters and metal sequestering proteins. The biological roles of Biometals are vastly reviewed in the literature with a large focus on the connection to neurological conditions associated with ageing. Biometals are also implicated in a variety of debilitating inherited childhood disorders, some of which arise soon following birth or as the child progresses into early adulthood. This review acts to highlight what we know about Biometals in childhood neurological disorders such as Wilson’s disease, Menkes disease, neuronal ceroid lipofuscinoses and neurodegeneration with brain iron accumulation. Also discussed are some of the animal models available to determine the pathological mechanisms in these childhood disorders, which we hope will aid in our understanding of the role of Biometals in disease and in attaining possible therapeutics in the future.
Emese Hadnagy - One of the best experts on this subject based on the ideXlab platform.
-
Kinetics of Reductive Degradation of 2,4-dinitroanisole (DNAN) Using Mg-Based Bimetals
Environmental Processes, 2019Co-Authors: Andrew Mai, Benjamin Smolinski, Emese Hadnagy, Stanley Menacherry, Agamemnon KoutsospyrosAbstract:Technology advancements and modern use of explosives have led to the development of insensitive munitions such as 2,4-dinitroanisole (DNAN). Treatment systems using zero-valent iron (ZVI) and Fe-based bimetals are well-known, however, Mg-based bimetals can be advantageous over iron because of the more negative reduction potential and relative insensitivity to pH conditions. This work reports on the use of ZVMg and Mg-bimetals (Mg/Cu, Mg/Ni, Mg/Zn) to treat pure compound aqueous solutions and wastewater containing DNAN. Kinetic experiments were carried out in bench-scale batch reactors at unadjusted initial pH, 0.5% solids-to-liquid ratio (S/L), and 10:1 Mg to catalytic metal ratio. The results, modelled with a pseudo-first order kinetic expression, are used to determine reaction rate constants via nonlinear regression. For pure DNAN aqueous solutions, the pseudo-first order kinetic rate constants are 0.119, 0.102, 0.020, and 0.009 min^−1 for Mg/Cu, Mg/Zn, Mg/Ni, and ZVMg, respectively. Reaction rate constants for DNAN wastewater are 0.114, 0.046, and 0.021 min^−1 for Mg/Cu, Mg/Zn and Mg/Ni, respectively. Parametric studies investigated the impact of catalytic metal, reagent dose, and initial pH on DNAN degradation. Reagent dose levels tested were 0.25, 0.50 and 0.75% S/L. Initial pH, lowered with acetic acid (pH range 3.3–4.0), significantly enhanced reaction rates of all bimetal pairs and ZVMg yielding half-lives between 0.7–1.4 min. The bimetal pair showing the fastest kinetics at unadjusted initial pH, Mg/Cu, was characterized in constant temperature experiments. Under identical conditions (unadjusted initial pH, 0.5% S/L, 10:1 Mg: Cu), the activation energy of DNAN degradation by Mg/Cu is 8.47 kJ/mol.
-
Characterization of Mg-based bimetal treatment of insensitive munition 2,4-dinitroanisole
Environmental Science and Pollution Research, 2018Co-Authors: Emese Hadnagy, Benjamin Smolinski, Andrew Mai, Washington Braida, Agamemnon KoutsospyrosAbstract:The manufacturing of insensitive munition 2,4-dinitroanisole (DNAN) generates waste streams that require treatment. DNAN has been treated previously with zero-valent iron (ZVI) and Fe-based bimetals. Use of Mg-based bimetals offers certain advantages including potential higher reactivity and relative insensitivity to pH conditions. This work reports preliminary findings of DNAN degradation by three Mg-based bimetals: Mg/Cu, Mg/Ni, and Mg/Zn. Treatment of DNAN by all three bimetals is highly effective in aqueous solutions (> 89% removal) and wastewater (> 91% removal) in comparison with treatment solely with zero-valent magnesium (ZVMg; 35% removal). Investigation of reaction byproducts supports a partial degradation pathway involving reduction of the ortho or para nitro to amino group, leading to 2-amino-4-nitroanisole (2-ANAN) and 4-amino-2-nitroanisole (4-ANAN). Further reduction of the second nitro group leads to 2,4-diaminoanisole (DAAN). These byproducts are detected in small quantities in the aqueous phase. Carbon mass balance analysis suggests near-complete closure (91%) with 12.4 and 78.4% of the total organic carbon (TOC) distributed in the aqueous and mineral bimetal phases, respectively. Post-treatment surface mineral phase analysis indicates Mg(OH)2 as the main oxidized species; oxide formation does not appear to impair treatment.
Majid Etminanbakhsh - One of the best experts on this subject based on the ideXlab platform.
-
microstructural evolution and interfacial diffusion during heat treatment of hastelloy stainless steel bimetals
Journal of Alloys and Compounds, 2017Co-Authors: O Hedayati, N Korei, Mahdieh Adeli, Majid EtminanbakhshAbstract:Abstract Hastelloy/stainless steel bimetals have found wide applications in chemical, petrochemical, and marine applications. In this study, the effect of short-time exposure to elevated temperatures on an explosively-welded Hastelloy/stainless steel bimetal was investigated. Samples prepared from the bimetal were heat-treated at 800 °C, 900 °C, 1000 °C, and 1100 °C for times up to 3 h. Microscopic examination of the interface showed no variations in the microstructure after heating at 800 °C even at longer times. At 900 °C and 1000 °C, the interdiffusion of atoms became significant; arrays of carbide precipitates appeared in the microstructure on the Hastelloy side which seemed to coarsen with increase in temperature and time. At temperatures as high as 1100 °C, 30min of heat treatment resulted in the formation of a significant number of coarse carbide precipitates on the Hastelloy side, as well as a line of carbides on the steel side. It was concluded that these bimetals may not be suitable for application in service temperatures higher than 800 °C. Even short-time exposure to elevated temperatures can develop coarse carbide networks at the interface, rendering the weld unreliable and susceptible to failure.
-
microstructural evolution and interfacial diffusion during heat treatment of hastelloy stainless steel bimetals
Journal of Alloys and Compounds, 2017Co-Authors: O Hedayati, N Korei, Mahdieh Adeli, Majid EtminanbakhshAbstract:Abstract Hastelloy/stainless steel bimetals have found wide applications in chemical, petrochemical, and marine applications. In this study, the effect of short-time exposure to elevated temperatures on an explosively-welded Hastelloy/stainless steel bimetal was investigated. Samples prepared from the bimetal were heat-treated at 800 °C, 900 °C, 1000 °C, and 1100 °C for times up to 3 h. Microscopic examination of the interface showed no variations in the microstructure after heating at 800 °C even at longer times. At 900 °C and 1000 °C, the interdiffusion of atoms became significant; arrays of carbide precipitates appeared in the microstructure on the Hastelloy side which seemed to coarsen with increase in temperature and time. At temperatures as high as 1100 °C, 30min of heat treatment resulted in the formation of a significant number of coarse carbide precipitates on the Hastelloy side, as well as a line of carbides on the steel side. It was concluded that these bimetals may not be suitable for application in service temperatures higher than 800 °C. Even short-time exposure to elevated temperatures can develop coarse carbide networks at the interface, rendering the weld unreliable and susceptible to failure.