Установлено существование оптимального значения теплопроводности, при котором достигается наиболее равномерное распределение модуля температурного градиента на фронте кристаллизации

Andre R A Marques

Andries Kalsbeek

Cindy van Roomen

Daniela Herrera Moro Chao

Elly M Hol

Ewout Foppen

Hermen S Overkleeft

Jan Aten

Johannes M F G Aerts

Marco van Eijk

Maria C Renner

Marie Orre

Martina Moeton

Roelof Ottenhoff

Rolf G Boot

Willem Kamphuis

Wouter W Kallemeijn

Технология и конструирование в электронной аппаратуре

PubMed

Gaucher disease is characterized by lysosomal accumulation of glucosylceramide due to deficient activity of lysosomal glucocerebrosidase (GBA). In cells, glucosylceramide is also degraded outside lysosomes by the enzyme glucosylceramidase 2 (GBA2) of which inherited deficiency is associated with ataxias. The interest in GBA and glucosylceramide metabolism in the brain has grown following the notion that mutations in the GBA gene impose a risk factor for motor disorders such as alpha-synucleinopathies. We earlier developed a beta-glucopyranosylconfigured cyclophellitol-epoxide type activity based probe (ABP) allowing in vivo and in vitro visualization of activemolecules of GBA with high spatial resolution. Labeling occurs through covalent linkage of the ABP to the catalytic nucleophile residue in the enzyme pocket. Here, we describe a method to visualize active GBA molecules in rat brain slices using in vivo labeling. Brain areas related to motor control, like the basal ganglia and motor related structures in the brainstem, show a high content of active GBA. We also developed a beta-glucopyranosyl cyclophellitol-aziridine ABP allowing in situ labeling of GBA2. Labeled GBA2 in brain areas can be identified and quantified upon gel electrophoresis. The distribution of active GBA2 markedly differs from that of GBA, being highest in the cerebellar cortex. The histological findings with ABP labeling were confirmed by biochemical analysis of isolated brain areas. In conclusion, ABPs offer sensitive tools to visualize active GBA and to study the distribution of GBA2 in the brain and thus may find application to establish the role of these enzymes in neurodegenerative disease conditions such as alpha-synucleinopathies and cerebellar ataxia

Chao, Daniela Herrera Moro

Kallemeijn, Wouter W.

Marques, Andre R. A.

Orre, Marie

Ottenhoff, Roelof

van Roomen, Cindy

Foppen, Ewout

Renner, Maria C.

Moeton, Martina

van Eijk, Marco

Boot, Rolf G.

Kamphuis, Willem

Hol, Elly M.

Aten, Jan

Overkleeft, Hermen S.

Kalsbeek, Andries

Aerts, Johannes M. F. G.

NARCIS 

Visualization of Active Glucocerebrosidase in Rodent Brain with High Spatial Resolution following In Situ Labeling with Fluorescent Activity Based Probes

Ковтун, Г.П.

Кравченко, А.И.

Кондрик, А.И.

Наукова електронна бібліотека періодичних видань НАН України (Vernadsky National Library of Ukraine)

Температурное поле в кристалле иттрий-алюминиевого граната при двухстадийном выращивании

Gaucher disease is characterized by lysosomal accumulation of glucosylceramide due to deficient activity of lysosomal glucocerebrosidase (GBA). In cells, glucosylceramide is also degraded outside lysosomes by the enzyme glucosylceramidase 2 (GBA2) of which inherited deficiency is associated with ataxias. The interest in GBA and glucosylceramide metabolism in the brain has grown following the notion that mutations in the GBA gene impose a risk factor for motor disorders such as α-synucleinopathies. We earlier developed a β-glucopyranosyl-configured cyclophellitol-epoxide type activity based probe (ABP) allowing in vivo and in vitro visualization of active molecules of GBA with high spatial resolution. Labeling occurs through covalent linkage of the ABP to the catalytic nucleophile residue in the enzyme pocket. Here, we describe a method to visualize active GBA molecules in rat brain slices using in vivo labeling. Brain areas related to motor control, like the basal ganglia and motor related structures in the brainstem, show a high content of active GBA. We also developed a β-glucopyranosyl cyclophellitol-aziridine ABP allowing in situ labeling of GBA2. Labeled GBA2 in brain areas can be identified and quantified upon gel electrophoresis. The distribution of active GBA2 markedly differs from that of GBA, being highest in the cerebellar cortex. The histological findings with ABP labeling were confirmed by biochemical analysis of isolated brain areas. In conclusion, ABPs offer sensitive tools to visualize active GBA and to study the distribution of GBA2 in the brain and thus may find application to establish the role of these enzymes in neurodegenerative disease conditions such as α-synucleinopathies and cerebellar ataxia

Directory of Open Access Journals

PLoS ONE

Visualization of Active Glucocerebrosidase in Rodent Brain with High Spatial Resolution following In Situ Labeling with Fluorescent Activity Based Probes.

<div>Gaucher disease is characterized by lysosomal accumulation of glucosylceramide due to deficient activity of lysosomal glucocerebrosidase (GBA). In cells, glucosylceramide is also degraded outside lysosomes by the enzyme glucosylceramidase 2 (GBA2) of which inherited deficiency is associated with ataxias. The interest in GBA and glucosylceramide metabolism in the brain has grown following the notion that mutations in the GBA gene impose a risk factor for motor disorders such as α-synucleinopathies. We earlier developed a β-glucopyranosyl-configured cyclophellitol-epoxide type activity based probe (ABP) allowing in vivo and in vitro visualization of active molecules of GBA with high spatial resolution. Labeling occurs through covalent linkage of the ABP to the catalytic nucleophile residue in the enzyme pocket. Here, we describe a method to visualize active GBA molecules in rat brain slices using in vivo labeling. Brain areas related to motor control, like the basal ganglia and motor related structures in the brainstem, show a high content of active GBA. We also developed a β-glucopyranosyl cyclophellitol-aziridine ABP allowing in situ labeling of GBA2. Labeled GBA2 in brain areas can be identified and quantified upon gel electrophoresis. The distribution of active GBA2 markedly differs from that of GBA, being highest in the cerebellar cortex. The histological findings with ABP labeling were confirmed by biochemical analysis of isolated brain areas. In conclusion, ABPs offer sensitive tools to visualize active GBA and to study the distribution of GBA2 in the brain and thus may find application to establish the role of these enzymes in neurodegenerative disease conditions such as α-synucleinopathies and cerebellar ataxia.</div

Daniela Herrera Moro Chao (801325)

Wouter W. Kallemeijn (801326)

Andre R. A. Marques (5665474)

Marie Orre (142600)

Roelof Ottenhoff (128566)

Cindy van Roomen (801327)

Ewout Foppen (95823)

Maria C. Renner (801328)

Martina Moeton (142557)

Marco van Eijk (128570)

Rolf G. Boot (783479)

Willem Kamphuis (110003)

Elly M. Hol (82147)

Jan Aten (128574)

Hermen S. Overkleeft (265766)

Andries Kalsbeek (95822)

Johannes M. F. G. Aerts (128594)

FigShare

Visualization of Active Glucocerebrosidase in Rodent Brain with High Spatial Resolution following In Situ Labeling with Fluorescent Activity Based Probes

Utrecht University Repository

Herrera Moro Chao, Daniela

Kallemeijn, Wouter W

Marques, Andre R A

Renner, Maria C

Boot, Rolf G

Hol, Elly M

Overkleeft, Hermen S

Aerts, Johannes M F G

Gaucher disease is characterized by lysosomal accumulation of glucosylceramide due to deficient activity of lysosomal glucocerebrosidase (GBA). In cells, glucosylceramide is also degraded outside lysosomes by the enzyme glucosylceramidase 2 (GBA2) of which inherited deficiency is associated with ataxias. The interest in GBA and glucosylceramide metabolism in the brain has grown following the notion that mutations in the GBA gene impose a risk factor for motor disorders such as α-synucleinopathies. We earlier developed a β-glucopyranosyl-configured cyclophellitol-epoxide type activity based probe (ABP) allowing in vivo and in vitro visualization of active molecules of GBA with high spatial resolution. Labeling occurs through covalent linkage of the ABP to the catalytic nucleophile residue in the enzyme pocket. Here, we describe a method to visualize active GBA molecules in rat brain slices using in vivo labeling. Brain areas related to motor control, like the basal ganglia and motor related structures in the brainstem, show a high content of active GBA. We also developed a β-glucopyranosyl cyclophellitol-aziridine ABP allowing in situ labeling of GBA2. Labeled GBA2 in brain areas can be identified and quantified upon gel electrophoresis. The distribution of active GBA2 markedly differs from that of GBA, being highest in the cerebellar cortex. The histological findings with ABP labeling were confirmed by biochemical analysis of isolated brain areas. In conclusion, ABPs offer sensitive tools to visualize active GBA and to study the distribution of GBA2 in the brain and thus may find application to establish the role of these enzymes in neurodegenerative disease conditions such as α-synucleinopathies and cerebellar ataxi

Температурное поле в кристалле иттрий-алюминиевого граната при двухстадийном выращивании

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Наукова електронна бібліотека періодичних видань НАН України (Vernadsky National Library of Ukraine)

Directory of Open Access Journals

FigShare

Utrecht University Repository

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