161 research outputs found
Disulfide cross-links in the interaction of a cataract-linked αA-crystallin mutant with ÎČB1-crystallin
AbstractA number of αA-crystallin mutants are associated with hereditary cataract including cysteine substitution at arginine 49. We report the formation of affinity-driven disulfide bonds in the interaction of αA-R49C with ÎČB1-crystallin. To mimic cysteine thiolation in the lens, ÎČB1-crystallin was modified by a bimane probe through a disulfide linkage. Our data suggest a mechanism whereby a transient disulfide bond occurs between αA- and ÎČB1-crystallin followed by a disulfide exchange with cysteine 49 of a neighboring αA-crystallin subunit. This is the first investigation of disulfide bonds in the confine of the chaperone/substrate complex where reaction rates are favored by orders of magnitude. Covalent protein cross-links are a hallmark of age-related cataract and may be a factor in its inherited form
Collaborative edge mobile model for IoT emergency management
Traffic congestion has resulted in the loss of human lives globally as a result of failing to transfer accident victims, critical patients, medical equipment, and medications on time. With the ever-increasing volume of vehicular traffic, the convergence of Edge-based approaches has emerged as a potential platform for a Collaborative Edge Traffic Management Model. The collaborative edge model focuses on three objectives reducing the latency of the ambulance arrival to the accident, delivering the ambulance to the closest hospital and taking into consideration the patient case severity by a set of collaborating edges communicating to facilitate and manage this process
Membrane transporters studied by EPR spectroscopy: structure determination and elucidation of functional dynamics
During their mechanistic cycles membrane transporters often undergo extensive conformational changes, sampling a range of orientations, in order to complete their function. Such membrane transporters present somewhat of a challenge to conventional structural studies; indeed, crystallization of membrane-associated proteins sometimes require conditions that vary vastly from their native environments. Moreover, this technique currently only allows for visualization of single selected conformations during any one experiment. EPR spectroscopy is a magnetic resonance technique that offers a unique opportunity to study structural, environmental and dynamic properties of such proteins in their native membrane environments, as well as readily sampling their substrate-binding-induced dynamic conformational changes especially through complementary computational analyses. Here we present a review of recent studies that utilize a variety of EPR techniques in order to investigate both the structure and dynamics of a range of membrane transporters and associated proteins, focusing on both primary (ABC-type transporters) and secondary active transporters which were key interest areas of the late Professor Stephen Baldwin to whom this review is dedicated
Biochemical Characterization and Evaluation of a Brugia malayi Small Heat Shock Protein as a Vaccine against Lymphatic Filariasis
Filarial nematodes enjoy one of the longest life spans of any human pathogen due to effective immune evasion strategies developed by the parasite. Among the various immune evasion strategies exhibited by the parasite, Interleukin 10 (IL-10) productions and IL-10 mediated immune suppression has significant negative impact on the host immune system. Recently, we identified a small heat shock protein expressed by Brugia malayi (BmHsp12.6) that can bind to soluble human IL-10 receptor alpha (IL-10R) and activate IL-10 mediated effects in cell lines. In this study we show that the IL-10R binding region of BmHsp12.6 is localized to its N-terminal region. This region has significant sequence similarity to the receptor binding region of human IL-10. In vitro studies confirm that the N-terminal region of BmHsp12.6 (N-BmHsp12.6) has IL-10 like activity and the region containing the alpha crystalline domain and C-terminus of BmHsp12.6 (BmHsp12.6αc) has no IL-10 like activity. However, BmHsp12.6αc contains B cell, T cell and CTL epitopes. Members of the sHSP families are excellent vaccine candidates. Evaluation of sera samples from putatively immune endemic normal (EN) subjects showed IgG1 and IgG3 antibodies against BmHsp12.6αc and these antibodies were involved in the ADCC mediated protection. Subsequent vaccination trials with BmHsp12.6αc in a mouse model using a heterologous prime boost approach showed that 83% protection can be achieved against B. malayi L3 challenge. Results presented in this study thus show that the N-BmHsp12.6 subunit of BmHsp12.6 has immunoregulatory function, whereas, the BmHsp12.6αc subunit of BmHsp12.6 has significant vaccine potential
αA-crystallin R49Cneo mutation influences the architecture of lens fiber cell membranes and causes posterior and nuclear cataracts in mice
<p>Abstract</p> <p>Background</p> <p>αA-crystallin (CRYAA/HSPB4), a major component of all vertebrate eye lenses, is a small heat shock protein responsible for maintaining lens transparency. The R49C mutation in the αA-crystallin protein is linked with non-syndromic, hereditary human cataracts in a four-generation Caucasian family.</p> <p>Methods</p> <p>This study describes a mouse cataract model generated by insertion of a neomycin-resistant (neo<sup>r</sup>) gene into an intron of the gene encoding mutant R49C αA-crystallin. Mice carrying the neo<sup>r </sup>gene and wild-type <it>Cryaa </it>were also generated as controls. Heterozygous knock-in mice containing one wild type gene and one mutated gene for αA-crystallin (WT/R49C<sup>neo</sup>) and homozygous knock-in mice containing two mutated genes (R49C<sup>neo</sup>/R49C<sup>neo</sup>) were compared.</p> <p>Results</p> <p>By 3 weeks, WT/R49C<sup>neo </sup>mice exhibited large vacuoles in the cortical region 100 Όm from the lens surface, and by 3 months posterior and nuclear cataracts had developed. WT/R49C<sup>neo </sup>mice demonstrated severe posterior cataracts at 9 months of age, with considerable posterior nuclear migration evident in histological sections. R49C<sup>neo</sup>/R49C<sup>neo </sup>mice demonstrated nearly complete lens opacities by 5 months of age. In contrast, R49C mice in which the neo<sup>r </sup>gene was deleted by breeding with CreEIIa mice developed lens abnormalities at birth, suggesting that the neo<sup>r </sup>gene may suppress expression of mutant R49C αA-crystallin protein.</p> <p>Conclusion</p> <p>It is apparent that modification of membrane and cell-cell interactions occurs in the presence of the αA-crystallin mutation and rapidly leads to lens cell pathology <it>in vivo</it>.</p
DĂ©veloppement de rĂ©cupĂ©rateurs dâĂ©nergie sans fil Ă base de transducteurs magnĂ©toĂ©lectriques pour des applications biomĂ©dicales
E-Health and the Internet of Things (IoT) are two growing markets, related to each other by the interconnection of nomadic objects for the âquantified selfâ, where each patient can perform his own physiological tests. To that purpose, one of the technological challenges lies in the power autonomy, since energy must be supplied to the system with a minimum interaction from the outside. Hence, the development of a wireless energy harvester has a very wide range of applications. In this context, magnetoelectric (ME) materials arouse a significant scientific interest as energy transducers to transform electromagnetic energy provided from the outside into electrical energy available to power the system. ME materials are laminar composites based on piezoelectric and magnetostrictive layers, generally glued together. The device is usually connected to an electrical interface via deposited electrodes. When the ME material is driven by an external magnetic field, magnetostrictive elements are subject to mechanical constraints and motion. This motion is then transferred to the piezoelectric element which generates a voltage between its electrodes. Then, the energy must be shaped (conditioned) and managed at the system level (power management). For piezoelectric energy harvesters, many optimization strategies already exist to maximize the power flow from the transducer to the energy storage unit. This optimization takes into account the impact of the energy harvesting circuit on the overall performances of the system. Yet, to this day, no optimal solution has been identified to fit the specific constraints imposed by magnetoelectric resonators. Taking into account the specificity of magnetoelectric resonators at the system level will be a key point of this thesis. The thesis will thus aim at studying and designing the architecture of energy harvesting and conditioning systems for magnetoelectric transducers.Les technologies de la santĂ© et lâInternet des Objets (IoT) sont deux marchĂ©s en pleine croissance, liĂ©s par lâinterconnexion dâobjets nomades pour le « quantified self », oĂč chaque patient peut effectuer ses propres tests physiologiques. Ă cette fin, lâun des dĂ©fis technologiques rĂ©side dans lâautonomie de la puissance, car lâĂ©nergie doit ĂȘtre fournie au systĂšme avec un minimum dâinteraction de lâextĂ©rieur. Par consĂ©quent, le dĂ©veloppement dâun rĂ©cupĂ©rateur dâĂ©nergie sans fil a un trĂšs large Ă©ventail dâapplications. Dans ce contexte, les matĂ©riaux magnĂ©toĂ©lectriques (ME) suscitent un intĂ©rĂȘt scientifique important en tant que transducteurs dâĂ©nergie pour alimenter le systĂšme. Les matĂ©riaux ME sont des composites laminaires Ă base de couches piĂ©zoĂ©lectriques et magnĂ©tostrictives, gĂ©nĂ©ralement collĂ©es ensemble. Lorsque le matĂ©riau ME est entraĂźnĂ© par un champ magnĂ©tique externe, les Ă©lĂ©ments magnĂ©tostrictifs sont soumis Ă des contraintes mĂ©caniques et Ă des mouvements. Ce mouvement est ensuite transfĂ©rĂ© Ă lâĂ©lĂ©ment piĂ©zoĂ©lectrique qui gĂ©nĂšre une tension entre ses Ă©lectrodes. Ensuite, lâĂ©nergie doit ĂȘtre façonnĂ©e (conditionnĂ©e) et gĂ©rĂ©e au niveau du systĂšme (gestion de lâalimentation). Pour les rĂ©cupĂ©rateurs dâĂ©nergie piĂ©zoĂ©lectriques, de nombreuses stratĂ©gies dâoptimisation existent dĂ©jĂ pour maximiser le flux de puissance du transducteur Ă lâunitĂ© de stockage dâĂ©nergie. Cette optimisation prend en compte lâimpact du circuit de rĂ©cupĂ©ration dâĂ©nergie sur les performances globales du systĂšme. Pourtant, Ă ce jour, aucune solution optimale nâa Ă©tĂ© identifiĂ©e pour sâadapter aux contraintes spĂ©cifiques imposĂ©es par les rĂ©sonateurs magnĂ©toĂ©lectriques. La prise en compte de la spĂ©cificitĂ© des rĂ©sonateurs magnĂ©toĂ©lectriques au niveau du systĂšme sera un point clĂ© de cette thĂšse. La thĂšse visera donc Ă Ă©tudier et Ă concevoir lâarchitecture des systĂšmes de rĂ©cupĂ©ration et de conditionnement dâĂ©nergie pour les transducteurs magnĂ©toĂ©lectriques
DĂ©veloppement de rĂ©cupĂ©rateurs dâĂ©nergie sans fil Ă base de transducteurs magnĂ©toĂ©lectriques pour des applications biomĂ©dicales
E-Health and the Internet of Things (IoT) are two growing markets, related to each other by the interconnection of nomadic objects for the âquantified selfâ, where each patient can perform his own physiological tests. To that purpose, one of the technological challenges lies in the power autonomy, since energy must be supplied to the system with a minimum interaction from the outside. Hence, the development of a wireless energy harvester has a very wide range of applications. In this context, magnetoelectric (ME) materials arouse a significant scientific interest as energy transducers to transform electromagnetic energy provided from the outside into electrical energy available to power the system. ME materials are laminar composites based on piezoelectric and magnetostrictive layers, generally glued together. The device is usually connected to an electrical interface via deposited electrodes. When the ME material is driven by an external magnetic field, magnetostrictive elements are subject to mechanical constraints and motion. This motion is then transferred to the piezoelectric element which generates a voltage between its electrodes. Then, the energy must be shaped (conditioned) and managed at the system level (power management). For piezoelectric energy harvesters, many optimization strategies already exist to maximize the power flow from the transducer to the energy storage unit. This optimization takes into account the impact of the energy harvesting circuit on the overall performances of the system. Yet, to this day, no optimal solution has been identified to fit the specific constraints imposed by magnetoelectric resonators. Taking into account the specificity of magnetoelectric resonators at the system level will be a key point of this thesis. The thesis will thus aim at studying and designing the architecture of energy harvesting and conditioning systems for magnetoelectric transducers.Les technologies de la santĂ© et lâInternet des Objets (IoT) sont deux marchĂ©s en pleine croissance, liĂ©s par lâinterconnexion dâobjets nomades pour le « quantified self », oĂč chaque patient peut effectuer ses propres tests physiologiques. Ă cette fin, lâun des dĂ©fis technologiques rĂ©side dans lâautonomie de la puissance, car lâĂ©nergie doit ĂȘtre fournie au systĂšme avec un minimum dâinteraction de lâextĂ©rieur. Par consĂ©quent, le dĂ©veloppement dâun rĂ©cupĂ©rateur dâĂ©nergie sans fil a un trĂšs large Ă©ventail dâapplications. Dans ce contexte, les matĂ©riaux magnĂ©toĂ©lectriques (ME) suscitent un intĂ©rĂȘt scientifique important en tant que transducteurs dâĂ©nergie pour alimenter le systĂšme. Les matĂ©riaux ME sont des composites laminaires Ă base de couches piĂ©zoĂ©lectriques et magnĂ©tostrictives, gĂ©nĂ©ralement collĂ©es ensemble. Lorsque le matĂ©riau ME est entraĂźnĂ© par un champ magnĂ©tique externe, les Ă©lĂ©ments magnĂ©tostrictifs sont soumis Ă des contraintes mĂ©caniques et Ă des mouvements. Ce mouvement est ensuite transfĂ©rĂ© Ă lâĂ©lĂ©ment piĂ©zoĂ©lectrique qui gĂ©nĂšre une tension entre ses Ă©lectrodes. Ensuite, lâĂ©nergie doit ĂȘtre façonnĂ©e (conditionnĂ©e) et gĂ©rĂ©e au niveau du systĂšme (gestion de lâalimentation). Pour les rĂ©cupĂ©rateurs dâĂ©nergie piĂ©zoĂ©lectriques, de nombreuses stratĂ©gies dâoptimisation existent dĂ©jĂ pour maximiser le flux de puissance du transducteur Ă lâunitĂ© de stockage dâĂ©nergie. Cette optimisation prend en compte lâimpact du circuit de rĂ©cupĂ©ration dâĂ©nergie sur les performances globales du systĂšme. Pourtant, Ă ce jour, aucune solution optimale nâa Ă©tĂ© identifiĂ©e pour sâadapter aux contraintes spĂ©cifiques imposĂ©es par les rĂ©sonateurs magnĂ©toĂ©lectriques. La prise en compte de la spĂ©cificitĂ© des rĂ©sonateurs magnĂ©toĂ©lectriques au niveau du systĂšme sera un point clĂ© de cette thĂšse. La thĂšse visera donc Ă Ă©tudier et Ă concevoir lâarchitecture des systĂšmes de rĂ©cupĂ©ration et de conditionnement dâĂ©nergie pour les transducteurs magnĂ©toĂ©lectriques
Development of wireless energy harvesters based on magnetoelectric transducers for biomedical applications
Les technologies de la santĂ© et lâInternet des Objets (IoT) sont deux marchĂ©s en pleine croissance, liĂ©s par lâinterconnexion dâobjets nomades pour le « quantified self », oĂč chaque patient peut effectuer ses propres tests physiologiques. Ă cette fin, lâun des dĂ©fis technologiques rĂ©side dans lâautonomie de la puissance, car lâĂ©nergie doit ĂȘtre fournie au systĂšme avec un minimum dâinteraction de lâextĂ©rieur. Par consĂ©quent, le dĂ©veloppement dâun rĂ©cupĂ©rateur dâĂ©nergie sans fil a un trĂšs large Ă©ventail dâapplications. Dans ce contexte, les matĂ©riaux magnĂ©toĂ©lectriques (ME) suscitent un intĂ©rĂȘt scientifique important en tant que transducteurs dâĂ©nergie pour alimenter le systĂšme. Les matĂ©riaux ME sont des composites laminaires Ă base de couches piĂ©zoĂ©lectriques et magnĂ©tostrictives, gĂ©nĂ©ralement collĂ©es ensemble. Lorsque le matĂ©riau ME est entraĂźnĂ© par un champ magnĂ©tique externe, les Ă©lĂ©ments magnĂ©tostrictifs sont soumis Ă des contraintes mĂ©caniques et Ă des mouvements. Ce mouvement est ensuite transfĂ©rĂ© Ă lâĂ©lĂ©ment piĂ©zoĂ©lectrique qui gĂ©nĂšre une tension entre ses Ă©lectrodes. Ensuite, lâĂ©nergie doit ĂȘtre façonnĂ©e (conditionnĂ©e) et gĂ©rĂ©e au niveau du systĂšme (gestion de lâalimentation). Pour les rĂ©cupĂ©rateurs dâĂ©nergie piĂ©zoĂ©lectriques, de nombreuses stratĂ©gies dâoptimisation existent dĂ©jĂ pour maximiser le flux de puissance du transducteur Ă lâunitĂ© de stockage dâĂ©nergie. Cette optimisation prend en compte lâimpact du circuit de rĂ©cupĂ©ration dâĂ©nergie sur les performances globales du systĂšme. Pourtant, Ă ce jour, aucune solution optimale nâa Ă©tĂ© identifiĂ©e pour sâadapter aux contraintes spĂ©cifiques imposĂ©es par les rĂ©sonateurs magnĂ©toĂ©lectriques. La prise en compte de la spĂ©cificitĂ© des rĂ©sonateurs magnĂ©toĂ©lectriques au niveau du systĂšme sera un point clĂ© de cette thĂšse. La thĂšse visera donc Ă Ă©tudier et Ă concevoir lâarchitecture des systĂšmes de rĂ©cupĂ©ration et de conditionnement dâĂ©nergie pour les transducteurs magnĂ©toĂ©lectriques.E-Health and the Internet of Things (IoT) are two growing markets, related to each other by the interconnection of nomadic objects for the âquantified selfâ, where each patient can perform his own physiological tests. To that purpose, one of the technological challenges lies in the power autonomy, since energy must be supplied to the system with a minimum interaction from the outside. Hence, the development of a wireless energy harvester has a very wide range of applications. In this context, magnetoelectric (ME) materials arouse a significant scientific interest as energy transducers to transform electromagnetic energy provided from the outside into electrical energy available to power the system. ME materials are laminar composites based on piezoelectric and magnetostrictive layers, generally glued together. The device is usually connected to an electrical interface via deposited electrodes. When the ME material is driven by an external magnetic field, magnetostrictive elements are subject to mechanical constraints and motion. This motion is then transferred to the piezoelectric element which generates a voltage between its electrodes. Then, the energy must be shaped (conditioned) and managed at the system level (power management). For piezoelectric energy harvesters, many optimization strategies already exist to maximize the power flow from the transducer to the energy storage unit. This optimization takes into account the impact of the energy harvesting circuit on the overall performances of the system. Yet, to this day, no optimal solution has been identified to fit the specific constraints imposed by magnetoelectric resonators. Taking into account the specificity of magnetoelectric resonators at the system level will be a key point of this thesis. The thesis will thus aim at studying and designing the architecture of energy harvesting and conditioning systems for magnetoelectric transducers
Power-limiting phenomena in a magnetoelectric transducer for wireless power transfer
International audienc
- âŠ