The solid-state photo-CIDNP effect is the occurrence of a non-Boltzmann nuclear spin polarization... more The solid-state photo-CIDNP effect is the occurrence of a non-Boltzmann nuclear spin polarization in rigid samples upon illumination. For solid-state NMR, which can detect this enhanced nuclear polarization as a strong modification of signal intensity, the effect allows for new classes of experiments. Currently, the photo- and spin-chemical machinery of various RCs is studied by photo-CIDNP MAS NMR in detail. Until now, the effect has only been observed at high magnetic fields with 13C and 15N MAS NMR and in natural photosynthetic RC preparations in which blocking of the acceptor leads to cyclic electron transfer. In terms of irreversible thermodynamics, the high-order spin structure of the initial radical pair can be considered as a transient order phenomenon emerging under non-equilibrium conditions and as a first manifestation of order in the photosynthetic process. The solid-state photo-CIDNP effect appears to be an intrinsic property of natural RCs. The conditions of its occurrence seem to be conserved in evolution. The effect may be based on the same fundamental principles as the highly optimized electron transfer. Hence, the effect may allow for guiding artificial photosynthesis.
In the last two decades, Magic Angle Spinning (MAS) NMR has created its own niche in studies invo... more In the last two decades, Magic Angle Spinning (MAS) NMR has created its own niche in studies involving photosynthetic membrane protein complexes, owing to its ability to provide structural and functional information at atomic resolution of membrane proteins when in the membrane, in the natural environment. The light-harvesting two (LH2) transmembrane complex from Rhodopseudomonas acidophila is used to illustrate the procedure of the technique applicable in photosynthesis research. One-and two-dimensional solid-state NMR experiments involving 13 C-and 15 N-labeled LH2 complexes allow to make a sequence-specific assignment of NMR signals, which forms the basis for resolving structural details and the assessment of charge transfer, electronic delocalization effects, and functional strain in the ground state.
Cyanobacteria are widely used as model organism of oxygenic photosynthesis due to being the simpl... more Cyanobacteria are widely used as model organism of oxygenic photosynthesis due to being the simplest photosynthetic organisms containing both photosystem I and II (PSI and PSII). Photochemically induced dynamic nuclear polarization (photo-CIDNP) 13C magic-angle spinning (MAS) NMR is a powerful tool in understanding the photosynthesis machinery down to atomic level. Combined with selective isotope enrichment this technique has now opened the door to study primary charge separation in whole living cells. Here, we present the first photo-CIDNP observed in whole cells of the cyanobacterium Synechocystis.
The presence of amyloid plaques in the brain is one of prominent histological features of Alzheim... more The presence of amyloid plaques in the brain is one of prominent histological features of Alzheimer's disease. However, imaging of amyloid plaques in vivo in humans is not yet feasible. Recent technical advances in high resolution magnetic resonance imaging (MRI) methods in mice have enabled not only the detection of amyloid plaques in vivo but also allowed to monitor the development of these plaques with age in the same animals. Further technical improvements to visualize small plaques at early stages at ultrahigh magnetic fields are underway. This review summarizes some of the current developments in visualizing AD plaques in vivo in mice and highlights their future impact on drug discovery. Furthermore potential application and challenges of translation of these methods for visualizing plaques in human are discussed.
The existing literature on the magnetic resonance imaging of murine models of Alzheimer's disease... more The existing literature on the magnetic resonance imaging of murine models of Alzheimer's disease is reviewed. Particular attention is paid to the possibilities for the early detection of the disease. To this effect, not only are relaxometric and volumetric approaches discussed, but also mathematical models for plaque distribution and aggregation. Image analysis plays a prominent role in this line of research, as stochastic image models and texture analysis have shown some success in the classification of subjects affected by Alzheimer's disease. It is concluded that relaxometric approaches seem to be a promising candidate for the task at hand, especially when combined with sophisticated image analysis, and when data from more than one time-point is available. There have been few longitudinal studies of mice models so far, so this direction of research warrants future efforts.
Zebrafish cancer models are fast gaining ground in cancer research. Most tumors in zebrafish deve... more Zebrafish cancer models are fast gaining ground in cancer research. Most tumors in zebrafish develop late in life, when fish are no longer transparent, limiting in vivo optical imaging methods. Thus, noninvasive imaging to track tumor in adult zebrafish remains challenging. In this study, we applied magnetic resonance microimaging (microMRI) to track spontaneous melanomas in stable transgenic zebrafish models expressing an RAS oncoprotein and lacking P53 (mitf:Ras::mitf:GFP X p53(-/-)). Tumors in live adult zebrafish were observed at various locations using a T(2)-weighted fast spin echo sequence at 9.4 T. Further, live imaging of tumors at ultrahigh field (17.6 T) revealed significant tumor heterogeneity. This heterogeneity was also confirmed by the significant differences in transverse relaxation time, T(2) measured in various regions of tumor. To our knowledge, this is the first report demonstrating the application of microMRI to detect the locations, invasion status, and characteristics of internal melanomas in zebrafish and suggesting that noninvasive microMRI can be applied for longitudinal studies to track tumor development and real-time assessment of therapeutic effects in zebrafish tumor models.
In nanosecond-laser flash photo-CIDNP MAS NMR, polarization generation (PG) proceeds much faster ... more In nanosecond-laser flash photo-CIDNP MAS NMR, polarization generation (PG) proceeds much faster than longitudinal spin relaxation. With a nanosecond-laser setup linked to the NMR console the repetition time of the experiment is then limited by the minimum recycle delay of the NMR spectrometer and the maximum repetition rate of laser flashes. These limits can only be reached if polarization left after the NMR experiment is completely canceled before the next laser flash. We introduce a presaturation pulse sequence, based on three (pi/2) (13)C pulses and optimized timing and phase cycling that allows for such efficient polarization extinction (PE). The technique is demonstrated on selectively isotope labeled bacterial reaction centers (RCs) of Rhodobacter (Rb.) sphaeroides wildtype (WT). High-quality (13)C photo-CIDNP MAS NMR spectra are obtained using cycle rates up to 4 Hz. The PE-PG strategy proposed here provides a general experimental scheme for reduction of measurement time in magnetic resonance experiments based on fast PG.
Magnetic resonance microscopy (MRM) is an imaging modality that allows for noninvasive acquisitio... more Magnetic resonance microscopy (MRM) is an imaging modality that allows for noninvasive acquisition of high-resolution images in intact opaque animals. The zebrafish (Danio rerio) is an important model organism for the study of vertebrate biology. However, optical in vivo studies in zebrafish are restricted to very early developmental stages due to the opacity of the juvenile and adult stages. Application of high resolution MRM has not yet been explored in adult zebrafish. In this study we applied and optimized high resolution MRM methods to examine anatomical structures noninvasively in adult zebrafish. Clear morphological proton images were obtained by T(2)-weighted spin echo and rapid acquisition with rapid acquisition with relaxation enhancement (RARE) sequences which revealed many anatomical details in the entire intact zebrafish at a magnetic field strength of 9.4 T. In addition, in vivo imaging of adult zebrafish revealed sufficient anatomical details. To our knowledge this is the first report of the application of high resolution MRM to study detailed anatomical structures in adult zebrafish.
Objectives To investigate, using a Dutch model, whether and under what variables framed for other... more Objectives To investigate, using a Dutch model, whether and under what variables framed for other European countries screening for human papillomavirus (HPV) is preferred over cytology screening for cervical cancer, and to calculate the preferred number of examinations over a woman's lifetime. Design Cost effectiveness analysis based on a Dutch simulation model. Base case analyses investigated the cost effectiveness of more than 1500 different screening policies using the microsimulation model. Subsequently, the policies were compared for five different scenarios that represent different possible scenarios (risk of cervical cancer, previous screening, quality associated test characteristics, costs of testing, and prevalence of HPV). Setting Various European countries.
The solid-state photo-CIDNP effect is the occurrence of a non-Boltzmann nuclear spin polarization... more The solid-state photo-CIDNP effect is the occurrence of a non-Boltzmann nuclear spin polarization in rigid samples upon illumination. For solid-state NMR, which can detect this enhanced nuclear polarization as a strong modification of signal intensity, the effect allows for new classes of experiments. Currently, the photo- and spin-chemical machinery of various RCs is studied by photo-CIDNP MAS NMR in detail. Until now, the effect has only been observed at high magnetic fields with 13C and 15N MAS NMR and in natural photosynthetic RC preparations in which blocking of the acceptor leads to cyclic electron transfer. In terms of irreversible thermodynamics, the high-order spin structure of the initial radical pair can be considered as a transient order phenomenon emerging under non-equilibrium conditions and as a first manifestation of order in the photosynthetic process. The solid-state photo-CIDNP effect appears to be an intrinsic property of natural RCs. The conditions of its occurrence seem to be conserved in evolution. The effect may be based on the same fundamental principles as the highly optimized electron transfer. Hence, the effect may allow for guiding artificial photosynthesis.
In the last two decades, Magic Angle Spinning (MAS) NMR has created its own niche in studies invo... more In the last two decades, Magic Angle Spinning (MAS) NMR has created its own niche in studies involving photosynthetic membrane protein complexes, owing to its ability to provide structural and functional information at atomic resolution of membrane proteins when in the membrane, in the natural environment. The light-harvesting two (LH2) transmembrane complex from Rhodopseudomonas acidophila is used to illustrate the procedure of the technique applicable in photosynthesis research. One-and two-dimensional solid-state NMR experiments involving 13 C-and 15 N-labeled LH2 complexes allow to make a sequence-specific assignment of NMR signals, which forms the basis for resolving structural details and the assessment of charge transfer, electronic delocalization effects, and functional strain in the ground state.
Cyanobacteria are widely used as model organism of oxygenic photosynthesis due to being the simpl... more Cyanobacteria are widely used as model organism of oxygenic photosynthesis due to being the simplest photosynthetic organisms containing both photosystem I and II (PSI and PSII). Photochemically induced dynamic nuclear polarization (photo-CIDNP) 13C magic-angle spinning (MAS) NMR is a powerful tool in understanding the photosynthesis machinery down to atomic level. Combined with selective isotope enrichment this technique has now opened the door to study primary charge separation in whole living cells. Here, we present the first photo-CIDNP observed in whole cells of the cyanobacterium Synechocystis.
The presence of amyloid plaques in the brain is one of prominent histological features of Alzheim... more The presence of amyloid plaques in the brain is one of prominent histological features of Alzheimer's disease. However, imaging of amyloid plaques in vivo in humans is not yet feasible. Recent technical advances in high resolution magnetic resonance imaging (MRI) methods in mice have enabled not only the detection of amyloid plaques in vivo but also allowed to monitor the development of these plaques with age in the same animals. Further technical improvements to visualize small plaques at early stages at ultrahigh magnetic fields are underway. This review summarizes some of the current developments in visualizing AD plaques in vivo in mice and highlights their future impact on drug discovery. Furthermore potential application and challenges of translation of these methods for visualizing plaques in human are discussed.
The existing literature on the magnetic resonance imaging of murine models of Alzheimer's disease... more The existing literature on the magnetic resonance imaging of murine models of Alzheimer's disease is reviewed. Particular attention is paid to the possibilities for the early detection of the disease. To this effect, not only are relaxometric and volumetric approaches discussed, but also mathematical models for plaque distribution and aggregation. Image analysis plays a prominent role in this line of research, as stochastic image models and texture analysis have shown some success in the classification of subjects affected by Alzheimer's disease. It is concluded that relaxometric approaches seem to be a promising candidate for the task at hand, especially when combined with sophisticated image analysis, and when data from more than one time-point is available. There have been few longitudinal studies of mice models so far, so this direction of research warrants future efforts.
Zebrafish cancer models are fast gaining ground in cancer research. Most tumors in zebrafish deve... more Zebrafish cancer models are fast gaining ground in cancer research. Most tumors in zebrafish develop late in life, when fish are no longer transparent, limiting in vivo optical imaging methods. Thus, noninvasive imaging to track tumor in adult zebrafish remains challenging. In this study, we applied magnetic resonance microimaging (microMRI) to track spontaneous melanomas in stable transgenic zebrafish models expressing an RAS oncoprotein and lacking P53 (mitf:Ras::mitf:GFP X p53(-/-)). Tumors in live adult zebrafish were observed at various locations using a T(2)-weighted fast spin echo sequence at 9.4 T. Further, live imaging of tumors at ultrahigh field (17.6 T) revealed significant tumor heterogeneity. This heterogeneity was also confirmed by the significant differences in transverse relaxation time, T(2) measured in various regions of tumor. To our knowledge, this is the first report demonstrating the application of microMRI to detect the locations, invasion status, and characteristics of internal melanomas in zebrafish and suggesting that noninvasive microMRI can be applied for longitudinal studies to track tumor development and real-time assessment of therapeutic effects in zebrafish tumor models.
In nanosecond-laser flash photo-CIDNP MAS NMR, polarization generation (PG) proceeds much faster ... more In nanosecond-laser flash photo-CIDNP MAS NMR, polarization generation (PG) proceeds much faster than longitudinal spin relaxation. With a nanosecond-laser setup linked to the NMR console the repetition time of the experiment is then limited by the minimum recycle delay of the NMR spectrometer and the maximum repetition rate of laser flashes. These limits can only be reached if polarization left after the NMR experiment is completely canceled before the next laser flash. We introduce a presaturation pulse sequence, based on three (pi/2) (13)C pulses and optimized timing and phase cycling that allows for such efficient polarization extinction (PE). The technique is demonstrated on selectively isotope labeled bacterial reaction centers (RCs) of Rhodobacter (Rb.) sphaeroides wildtype (WT). High-quality (13)C photo-CIDNP MAS NMR spectra are obtained using cycle rates up to 4 Hz. The PE-PG strategy proposed here provides a general experimental scheme for reduction of measurement time in magnetic resonance experiments based on fast PG.
Magnetic resonance microscopy (MRM) is an imaging modality that allows for noninvasive acquisitio... more Magnetic resonance microscopy (MRM) is an imaging modality that allows for noninvasive acquisition of high-resolution images in intact opaque animals. The zebrafish (Danio rerio) is an important model organism for the study of vertebrate biology. However, optical in vivo studies in zebrafish are restricted to very early developmental stages due to the opacity of the juvenile and adult stages. Application of high resolution MRM has not yet been explored in adult zebrafish. In this study we applied and optimized high resolution MRM methods to examine anatomical structures noninvasively in adult zebrafish. Clear morphological proton images were obtained by T(2)-weighted spin echo and rapid acquisition with rapid acquisition with relaxation enhancement (RARE) sequences which revealed many anatomical details in the entire intact zebrafish at a magnetic field strength of 9.4 T. In addition, in vivo imaging of adult zebrafish revealed sufficient anatomical details. To our knowledge this is the first report of the application of high resolution MRM to study detailed anatomical structures in adult zebrafish.
Objectives To investigate, using a Dutch model, whether and under what variables framed for other... more Objectives To investigate, using a Dutch model, whether and under what variables framed for other European countries screening for human papillomavirus (HPV) is preferred over cytology screening for cervical cancer, and to calculate the preferred number of examinations over a woman's lifetime. Design Cost effectiveness analysis based on a Dutch simulation model. Base case analyses investigated the cost effectiveness of more than 1500 different screening policies using the microsimulation model. Subsequently, the policies were compared for five different scenarios that represent different possible scenarios (risk of cervical cancer, previous screening, quality associated test characteristics, costs of testing, and prevalence of HPV). Setting Various European countries.
Uploads
Papers by alia alia