Jüri Jarvet - Academia.edu (original) (raw)

Papers by Jüri Jarvet

Research Square (Research Square), Dec 5, 2023

Communications chemistry, Aug 3, 2023

Journal of Magnetic Resonance, 1997

Biochemistry, May 17, 2012

Biochemistry, May 10, 2023

Biophysical Journal, Feb 1, 2018

Acta Neuropathologica, Jul 17, 2014

Biophysical Journal, Feb 1, 2017

Biochemistry, Dec 3, 2015

Self-assembly of amyloid β (Aβ) peptide molecules into large aggregates is a naturally occurring ... more Self-assembly of amyloid β (Aβ) peptide molecules into large aggregates is a naturally occurring process driven in aqueous solution by a dynamic interplay between hydrophobic interactions among Aβ molecules, which promote aggregation, and steric and overall electrostatic hindrance, which stifles it. Aβ self-association is entropically unfavorable, as it implies order increase in the system, but under favorable kinetic conditions, the process proceeds at appreciable rates, yielding Aβ aggregates of different sizes and structures. Despite the great relevance and extensive research efforts, detailed kinetic mechanisms underlying Aβ aggregation remain only partially understood. In this study, fluorescence correlation spectroscopy (FCS) and Thioflavin T (ThT) were used to monitor the time dependent growth of structured aggregates and characterize multiple components during the aggregation of Aβ peptides in a heterogeneous aqueous solution. To this aim, we collected data during a relatively large number of observation periods, 30 consecutive measurements lasting 10 s each, at what we consider to be a constant time point in the slow aggregation process. This approach enabled monitoring the formation of nanomolar concentrations of structured amyloid aggregates and demonstrated the changing distribution of amyloid aggregate sizes throughout the aggregation process. We identified aggregates of different sizes with molecular weight from 260 to more than 1 × 10(6) kDa and revealed the hitherto unobserved kinetic turnover of intermediates during Aβ aggregation. The effect of different Aβ concentrations, Aβ:ThT ratios, differences between the 40 (Aβ40) and 42 (Aβ42) residue long variants of Aβ, and the effect of stirring were also examined.

Journal of Magnetic Resonance, Feb 1, 2001

Chemical Society Reviews, 2019

One of the grand challenges of biophysical chemistry is to understand the principles that govern ... more One of the grand challenges of biophysical chemistry is to understand the principles that govern protein aggregation leading to amyloid fibrils, which is a highly complex and sensitive process. This review provides a comprehensive overview of how amyloid aggregation is affected by the variousin vivoconstituents and conditions.

Magnetic Resonance in Chemistry, Nov 8, 2002

ABSTRACT PFG-NMR methods were used to measure the translational diffusion coefficients for the Aβ... more ABSTRACT PFG-NMR methods were used to measure the translational diffusion coefficients for the Aβ peptide involved in Alzheimer's disease and also for a series of fragments of this peptide. The peptides ranged from a pentamer to the full length Aβ(1–40). They were studied at 25° C and physiological pH in aqueous solution. The measured diffusion coefficients, including those of known monomeric peptides, were fitted without systematic deviations to a scaling law function of the molecular mass. We concluded that under these conditions Aβ(1–40) is in monomeric form. From the diffusion coefficient data, hydrodynamic radii rH were evaluated for the peptides. When combining our results on non- or weakly structured peptides with previously reported results on denatured proteins, we found that the hydrodynamic radii for the combined dataset could be well described by the same scaling law relating them to the molecular weight. The same law would even encompass data on single amino acids and di- and tripeptides measured by classical methods. From the above-mentioned experimental data, scaling law parameters were determined. The relation between the measured hydrodynamic radius (rH) and the molecular weight of the polypeptide chain (Mr) for amino acids, peptides and denatured proteins is rH = 0.27Mr0.50 Å. There is a remarkably good fit to this function for the measured hydrodynamic radii in a large range, almost three orders of magnitude, of molecular weights. The numerical value of the exponent, 0.5, is an indication that these polymers behave as Gaussian chains. Copyright © 2002 John Wiley & Sons, Ltd.

Journal of Biomolecular NMR, Jul 27, 2007

Biochemistry, Dec 7, 2005

Cancer Letters, Oct 1, 2005

Non-invasive biological information about residual neuroblastoma tumour tissue could allow treatm... more Non-invasive biological information about residual neuroblastoma tumour tissue could allow treatment monitoring without the need for repeated biopsies. Magnetic resonance spectroscopy (MRS) can be performed with standard MR-scanners, providing specific biochemical information from selected tumour regions. By proton 1H-MRS, lipids, certain amino acids and lactate can be detected and their relative concentrations estimated in vivo. Using experimental models of neuroblastoma, we have described the potential of 1H-MRS for the prediction of tumour tissue viability and treatment response. Whereas viable neuroblastoma tissue is dominated by the choline 1H-MRS resonance, cell death as a consequence of spontaneous necrosis or successful treatment with chemotherapy, angiogenesis inhibitors, or NSAIDs is associated with decreased choline content. Therapy-induced neuroblastoma cell death is also associated with enhanced 1H-MRS resonances from mobile lipids and polyunsaturated fatty acids. The mobile lipid/choline ratio correlates significantly with cell death and based on the dynamics of this ratio tumour regression or continued growth (drug resistance) after chemotherapy can be predicted in vivo. The implications of these findings are discussed with focus on the potentials and limitations of introducing 1H-MRS for clinical assessment of treatment response in children with neuroblastoma. Biochemical monitoring of neuroblastoma with 1H-MRS could enable tailoring of individual therapy as well as provide early pharmacodynamic evaluation of novel therapeutic modalities.

Journal of Molecular Biology, May 1, 2004

A new early-onset form of Alzheimer's disease (AD) was described recently where a point ... more A new early-onset form of Alzheimer's disease (AD) was described recently where a point mutation was discovered in codon 693 of the β-amyloid (Aβ) precursor protein gene, the Arctic mutation. The mutation translates into a single amino acid substitution, glutamic acid→glycine, in position 22 of the Aβ peptide. The mutation carriers have lower plasma levels of Aβ than normal, while in vitro studies show that Aβ1–40E22G protofibril formation is significantly enhanced. We have explored the nature of the Aβ1–40E22G peptide in more detail, in particular the protofibrils. Using size-exclusion chromatography (SEC) and circular dichroism spectroscopy (CD) kinetic and secondary structural characteristics were compared with other Aβ1–40 peptides and the Aβ12–28 fragment, all having single amino acid substitutions in position 22. We have found that Aβ1–40E22G protofibrils are a group of comparatively stabile β-sheet-containing oligomers with a heterogeneous size distribution, ranging from >100 kDa to >3000 kDa. Small Aβ1–40E22G protofibrils are generated about 400 times faster than large ones. Salt promotes their formation, which significantly exceeds all the other peptides studied here, including the Dutch mutation Aβ1–40E22Q. Position 22 substitutions had significant effects on aggregation kinetics of Aβ1–40 and in Aβ12–28, although the qualitative aspects of the effects differed between the native peptide and the fragment, as no protofibrils were formed by the fragments. The rank order of protofibril formation of Aβ1–40 and its variants was the same as the rank order of the length of the nucleation/lag phase of the Aβ12–28 fragments, E22V>E22A≫E22G>E22Q≫E22, and correlated with the degree of hydrophobicity of the position 22 substituent. The molecular mass of peptide monomers and protofibrils were estimated better in SEC studies using linear rather than globular calibration standards. The characteristics of the Aβ1–40E22G suggest an important role for the peptide in the neuropathogenesis in the Arctic form of AD.

Magnetic Resonance in Chemistry, 2006

Journal of Magnetic Resonance, Series B, Apr 1, 1996

Research Square (Research Square), Dec 5, 2023

Communications chemistry, Aug 3, 2023

Journal of Magnetic Resonance, 1997

Biochemistry, May 17, 2012

Biochemistry, May 10, 2023

Biophysical Journal, Feb 1, 2018

Acta Neuropathologica, Jul 17, 2014

Biophysical Journal, Feb 1, 2017

Biochemistry, Dec 3, 2015

Self-assembly of amyloid β (Aβ) peptide molecules into large aggregates is a naturally occurring ... more Self-assembly of amyloid β (Aβ) peptide molecules into large aggregates is a naturally occurring process driven in aqueous solution by a dynamic interplay between hydrophobic interactions among Aβ molecules, which promote aggregation, and steric and overall electrostatic hindrance, which stifles it. Aβ self-association is entropically unfavorable, as it implies order increase in the system, but under favorable kinetic conditions, the process proceeds at appreciable rates, yielding Aβ aggregates of different sizes and structures. Despite the great relevance and extensive research efforts, detailed kinetic mechanisms underlying Aβ aggregation remain only partially understood. In this study, fluorescence correlation spectroscopy (FCS) and Thioflavin T (ThT) were used to monitor the time dependent growth of structured aggregates and characterize multiple components during the aggregation of Aβ peptides in a heterogeneous aqueous solution. To this aim, we collected data during a relatively large number of observation periods, 30 consecutive measurements lasting 10 s each, at what we consider to be a constant time point in the slow aggregation process. This approach enabled monitoring the formation of nanomolar concentrations of structured amyloid aggregates and demonstrated the changing distribution of amyloid aggregate sizes throughout the aggregation process. We identified aggregates of different sizes with molecular weight from 260 to more than 1 × 10(6) kDa and revealed the hitherto unobserved kinetic turnover of intermediates during Aβ aggregation. The effect of different Aβ concentrations, Aβ:ThT ratios, differences between the 40 (Aβ40) and 42 (Aβ42) residue long variants of Aβ, and the effect of stirring were also examined.

Journal of Magnetic Resonance, Feb 1, 2001

Chemical Society Reviews, 2019

One of the grand challenges of biophysical chemistry is to understand the principles that govern ... more One of the grand challenges of biophysical chemistry is to understand the principles that govern protein aggregation leading to amyloid fibrils, which is a highly complex and sensitive process. This review provides a comprehensive overview of how amyloid aggregation is affected by the variousin vivoconstituents and conditions.

Magnetic Resonance in Chemistry, Nov 8, 2002

ABSTRACT PFG-NMR methods were used to measure the translational diffusion coefficients for the Aβ... more ABSTRACT PFG-NMR methods were used to measure the translational diffusion coefficients for the Aβ peptide involved in Alzheimer's disease and also for a series of fragments of this peptide. The peptides ranged from a pentamer to the full length Aβ(1–40). They were studied at 25° C and physiological pH in aqueous solution. The measured diffusion coefficients, including those of known monomeric peptides, were fitted without systematic deviations to a scaling law function of the molecular mass. We concluded that under these conditions Aβ(1–40) is in monomeric form. From the diffusion coefficient data, hydrodynamic radii rH were evaluated for the peptides. When combining our results on non- or weakly structured peptides with previously reported results on denatured proteins, we found that the hydrodynamic radii for the combined dataset could be well described by the same scaling law relating them to the molecular weight. The same law would even encompass data on single amino acids and di- and tripeptides measured by classical methods. From the above-mentioned experimental data, scaling law parameters were determined. The relation between the measured hydrodynamic radius (rH) and the molecular weight of the polypeptide chain (Mr) for amino acids, peptides and denatured proteins is rH = 0.27Mr0.50 Å. There is a remarkably good fit to this function for the measured hydrodynamic radii in a large range, almost three orders of magnitude, of molecular weights. The numerical value of the exponent, 0.5, is an indication that these polymers behave as Gaussian chains. Copyright © 2002 John Wiley & Sons, Ltd.

Journal of Biomolecular NMR, Jul 27, 2007

Biochemistry, Dec 7, 2005

Cancer Letters, Oct 1, 2005

Non-invasive biological information about residual neuroblastoma tumour tissue could allow treatm... more Non-invasive biological information about residual neuroblastoma tumour tissue could allow treatment monitoring without the need for repeated biopsies. Magnetic resonance spectroscopy (MRS) can be performed with standard MR-scanners, providing specific biochemical information from selected tumour regions. By proton 1H-MRS, lipids, certain amino acids and lactate can be detected and their relative concentrations estimated in vivo. Using experimental models of neuroblastoma, we have described the potential of 1H-MRS for the prediction of tumour tissue viability and treatment response. Whereas viable neuroblastoma tissue is dominated by the choline 1H-MRS resonance, cell death as a consequence of spontaneous necrosis or successful treatment with chemotherapy, angiogenesis inhibitors, or NSAIDs is associated with decreased choline content. Therapy-induced neuroblastoma cell death is also associated with enhanced 1H-MRS resonances from mobile lipids and polyunsaturated fatty acids. The mobile lipid/choline ratio correlates significantly with cell death and based on the dynamics of this ratio tumour regression or continued growth (drug resistance) after chemotherapy can be predicted in vivo. The implications of these findings are discussed with focus on the potentials and limitations of introducing 1H-MRS for clinical assessment of treatment response in children with neuroblastoma. Biochemical monitoring of neuroblastoma with 1H-MRS could enable tailoring of individual therapy as well as provide early pharmacodynamic evaluation of novel therapeutic modalities.

Journal of Molecular Biology, May 1, 2004

A new early-onset form of Alzheimer's disease (AD) was described recently where a point ... more A new early-onset form of Alzheimer's disease (AD) was described recently where a point mutation was discovered in codon 693 of the β-amyloid (Aβ) precursor protein gene, the Arctic mutation. The mutation translates into a single amino acid substitution, glutamic acid→glycine, in position 22 of the Aβ peptide. The mutation carriers have lower plasma levels of Aβ than normal, while in vitro studies show that Aβ1–40E22G protofibril formation is significantly enhanced. We have explored the nature of the Aβ1–40E22G peptide in more detail, in particular the protofibrils. Using size-exclusion chromatography (SEC) and circular dichroism spectroscopy (CD) kinetic and secondary structural characteristics were compared with other Aβ1–40 peptides and the Aβ12–28 fragment, all having single amino acid substitutions in position 22. We have found that Aβ1–40E22G protofibrils are a group of comparatively stabile β-sheet-containing oligomers with a heterogeneous size distribution, ranging from >100 kDa to >3000 kDa. Small Aβ1–40E22G protofibrils are generated about 400 times faster than large ones. Salt promotes their formation, which significantly exceeds all the other peptides studied here, including the Dutch mutation Aβ1–40E22Q. Position 22 substitutions had significant effects on aggregation kinetics of Aβ1–40 and in Aβ12–28, although the qualitative aspects of the effects differed between the native peptide and the fragment, as no protofibrils were formed by the fragments. The rank order of protofibril formation of Aβ1–40 and its variants was the same as the rank order of the length of the nucleation/lag phase of the Aβ12–28 fragments, E22V>E22A≫E22G>E22Q≫E22, and correlated with the degree of hydrophobicity of the position 22 substituent. The molecular mass of peptide monomers and protofibrils were estimated better in SEC studies using linear rather than globular calibration standards. The characteristics of the Aβ1–40E22G suggest an important role for the peptide in the neuropathogenesis in the Arctic form of AD.

Magnetic Resonance in Chemistry, 2006

Journal of Magnetic Resonance, Series B, Apr 1, 1996