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- Gruschke, Steffi, et al.
(författare)
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Proteins at the Polypeptide Tunnel Exit of the Yeast Mitochondrial Ribosome
- 2010
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 285:25, s. 19022-19028
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Tidskriftsartikel (refereegranskat)abstract
- Oxidative phosphorylation in mitochondria requires the synthesis of proteins encoded in the mitochondrial DNA. The mitochondrial translation machinery differs significantly from that of the bacterial ancestor of the organelle. This is especially evident from many mitochondria-specific ribosomal proteins. An important site of the ribosome is the polypeptide tunnel exit. Here, nascent chains are exposed to an aqueous environment for the first time. Many biogenesis factors interact with the tunnel exit of pro- and eukaryotic ribosomes to help the newly synthesized proteins to mature. To date, nothing is known about the organization of the tunnel exit of mitochondrial ribosomes. We therefore undertook a comprehensive approach to determine the composition of the yeast mitochondrial ribosomal tunnel exit. Mitochondria contain homologues of the ribosomal proteins located at this site in bacterial ribosomes. Here, we identified proteins located in their proximity by chemical cross-linking and mass spectrometry. Our analysis revealed a complex network of interacting proteins including proteins and protein domains specific to mitochondrial ribosomes. This network includes Mba1, the membrane-bound ribosome receptor of the inner membrane, as well as Mrpl3, Mrpl13, and Mrpl27, which constitute ribosomal proteins exclusively found in mitochondria. This unique architecture of the tunnel exit is presumably an adaptation of the translation system to the specific requirements of the organelle.
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| 3. |
- Perlaki, Gabor, et al.
(författare)
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Volumetric gray matter measures of amygdala and accumbens in childhood overweight/obesity
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Neuroimaging data suggest that pediatric overweight and obesity are associated with morphological alterations in gray matter (GM) brain structures, but previous studies using mainly voxel-based morphometry (VBM) showed inconsistent results. Here, we aimed to examine the relationship between youth obesity and the volume of predefined reward system structures using magnetic resonance (MR) volumetry. We also aimed to complement volumetry with VBM-style analysis. Methods Fifty-one Caucasian young subjects (32 females; mean age: 13.8±1.9, range: 10.2–16.5 years) were included. Subjects were selected from a subsample of the I.Family study examined in the Hungarian center. A T1-weighted 1 mm3 isotropic resolution image was acquired. Age- and sex-standardized body mass index (zBMI) was assessed at the day of MRI and ~1.89 years (mean±SD: 689±188 days) before the examination. Obesity related GM alterations were investigated using MR volumetry in five predefined brain structures presumed to play crucial roles in body weight regulation (hippocampus, amygdala, accumbens, caudate, putamen), as well as whole-brain and regional VBM. Results The volumes of accumbens and amygdala showed significant positive correlations with zBMI, while their GM densities were inversely related to zBMI. Voxel-based GM mass also showed significant negative correlation with zBMI when investigated in the predefined amygdala region, but this relationship was mediated by GM density. Conclusions Overweight/obesity related morphometric brain differences already seem to be present in children/adolescents. Our work highlights the disparity between volume and VBM-derived measures and that GM mass (combination of volume and density) is not informative in the context of obesity related volumetric changes. To better characterize the association between childhood obesity and GM morphometry, a combination of volumetric segmentation and VBM methods, as well as future longitudinal studies are necessary. Our results suggest that childhood obesity is associated with enlarged structural volumes, but decreased GM density in the reward system. © 2018 Perlaki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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- Shalgunov, Vladimir, et al.
(författare)
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Pretargeted imaging beyond the blood-brain barrier
- 2023
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Ingår i: RSC Medicinal Chemistry. - : Royal Society of Chemistry. - 2632-8682. ; 14:3, s. 444-453
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Tidskriftsartikel (refereegranskat)abstract
- Pretargeting is a powerful nuclear imaging strategy to achieve enhanced imaging contrast for nanomedicines and reduce the radiation burden to healthy tissue. Pretargeting is based on bioorthogonal chemistry. The most attractive reaction for this purpose is currently the tetrazine ligation, which occurs between trans-cyclooctene (TCO) tags and tetrazines (Tzs). Pretargeted imaging beyond the blood-brain barrier (BBB) is challenging and has not been reported thus far. In this study, we developed Tz imaging agents that are capable of ligating in vivo to targets beyond the BBB. We chose to develop F-18-labeled Tzs as they can be applied to positron emission tomography (PET) - the most powerful molecular imaging technology. Fluorine-18 is an ideal radionuclide for PET due to its almost ideal decay properties. As a non-metal radionuclide, fluorine-18 also allows for development of Tzs with physicochemical properties enabling passive brain diffusion. To develop these imaging agents, we applied a rational drug design approach. This approach was based on estimated and experimentally determined parameters such as the BBB score, pretargeted autoradiography contrast, in vivo brain influx and washout as well as on peripheral metabolism profiles. From 18 initially developed structures, five Tzs were selected to be tested for their in vivo click performance. Whereas all selected structures clicked in vivo to TCO-polymer deposited into the brain, [F-18]18 displayed the most favorable characteristics with respect to brain pretargeting. [F-18]18 is our lead compound for future pretargeted neuroimaging studies based on BBB-penetrant monoclonal antibodies. Pretargeting beyond the BBB will allow us to image targets in the brain that are currently not imageable, such as soluble oligomers of neurodegeneration biomarker proteins. Imaging of such currently non-imageable targets will allow early diagnosis and personalized treatment monitoring. This in turn will accelerate drug development and greatly benefit patient care.
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| 5. |
- van Meer, Floor, et al.
(författare)
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Development and body mass inversely affect children's brain activation in dorsolateral prefrontal cortex during food choice
- 2019
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Ingår i: NeuroImage. - : Elsevier. - 1053-8119 .- 1095-9572. ; 201, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Childhood obesity is a rising problem caused in part by unhealthy food choices. Food choices are based on a neural value signal encoded in the ventromedial prefrontal cortex, and self-control involves modulation of this signal by the dorsolateral prefrontal cortex (dlPFC). We determined the effects of development, body mass (BMI Cole score) and body mass history on the neural correlates of healthy food choice in children. 141 children (aged 10-17y) from Germany, Hungary and Sweden were scanned with fMRI while performing a food choice task. Afterwards health and taste ratings of the foods were collected. In the food choice task children were asked to consider the healthiness or tastiness of the food or to choose naturally. Overall, children made healthier choices when asked to consider healthiness. However, children who had a higher weight gain per year chose less healthy foods when considering healthiness but not when choosing naturally. Pubertal development stage correlated positively while current body mass correlated negatively with dlPFC activation when accepting foods. Pubertal development negatively and current body mass positively influenced the effect of considering healthiness on activation of brain areas involved in salience and motivation. In conclusion, children in earlier stages of pubertal development and children with a higher body weight exhibited less activation in the dlPFC, which has been implicated in self-control during food choice. Furthermore, pubertal development and body mass influenced neural responses to a health cue in areas involved in salience and motivation. Thus, these findings suggest that children in earlier stages of pubertal development, children with a higher body mass gain and children with overweight may possibly be less susceptible to healthy eating interventions that rely on self-control or that highlight health aspects of food.
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