Search

Background: The average human lifespan has increased dramatically over the past century. However, molecular and physiological alterations of the healthy brain during aging remain incompletely understood. Generalized synaptic restructuring may contribute to healthy aging and the reduced metabolism observed in the aged brain. The aim of this study was to assess healthy brain aging using [ 18 F]FDG as a measure of cerebral glucose consumption and [ 11 C]UCB-J PET as an indicator of synaptic density., Method: Using in vivo PET imaging and the novel synaptic-vesicle-glycoprotein 2A (SV2A) radioligand [ 11 C]UCB-J alongside with the fluorodeoxyglucose radioligand [ 18 F]FDG, we obtained SUVR-1 values for 14 pre-defined volume-of-interest brain regions defined on MRI T1 scans. Regional differences in relative [ 18 F]FDG and [ 11 C]UCB-J uptake were investigated using a voxel-wise approach. Finally, correlations between [ 11 C]UCB-J, [ 18 F]FDG PET, and age were examined., Results: We found widespread cortical reduction of synaptic density in a cohort of older HC subjects (N = 15) compared with young HC subjects (N = 11). However, no reduction persisted after partial volume correction and corrections for multiple comparison. Our study confirms previously reported synaptic stability during aging. Regional differences in relative [ 18 F]FDG and [ 11 C]UCB-J uptake were observed with up to 20 % higher [ 11 C]UCB-J uptake in the amygdala and temporal lobe and up to 34 % higher glucose metabolism in thalamus, striatum, occipital, parietal and frontal cortex., Conclusion: In vivo PET using [ 11 C]UCB-J does not support declining synaptic density levels during aging. Thus, loss of synaptic density may be unrelated to aging and does not seem to be a sufficient explanation for the recognized reduction in brain metabolism during aging. Our study also demonstrates that the relationship between glucose consumption and synaptic density is not uniform throughout the human brain with implications for our understanding of neuroenergetics., Competing Interests: Declaration of competing interest Nothing to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Upon investigation of Streptococcus pneumoniae serotype 15F capsular polysaccharide (CPS), we discovered that it had a different phosphorylation substituent, namely glycerol-2-phosphate like the other serogroup 15 CPS rather than the originally reported 0.2 equivalent of phosphate or phosphocholine. Furthermore, we also determined the locations of the two previously unassigned O-acetyl groups present in the repeating unit of the 15F CPS, and carried out full NMR assignments of the 15F as well as 15A CPS. Lastly, a biosynthetic analysis of serotypes 15F and 15A was performed and used to make a prediction for the structure of the recently discovered serotype 15D., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The removal of biomacromolecules from biofluids decreases the sample complexity and lower electrospray suppression effects. Furthermore, it can increase the analysis sensitivity, precision, and selectivity. Often removal approaches evaluate the model based on a single criterion, like protein removed or response of one of few specific metabolites. In this study, we used a multicriteria approach to test the effect of using the solvents methanol and acetonitrile (organic solvent precipitation), trichloroacetic acid (acidic precipitation) and ammonium sulphate (salting out) to remove biomacromolecules from a downstream recovery process from a bacillus fermentation. The downstream recovery process intermediates were analysed using reversed-phase ultra-high-pressure liquid chromatography with electrospray ionisation and high-resolution time-of-flight mass spectrometry detection. To evaluate the pre-treatment agents the following multicriteria was applied i) practical considerations, ii) total amino acid in the precipitated pellet, iii) putative identification of the molecules removed or created by the different treatments, iv) coherence between high quality extracted ion chromatograms (repeatability of DW-CODA) and v) replicate consistency from principal component analysis score values obtained by using the CHEMometric analysis of sections of Selected Ion Chromatograms (CHEMSIC) method. This study presents a generic workflow to find the best pre-treatment for removing bio-macromolecules from biofluids with a multicriteria approach. In our case, the best protein removal strategy for downstream recovery intermediates was acetonitrile precipitation. This method showed high precision, created few artefact peaks compared to simple sample dilution, and mainly removed small peptides., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Methanethiol (MT) is a potent odorant that can be difficult to measure due to its high volatility and reactivity; it easily reacts to form dimethyl disulphide (DMDS) during sampling and/or analysis. This paper focuses on finding an optimal method for sampling and measuring MT with minimum artefact formation using sorbent materials and a thermal desorption-gas chromatography-mass spectrometry method (TD-GC-MS). Experiments were conducted to identify suitable sorbent materials and tubes for analysis. Breakthrough, desorption rate, the effects of storage and desorption temperatures were investigated and different drying methods were established with respect to quantitative sampling and formation of DMDS. Proton-transfer-reaction mass spectrometry (PTR-MS) was used in the development of the method and was an especially useful tool for determination of breakthrough. The results show that glass tubes packed with silica gel for pre-concentration of MT before analysis with TD-GC-MS give the best results. In addition, a combination of Tenax TA and carbonised molecular sieve or Tenax TA cooled to ≤0°C gives acceptable results. 80°C was found to be the optimal desorption temperature. For all the sampling methods tested, storage conditions were observed to be very critical for transformation of MT. Room temperature storage should be limited to few minutes and, in general, tubes should be kept at 0°C or lower during storage., (Copyright © 2012 Elsevier B.V. All rights reserved.)