| 1. |
- Brunius, Carl, 1974, et al.
(författare)
-
Prediction and modeling of pre-analytical sampling errors as a strategy to improve plasma NMR metabolomics data
- 2017
-
Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1460-2059 .- 1367-4811. ; 33:22, s. 3567-3574
-
Tidskriftsartikel (refereegranskat)abstract
- Biobanks are important infrastructures for life science research. Optimal sample handling regarding e.g. collection and processing of biological samples is highly complex, with many variables that could alter sample integrity and even more complex when considering multiple study centers or using legacy samples with limited documentation on sample management. Novel means to understand and take into account such variability would enable high-quality research on archived samples. This study investigated whether pre-analytical sample variability could be predicted and reduced by modeling alterations in the plasma metabolome, measured by NMR, as a function of pre-centrifugation conditions (1-36 h pre-centrifugation delay time at 4 A degrees C and 22 A degrees C) in 16 individuals. Pre-centrifugation temperature and delay times were predicted using random forest modeling and performance was validated on independent samples. Alterations in the metabolome were modeled at each temperature using a cluster-based approach, revealing reproducible effects of delay time on energy metabolism intermediates at both temperatures, but more pronounced at 22 A degrees C. Moreover, pre-centrifugation delay at 4 A degrees C resulted in large, specific variability at 3 h, predominantly of lipids. Pre-analytical sample handling error correction resulted in significant improvement of data quality, particularly at 22 A degrees C. This approach offers the possibility to predict pre-centrifugation delay temperature and time in biobanked samples before use in costly downstream applications. Moreover, the results suggest potential to decrease the impact of undesired, delay-induced variability. However, these findings need to be validated in multiple, large sample sets and with analytical techniques covering a wider range of the metabolome, such as LC-MS.
|
|
| 2. |
- Gupta, G., et al.
(författare)
-
Exploiting Mass Spectrometry to Unlock the Mechanism of Nanoparticle-Induced Inflammasome Activation
- 2023
-
Ingår i: Acs Nano. - : AMER CHEMICAL SOC. - 1936-0851 .- 1936-086X. ; 17:17
-
Tidskriftsartikel (refereegranskat)abstract
- Nanoparticles (NPs) elicit sterile inflammation, but the underlying signaling pathways are poorly understood. Here, we report that human monocytes are particularly vulnerable to amorphous silica NPs, as evidenced by single-cell-based analysis of peripheral blood mononuclear cells using cytometry by time-of-flight (CyToF), while silane modification of the NPs mitigated their toxicity. Using human THP-1 cells as a model, we observed cellular internalization of silica NPs by nanoscale secondary ion mass spectrometry (nanoSIMS) and this was confirmed by transmission electron microscopy. Lipid droplet accumulation was also noted in the exposed cells. Furthermore, time-of-flight secondary ion mass spectrometry (ToF-SIMS) revealed specific changes in plasma membrane lipids, including phosphatidylcholine (PC) in silica NP-exposed cells, and subsequent studies suggested that lysophosphatidylcholine (LPC) acts as a cell autonomous signal for inflammasome activation in the absence of priming with a microbial ligand. Moreover, we found that silica NPs elicited NLRP3 inflammasome activation in monocytes, whereas cell death transpired through a non-apoptotic, lipid peroxidation-dependent mechanism. Together, these data further our understanding of the mechanism of sterile inflammation.
|
|
| 3. |
- Hanrieder, Jörg, 1980, et al.
(författare)
-
High Resolution Metabolite Imaging in the Hippocampus Following Neonatal Exposure to the Environmental Toxin BMAA Using ToF-SIMS
- 2014
-
Ingår i: Acs Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 5:7, s. 568-575
-
Tidskriftsartikel (refereegranskat)abstract
- The environmental neurotoxin beta-N-methylamino-L-alanine (BMAA) is suggested to be linked with neurodegenerative disease. In a rat model, neonatal exposure to BMAA induced selective uptake in the hippocampus and caused cell loss, mineralization and astrogliosis as well as learning and memory impairments in adulthood. Moreover, neonatal exposure resulted in increased protein ubiquitination in the cornus ammonis 1 (CA1) region of the adult hippocampus indicating that BMAA may induce protein aggregation. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) based imaging is a powerful technology for spatial profiling of small molecular weight compounds in biological tissues with high chemical specificity and high spatial resolution. The aim of this study was to characterize neurochemical changes in the hippocampus of six month-old rats treated neonatally (postnatal days 9-10) with BMAA. Multivariate data analysis of whole section ToF-SIMS scans was performed to delineate anatomical regions of interest based on their chemical distribution pattern. Further analysis of spectral data obtained from the outlined anatomical regions, including CA1 and dentate gyms (DG) revealed BMAA-induced long-term changes. Increased levels of phospholipids and protein fragments in the histopathologically altered CA1 region as well as phosphate depletion in the DG were observed. Moreover, high resolution SIMS imaging revealed a specific localization of phosphatidylcholine lipids, protein signals and potassium in the histopathologically altered CA1 These findings demonstrate that ToF-SIMS based imaging is a powerful approach for probing biochemical changes in situ and might serve as promising technique for investigating neurotoxin-induced brain pathology.
|
|
| 4. |
- Hedblom, Marcus, et al.
(författare)
-
Reduction of physiological stress by urban green space in a multisensory virtual experiment
- 2019
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Although stress is an increasing global health problem in cities, urban green spaces can provide health benefits. There is, however, a lack of understanding of the link between physiological mechanisms and qualities of urban green spaces. Here, we compare the effects of visual stimuli (360 degree virtual photos of an urban environment, forest, and park) to the effects of congruent olfactory stimuli (nature and city odours) and auditory stimuli (bird songs and noise) on physiological stress recovery. Participants (N = 154) were pseudo-randomised into participating in one of the three environments and subsequently exposed to stress (operationalised by skin conductance levels). The park and forest, but not the urban area, provided significant stress reduction. High pleasantness ratings of the environment were linked to low physiological stress responses for olfactory and to some extent for auditory, but not for visual stimuli. This result indicates that olfactory stimuli may be better at facilitating stress reduction than visual stimuli. Currently, urban planners prioritise visual stimuli when planning open green spaces, but urban planners should also consider multisensory qualities.
|
|
| 5. |
- Hedblom, Marcus, et al.
(författare)
-
Sounds of Nature in the City: No Evidence of Bird Song Improving Stress Recovery
- 2019
-
Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601 .- 1661-7827. ; 16:8
-
Tidskriftsartikel (refereegranskat)abstract
- Noise from city traffic is one of the most significant environmental stressors. Natural soundscapes, such as bird songs, have been suggested to potentially mitigate or mask noise. All previous studies on masking noise use self-evaluation data rather than physiological data. In this study, while respondents (n = 117) watched a 360 degrees virtual reality (VR) photograph of a park, they were exposed to different soundscapes and mild electrical shocks. The soundscapesbird song, bird song and traffic noise, and traffic noisewere played during a 10 min recovery period while their skin conductance levels were assessed as a measure of arousal/stress. No significant difference in stress recovery was found between the soundscapes although a tendency for less stress in bird song and more stress in traffic noise was noted. All three soundscapes, however, significantly reduced stress. This result could be attributed to the stress-reducing effect of the visual VR environment, to the noise levels being higher than 47 dBA (a level known to make masking ineffective), or to the respondents finding bird songs stressful. Reduction of stress in cities using masking with natural sounds requires further studies with not only larger samples but also sufficient methods to detect potential sex differences.
|
|
| 6. |
- Landberg, Rikard, 1981, et al.
(författare)
-
New alkylresorcinol metabolites in spot urine as biomarkers of whole grain wheat and rye intake in a Swedish middle-aged population
- 2018
-
Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 72:10, s. 1439-1446
-
Tidskriftsartikel (refereegranskat)abstract
- Background/objectives: Studies on the health effects of whole grains typically use self-reported intakes which are prone to large measurement errors. Dietary biomarkers that can provide an objective measure of intake are needed. New alkylresorcinol (AR) metabolites (3,5-dihydroxycinnamic acid (DHCA), 2-(3,5-dihydroxybenzamido)acetic acid (DHBA-glycine) and 5-(3,5-dihydroxyphenyl) pentanoic acid (DHPPTA)) in 24 h urine samples have been suggested as biomarkers for whole grain (WG) wheat and rye intake but remain to be evaluated in spot urine samples. Subjects/methods: The reproducibility of the new AR metabolites (DHCA, DHBA-glycine and DHPPTA) was investigated in 4 repeated samples over a period of 2 wk in spot urine from 40 Swedish men and women enroled in the SCAPIS-study, after adjustment of creatinine. Metabolite concentrations were correlated with total whole grain intake estimated during the same period. Results: The medium-term reproducibility determined for DHCA, DHPPTA and DHBA-glycine varied from moderate to excellent (intra-class correlation coefficient = 0.35–0.67). Moreover, DHCA and DHBA-glycine were independently associated with self-reported total WG intake (β = 0.18, P = 0.08 and β = 0.18, P = 0.02, respectively) and all metabolites except for DHPPA were higher among women. Conclusions: This study supports the idea of using AR metabolites in one or several spot urine samples as biomarkers of whole grain intake. These findings need to be confirmed in different populations.
|
|
