| 1. |
- Qin, Ning, 1990, et al.
(författare)
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Flux regulation through glycolysis and respiration is balanced by inositol pyrophosphates in yeast
- 2023
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 186:4, s. 748-763.e15
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Tidskriftsartikel (refereegranskat)abstract
- Although many prokaryotes have glycolysis alternatives, it's considered as the only energy-generating glucose catabolic pathway in eukaryotes. Here, we managed to create a hybrid-glycolysis yeast. Subsequently, we identified an inositol pyrophosphatase encoded by OCA5 that could regulate glycolysis and respiration by adjusting 5-diphosphoinositol 1,2,3,4,6-pentakisphosphate (5-InsP7) levels. 5-InsP7 levels could regulate the expression of genes involved in glycolysis and respiration, representing a global mechanism that could sense ATP levels and regulate central carbon metabolism. The hybrid-glycolysis yeast did not produce ethanol during growth under excess glucose and could produce 2.68 g/L free fatty acids, which is the highest reported production in shake flask of Saccharomyces cerevisiae. This study demonstrated the significance of hybrid-glycolysis yeast and determined Oca5 as an inositol pyrophosphatase controlling the balance between glycolysis and respiration, which may shed light on the role of inositol pyrophosphates in regulating eukaryotic metabolism.
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| 2. |
- Qin, Ning, et al.
(författare)
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Increased CO 2 fixation enables high carbon-yield production of 3-hydroxypropionic acid in yeast
- 2024
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- CO2 fixation plays a key role to make biobased production cost competitive. Here, we use 3-hydroxypropionic acid (3-HP) to showcase how CO2 fixation enables approaching theoretical-yield production. Using genome-scale metabolic models to calculate the production envelope, we demonstrate that the provision of bicarbonate, formed from CO2, restricts previous attempts for high yield production of 3-HP. We thus develop multiple strategies for bicarbonate uptake, including the identification of Sul1 as a potential bicarbonate transporter, domain swapping of malonyl-CoA reductase, identification of Esbp6 as a potential 3-HP exporter, and deletion of Uga1 to prevent 3-HP degradation. The combined rational engineering increases 3-HP production from 0.14 g/L to 11.25 g/L in shake flask using 20 g/L glucose, approaching the maximum theoretical yield with concurrent biomass formation. The engineered yeast forms the basis for commercialization of bio-acrylic acid, while our CO2 fixation strategies pave the way for CO2 being used as the sole carbon source.
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| 3. |
- Guo, Weiwei, et al.
(författare)
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Aerodynamic effect of wind barriers and running safety of trains on high-speed railway bridges under cross winds
- 2015
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Ingår i: Wind and Structures. - : Techno-Press. - 1226-6116 .- 1598-6225. ; 20:2, s. 213-236
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Tidskriftsartikel (refereegranskat)abstract
- For high-speed railways (HSR) in wind prone regions, wind barriers are often installed on bridges to ensure the running safety of trains. This paper analyzes the effect of wind barriers on the running safety of a high-speed train to cross winds when it passes on a bridge. Two simply-supported (S-S) PC bridges in China, one with 32 m box beams and the other with 16 m trough beams, are selected to perform the dynamic analyses. The bridges are modeled by 3-D finite elements and each vehicle in a train by a multi-rigid-body system connected with suspension springs and dashpots. The wind excitations on the train vehicles and the bridges are numerically simulated, using the static tri-component coefficients obtained from a wind tunnel test, taking into account the effects of wind barriers, train speed and the spatial correlation with wind forces on the deck. The whole histories of a train passing over the two bridges under strong cross winds are simulated and compared, considering variations of wind velocities, train speeds and without or with wind barriers. The threshold curves of wind velocity for train running safety on the two bridges are compared, from which the windbreak effect of the wind barrier are evaluated, based on which a beam structure with better performance is recommended.
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| 4. |
- Li, Wenjie, et al.
(författare)
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La0.75Sr0.25Cr0.5Mn0.5O3-δ-Ce0.8Sm0.2O1.9 as composite electrodes in symmetric solid electrolyte cells for electrochemical removal of nitric oxide
- 2020
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Ingår i: Applied Catalysis B: Environmental. - : Elsevier BV. - 0926-3373. ; 264
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Tidskriftsartikel (refereegranskat)abstract
- Symmetric solid electrolyte cells with La0.75Sr0.25Cr0.5Mn0.5O3-δ (LSCM)-Ce0.8Sm0.2O1.9 (SDC) composite electrodes are employed for nitric oxide (NO) removal. The LSCM powders are synthesized and the cells with LSCM-SDC composite electrodes are fabricated successfully. The results show that moderate SDC addition in LSCM electrode improves the cell performance due to the expansion of three phase boundaries (TPBs). The electrode with 30 wt% SDC has the highest NO conversion of 69.2% and the lowest polarization resistance at 750 °C in 1000 ppm NO. The cathodic polarization activates the cathode because of the Cr/Mn ions reduction, more surface oxygen vacancies and Cr metal exsolution. The cell has good tolerances for H2O, CO2, and SO2, but excess O2 competes with NO for TPBs seriously. The sufficient stability and flexible operation mode of the cell are also proved. Finally, the NO adsorption mechanism on LSCM surface is revealed by density functional theory (DFT) calculations.
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| 5. |
- Li, Xiaozhen
(författare)
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Study of neurodegenerative diseases with novel MRI techniques
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neurodegenerative diseases are a heterogeneous group of disorders that are characterized by the progressive degeneration of structure and function of the nervous system. They include diseases such as Alzheimer’s disease (AD), multiple sclerosis (MS) and others. The main aims of this thesis were to study functional and/or structural brain changes in AD and MS using novel magnetic resonance imaging (MRI) techniques. The concentration of β-amyloid1-42 (Aβ42), total tau (T-tau) and tau phosphorylated at position threonine 181 (P-tau181p) in cerebrospinal fluid (CSF) may reflect brain pathophysiological processes in AD. We found a positive correlation between functional connectivity within the default mode network (DMN) and the ratio of Aβ42/P-tau181p in sporadic AD (Paper I). Furthermore, there were correlations between AD CSF biomarkers and changes of gray matter volume, fractional anisotropy (FA) and mean diffusivity (MD). The majority of brain regions with statistically significant correlation with biomarkers of AD overlapped with the DMN (Paper II). These findings implicate that the brain functional connectivity and structure are affected by pathological changes at an early stage in AD. We also found a significantly increased MD in pre-symptomatic mutation carriers (pre-MCs) of AD compared with non-carriers (NCs), and increased MD associated with AD CSF biomarkers (Paper III). Similar results were observed both in sporadic and familial AD, which suggests that MD may reflect pathology of early stage AD. Although the exact causes of these changes are difficult to identify, the increased MD may be explained by myelin loss. In MS, myelin loss is one of the characteristic events of the pathological process. By combining susceptibility-weighted MRI with analysis of the ?! ∗ decay curves, we were able to characterize and quantify myelin loss (Paper IV). In conclusion, pathological changes in AD and MS could be detected by novel MRI techniques. This suggests that these techniques may also be helpful in further understanding pathology in other neurodegenerative diseases. As non-invasive tools, these novel MRI techniques are possible to screen individuals susceptible to and/or manifesting early neurodegeneration.
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| 6. |
- Li, Xiaozhen, et al.
(författare)
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The Effects of Gene Mutations on Default Mode Network in Familial Alzheimer’s Disease
- 2017
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 56:1, s. 327-334
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Tidskriftsartikel (refereegranskat)abstract
- Familial Alzheimer’s disease (FAD) mutations have very high penetrance but age at onset and rate of disease progression differ. Neuroimaging and cerebrospinal fluid (CSF) examinations in mutation carriers (MCs) may provide an opportunity to identify early biomarkers that can be used to track disease progression from presymptomatic to the dementia stages of disease. The default mode network (DMN) is a resting state neuronal network composed of regions known to associate with amyloid deposition in AD. We hypothesized that functional connectivity in the DMN might change at pre-clinical stages in FAD MCs and correlate with changes in CSF biomarkers as a consequence of AD brain pathology. To test the hypothesis, we compared the functional connectivity in DMN between pre-MCs/MCs and non-carriers (NCs). No significant differences between pre-MCs and NCs were observed. When comparing all MCs with NCs, significant decreased functional connectivity in the right inferior parietal lobule, right precuneus, and left posterior cingulate cortex were found. We also found statistically significant correlations between CSF amyloid-β 42 and tau protein levels and average Z-score, a resting-state functional MRI measurement reflecting the degree of the correlation between a given voxel’s time courses and the time courses corresponding to DMN, from the region with statistical difference. The observed disruption of DMN and pathological levels of AD CSF-biomarkers in FAD MCs are similar to the changes described in sporadic AD, which give further support that amyloid and tau pathology impairs neuronal and synaptic function.
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| 7. |
- Owens-Walton, Conor, et al.
(författare)
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Striatal changes in Parkinson disease : An investigation of morphology, functional connectivity and their relationship to clinical symptoms
- 2018
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Ingår i: Psychiatry Research - Neuroimaging. - : Elsevier BV. - 0925-4927 .- 1872-7506. ; 275, s. 5-13
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Tidskriftsartikel (refereegranskat)abstract
- We sought to investigate morphological and resting state functional connectivity changes to the striatal nuclei in Parkinson disease (PD) and examine whether changes were associated with measures of clinical function. Striatal nuclei were manually segmented on 3T-T1 weighted MRI scans of 74 PD participants and 27 control subjects, quantitatively analysed for volume, shape and also functional connectivity using functional MRI data. Bilateral caudate nuclei and putamen volumes were significantly reduced in the PD cohort compared to controls. When looking at left and right hemispheres, the PD cohort had significantly smaller left caudate nucleus and right putamen volumes compared to controls. A significant correlation was found between greater atrophy of the caudate nucleus and poorer cognitive function, and between greater atrophy of the putamen and more severe motor symptoms. Resting-state functional MRI analysis revealed altered functional connectivity of the striatal structures in the PD group. This research demonstrates that PD involves atrophic changes to the caudate nucleus and putamen that are linked to clinical dysfunction. Our work reveals important information about a key structure-function relationship in the brain and provides support for caudate nucleus and putamen atrophy as neuroimaging biomeasures in PD.
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| 8. |
- Yao, Yao, et al.
(författare)
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The effect of China's Clean Air Act on cognitive function in older adults : a population-based, quasi-experimental study
- 2022
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Ingår i: Lancet Healthy Longevity. - 2666-7568. ; 3:2, s. e98-e108
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Tidskriftsartikel (refereegranskat)abstract
- Background Air pollution might accelerate cognitive ageing; it is unclear whether large-scale interventions, such as China's Clean Air Act (CCAA), can mitigate cognitive deterioration. We aimed to evaluate the effect of CCAA on changes in cognitive function in older adults.Methods In this population-based, quasi-experimental study, we did a difference-in-differences analysis of the data collected during the 2014 and 2018 waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). The study design used a counterfactual analysis feature by dividing CLHLS participants into two groups. The intervention group included participants who lived in areas where the provincial government set a target of reducing particulate matter (PM) by at least 5% annually from 2014 onward, whereas the control group consisted of individuals who lived in areas without a PM reduction target. Global cognitive function was measured using the Mini-Mental State Examination (MMSE). We used fixed-effects models to examine the between-group differences in MMSE score changes before and after CCAA implementation. We associated longitudinal changes in MMSE scores with changes in concentrations of PM with a diameter of less than 2·5 μm (PM2·5) concentration and other regulated pollutants. We used alternative models and sensitivity analyses to evaluate the robustness of the results from the main models.Findings 2812 individuals participated in the 2014 and 2018 surveys (mean age 81·0 years [SD 9·3] in 2014; 1408 [50·1%] female and 1404 [49·9%] male). 2251 (80·0%) were included in the intervention group and 561 (20·0%) in the control group. After controlling for potential confounders, the intervention group had a significantly smaller decline in MMSE scores from 2014 to 2018 compared with the control group: the mean between-group difference was 2·45 points (95% CI 1·32–3·57). Interquartile increases in PM2·5 were associated with a significant MMSE score decline of 0·83 points (95% CI 0·24–1·42); similarly, increases in SO2 were also associated with a significant MMSE score decline of 0·80 points (0·32–1·29).Interpretation Implementing stringent clean air policies might mitigate the risk of air pollutant-associated cognitive ageing in older people.
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