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- 2019
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Tidskriftsartikel (refereegranskat)
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- Fan, Dong, et al.
(författare)
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Cardiovascular health profiles, systemic inflammation, and physical function in older adults : A population-based study
- 2023
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Ingår i: Archives of gerontology and geriatrics (Print). - : Elsevier BV. - 0167-4943 .- 1872-6976. ; 109
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Tidskriftsartikel (refereegranskat)abstract
- We examined the association of modifiable cardiovascular health (CVH) metrics with physical function among rural older adults in China and the potential role of inflammatory mechanisms in the association. This study included 3733 stroke-and dementia-free participants (age >= 65 years; 56.9% women) in the baseline survey of a multimodal intervention study in rural China. From March-September 2018, data were collected via face-to-face interviews, clinical assessments, and laboratory tests. The Short Performance Physical Battery (SPPB) test was performed to assess physical function. We defined six modifiable CVH metrics according to the modified American Heart Association's recommendations. Serum interleukin (IL)-6 was measured in a subsample (n = 1156). Data were analyzed with multiple general linear and logistic regression models and structural equation modeling. Poor physical function (SPPB score <= 9) was defined in 1443 participants. Ideal CVH (vs. poor CVH) was associated with multivariable-adjusted odds ratio of 0.60 (95%CI 0.48-0.75) for poor physical function. Ideal CVH was significantly associated with higher scores on balance, chair stand, and walking speed tests (all p < 0.05). Moreover, ideal CVH profile was associated with lower serum IL-6 (multivariable-adjusted beta=-0.04; 95% CI-0.06,-0.01). Mediation analysis revealed that serum IL-6 accounted for 14% of the association of CVH with total SPPB score and 10% of the association with walking speed score (p < 0.05). This study suggests that an ideal CVH profile is associated with better physical function among stroke-and dementia-free older adults, partly via inflammatory mechanisms. The preventive implications of these findings warrant further investigation in cohort studies.
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- Song, Lin, et al.
(författare)
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KIBRA controls exosome secretion via inhibiting the proteasomal degradation of Rab27a
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Exosomes are nanosized membrane vesicles released from cells after fusion of multivesicular bodies (MVBs) with the plasma membrane (PM) and play important roles in intercellular communication and numerous biological processes. However, the molecular mechanisms regulating exosome secretion remain poorly understood. Here we identify KIBRA as an adaptor-like protein that stabilizes Rab27a, which in turn controls exosome secretion both in vitro and in vivo. Knockdown or overexpression of KIBRA in neuronal and podocyte cell lines leads to a decrease or increase of exosome secretion, respectively, and KIBRA depletion increases MVB size and number. Comparing protein profiles between KIBRA knockout and wild-type mouse brain showed significantly decreased Rab27a, a small GTPase that regulates MVB-PM docking. Rab27a is stabilized by interacting with KIBRA, which prevents ubiquitination and degradation via the ubiquitin-proteasome pathway. In conclusion, we show that KIBRA controls exosome secretion via inhibiting the proteasomal degradation of Rab27a.
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- Andersson, Martin E, et al.
(författare)
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Structural and mutational studies of the carboxylate cluster in iron-free ribonucleotide reductase R2.
- 2004
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Ingår i: Biochemistry. - 0006-2960. ; 43:24, s. 7966-72
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Tidskriftsartikel (refereegranskat)abstract
- The R2 protein of ribonucleotide reductase features a di-iron site deeply buried in the protein interior. The apo form of the R2 protein has an unusual clustering of carboxylate side chains at the empty metal-binding site. In a previous study, it was found that the loss of the four positive charge equivalents of the diferrous site in the apo protein appeared to be compensated for by the protonation of two histidine and two carboxylate side chains. We have studied the consequences of removing and introducing charged residues on the local hydrogen-bonding pattern in the region of the carboxylate cluster of Corynebacterium ammoniagenes and Escherichia coli protein R2 using site-directed mutagenesis and X-ray crystallography. The structures of the metal-free forms of wild-type C. ammoniagenes R2 and the mutant E. coli proteins D84N, S114D, E115A, H118A, and E238A have been determined and their hydrogen bonding and protonation states have been structurally assigned as far as possible. Significant alterations to the hydrogen-bonding patterns, protonation states, and hydration is observed for all mutant E. coli apo proteins as compared to wild-type apo R2. Further structural variations are revealed by the wild-type apo C. ammoniagenes R2 structure. The protonation and hydration effects seen in the carboxylate cluster appear to be due to two major factors: conservation of the overall charge of the site and the requirement of electrostatic shielding of clustered carboxylate residues. Very short hydrogen-bonding distances between some protonated carboxylate pairs are indicative of low-barrier hydrogen bonding.
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| 7. |
- Dong, Xiao-Fei, et al.
(författare)
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Magnetar Flare-driven Bumpy Declining Light Curves in Hydrogen-poor Superluminous Supernovae
- 2023
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 951:1
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Tidskriftsartikel (refereegranskat)abstract
- Recent observations indicate that hydrogen-poor superluminous supernovae (SLSNe-I) often display bumpy declining light curves. However, the cause of these undulations remains unclear. In this paper, we have improved the magnetar model, which includes flare activities. We present a systematic analysis of a well-observed SLSN-I sample with bumpy light curves in their late phase. These SLSNe-I were identified from multiple transient surveys, such as the Pan-STARRS1 Medium Deep Survey and the Zwicky Transient Facility. Our study provides a set of magnetar-powered model light curve fits for five SLSNe-I, which accurately reproduce the observed light curves using reasonable physical parameters. By extracting the essential characteristics of both the explosions and central engines, these fits provide valuable insights into investigating their potential association with gamma-ray burst engines. We found that the SLSN flares tend to be the dim and long extension of GRB flares in the peak luminosity versus peak time plane. Conducting large-scale, high-cadence surveys in the near future could enhance our comprehension of both SLSN undulating light curve properties and their potential relationship with GRBs by modeling their light curve characteristics.
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| 8. |
- Han, Xiaolei, et al.
(författare)
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Association of Cardiovascular Health Metrics with Dementia in Rural Chinese Older Adults : A Population-Based Study
- 2022
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Ingår i: Clinical Interventions in Aging. - 1176-9092 .- 1178-1998. ; 17, s. 947-956
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We explore the associations of individual and composite cardiovascular health metrics with all-cause dementia, Alzheimer’s disease, and vascular dementia among rural-dwelling older adults and the potential age variations in their associations.Patients and Methods: This community-based cross-sectional study included 4980 older adults (age ≥ 65 years; 57.23% women) from the baseline examination of MIND-China. In March–September 2018, data were collected via face-to-face interviews, clinical examinations, and laboratory test. We defined six cardiovascular health metrics according to the modified American Heart Association’s recommendations. We diagnosed dementia and its subtypes following the international criteria. Data were analyzed using logistic regression models.Results: Of all the participants, 250 were diagnosed with dementia, including 165 with Alzheimer’s disease and 75 with vascular dementia. Ideal composite global cardiovascular health metrics (vs poor composite metrics) were associated with a multi-adjusted odds ratio (95% confidence interval) of 0.62 (0.42– 0.93) for dementia, 0.88 (0.52– 1.48) for Alzheimer’s disease, and 0.31 (0.16– 0.60) for vascular dementia. Moreover, ideal biological cardiovascular health metrics were associated with multi-adjusted odds ratio of 0.52 (0.28– 0.95) for dementia and 0.21 (0.06– 0.77) for vascular dementia in young–old adults (65– 74 years), whereas ideal behavioral cardiovascular health metrics were associated with multi-adjusted odds ratio of 0.48 (0.26– 0.89) for dementia and 0.16 (0.06– 0.43) for vascular dementia in old–old adults (≥ 75 years).Conclusion: Our results suggest that ideal cardiovascular health metrics are cross-sectionally associated with a low likelihood of dementia and vascular dementia among rural-dwelling older Chinese adults. The associations vary with age, components of cardiovascular health metrics, and dementia subtypes.
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| 9. |
- Han, Xiaolei, et al.
(författare)
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Sex disparities in cardiovascular health metrics among rural-dwelling older adults in China : a population-based study
- 2021
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Ingår i: BMC Geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cardiovascular health (CVH) metrics among Chinese older adults are poorly understood. We investigated sex disparities in CVH metrics and their management among rural-dwelling older adults in China.Methods: This community-based study included 5026 participants (age >= 65years; 57.2% women) in the baseline survey of a multimodal intervention study in rural China. In March-September 2018, data were collected through face-to-face interviews, clinical examinations, and laboratory tests. We defined six CVH metrics (three behavioral factors-smoking, body mass index, and physical activity; three biological factors-blood pressure, total cholesterol, and blood glucose) following the modified American Heart Association's recommendations. We performed descriptive analysis separately for men and women.Results: Of all participants, only 0.8% achieved ideal levels in all six CVH metrics. Men were more likely than women to have ideal levels in all CVH metrics but smoking. Women had higher prevalence of ideal global (9.7% vs. 7.8%) and behavioral (18.3% vs. 9.5%) CVH metrics (p<0.001), whereas men had higher prevalence of ideal biological CVH metrics (5.4% vs. 3.5%, p<0.001). The prevalence of ideal global and behavioral CVH metrics increased with age in both women and men (p for trend<0.001). Women were more likely to be aware of their hypertension and diabetes, and to receive antihypertensive treatment, while men were more likely to achieve the goal of high cholesterol treatment (p<0.05).Conclusions: The CVH metrics among older adults living in the rural communities in China are characterized by an extremely low proportion of optimal global CVH metrics and distinct sex differences, alongside poor management of major biological risk factors.
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| 10. |
- Liang, Yajun, et al.
(författare)
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Migraine, Cognitive Decline, and Dementia in Older Adults : A Population-Based Study.
- 2022
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 88:1, s. 263-271
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The potential impact of migraine on cognitive aging among older adults remains controversial.OBJECTIVE: To examine the relationship of migraine and subtypes with cognitive decline and dementia in an older Swedish population.METHODS: This population-based study included 3069 participants (age≥60) from the Swedish National study on Aging and Care in Kungsholmen, Stockholm. Baseline examination was conducted in 2001-2004, and participants were followed every 3 or 6 years until 2013-2016. Data were collected through face-to-face interviews, clinical examinations, laboratory tests, and linkage with registers. Global cognitive function was measured with the Mini-Mental State Examination (MMSE). Dementia was diagnosed according to the DSM-IV criteria. Migraine and subtypes were defined following the international classification system. Data were analyzed using logistic regression, Cox regression, and linear mixed-effects models.RESULTS: At baseline, 305 participants were defined with non-migraine headache and 352 with migraine. The cross-sectional analysis showed that the multivariable-adjusted odds ratio (95% confidence interval) of prevalent dementia was 0.49 (0.20-1.21) for migraine and 0.66 (0.26-1.66) for migraine without aura. The longitudinal analysis showed that the multivariable-adjusted hazard ratios of incident dementia associated with migraine and subtypes ranged 0.68-0.89 (p > 0.05). Furthermore, migraine and subtypes were not significantly associated with either baseline MMSE score or MMSE changes during follow-ups (p > 0.05). The nonsignificant associations did not vary substantially by age, APOEɛ4 allele, cerebrovascular disease, and antimigraine treatment (p for interactions > 0.05).CONCLUSION: This study shows no evidence supporting the associations of migraine and its subtypes with cognitive decline and dementia among older adults.
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