| 1. |
- Li, Shuqi, et al.
(författare)
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Rtt105 functions as a chaperone for replication protein A to preserve genome stability
- 2018
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Ingår i: EMBO Journal. - : Wiley-VCH Verlagsgesellschaft. - 0261-4189 .- 1460-2075. ; 37:17
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Tidskriftsartikel (refereegranskat)abstract
- Generation of single-stranded DNA (ssDNA) is required for the template strand formation during DNA replication. Replication Protein A (RPA) is an ssDNA-binding protein essential for protecting ssDNA at replication forks in eukaryotic cells. While significant progress has been made in characterizing the role of the RPA-ssDNA complex, how RPA is loaded at replication forks remains poorly explored. Here, we show that the Saccharomyces cerevisiae protein regulator of Ty1 transposition 105 (Rtt105) binds RPA and helps load it at replication forks. Cells lacking Rtt105 exhibit a dramatic reduction in RPA loading at replication forks, compromised DNA synthesis under replication stress, and increased genome instability. Mechanistically, we show that Rtt105 mediates the RPA-importin interaction and also promotes RPA binding to ssDNA directly in vitro, but is not present in the final RPA-ssDNA complex. Single-molecule studies reveal that Rtt105 affects the binding mode of RPA to ssDNA These results support a model in which Rtt105 functions as an RPA chaperone that escorts RPA to the nucleus and facilitates its loading onto ssDNA at replication forks.
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| 2. |
- Ding, Jinzhi, et al.
(författare)
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Decadal soil carbon accumulation across Tibetan permafrost regions
- 2017
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Ingår i: Nature Geoscience. - 1752-0894 .- 1752-0908. ; 10:6, s. 420-424
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Tidskriftsartikel (refereegranskat)abstract
- Permafrost soils store large amounts of carbon. Warming can result in carbon release from thawing permafrost, but it can also lead to enhanced primary production, which can increase soil carbon stocks. The balance of these fluxes determines the nature of the permafrost feedback to warming. Here we assessed decadal changes in soil organic carbon stocks in the active layer-the uppermost 30 cm-of permafrost soils across Tibetan alpine regions, based on repeated soil carbon measurements in the early 2000s and 2010s at the same sites. We observed an overall accumulation of soil organic carbon irrespective of vegetation type, with a mean rate of 28.0 g Cm-2 yr(-1) across Tibetan permafrost regions. This soil organic carbon accrual occurred only in the subsurface soil, between depths of 10 and 30 cm, mainly induced by an increase of soil organic carbon concentrations. We conclude that the upper active layer of Tibetan alpine permafrost currently represents a substantial regional soil carbon sink in a warming climate, implying that carbon losses of deeper and older permafrost carbon might be offset by increases in upper-active-layer soil organic carbon stocks, which probably results from enhanced vegetation growth.
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| 3. |
- Lin, Kangming, et al.
(författare)
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Evaluation of an Innovative Point-of-Care Rapid Diagnostic Test for the Identification of Imported Malaria Parasites in China
- 2023
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Ingår i: Tropical Medicine and Infectious Disease. - : MDPI. - 2414-6366. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: China was certified malaria-free by the World Health Organization on 30 June 2021. However, due to imported malaria, maintaining a malaria-free status in China is an ongoing challenge. There are critical gaps in the detection of imported malaria through the currently available tools, especially for non-falciparum malaria. In the study, a novel point-of-care Rapid Diagnostic Test designed for the detection of imported malaria infections was evaluated in the field. Methods: Suspected imported malaria cases reported from Guangxi and Anhui Provinces of China during 2018-2019 were enrolled to evaluate the novel RDTs. Diagnostic performance of the novel RDTs was evaluated based on its sensitivity, specificity, positive and negative predictive values, and Cohen's kappa coefficient, using polymerase chain reaction as the gold standard. The Additive and absolute Net Reclassification Index were calculated to compare the diagnostic performance between the novel RDTs and Wondfo RDTs (control group). Results: A total of 602 samples were tested using the novel RDTs. Compared to the results of PCR, the novel RDTs presented sensitivity, specificity, PPV, NPV, and diagnostic accuracy rates of 78.37%, 95.05%, 94.70%, 79.59%, and 86.21%, respectively. Among the positive samples, the novel RDTs found 87.01%, 71.31%, 81.82%, and 61.54% of P. falciparum, P. ovale, P. vivax, and P. malariae, respectively. The ability to detect non-falciparum malaria did not differ significantly between the novel and Wondfo RDTs (control group). However, Wondfo RDTs can detect more P. falciparum cases than the novel RDTs (96.10% vs. 87.01%, p < 0.001). After the introduction of the novel RDTs, the value of the additive and absolute Net Reclassification Index is 1.83% and 1.33%, respectively. Conclusions: The novel RDTs demonstrated the ability to distinguish P. ovale and P. malariae from P. vivax which may help to improve the malaria post-elimination surveillance tools in China.
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| 4. |
- Li, Xuerui, et al.
(författare)
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Association of life-course reproductive duration with mortality : a population-based twin cohort study
- 2022
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 227:5, s. 748.e1-748.e13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGOUND: Although age at menopause has been linked to mortality, the association between the entire reproductive lifespan and mortality remains unclear.OBJECTIVE: This study aimed to examine to what extent life-course reproductive duration is associated with all-cause mortality and explore the role of a healthy lifestyle and familial background in such an association.STUDY DESIGN: A total of 11,669 women (mean age, 63.54 years) from the Swedish Twin Registry were followed for up to 19 years. Information on reproductive duration (the interval between ages at menarche and menopause) and lifestyle factors (including smoking, alcohol consumption, and physical activity; divided into unfavorable/intermediate/favorable) was collected on the basis of a structured questionnaire. Survival status was obtained from the Sweden Cause of Death Register. The data were analyzed using generalized estimating equation models, Laplace regression, and conditional logistic regression.RESULTS: In the generalized estimating equation model, compared with those with ≤34 reproductive years, the odds ratio (95% confidence interval) of all-cause mortality was 0.79 (0.68–0.90) for those with ≥40 reproductive years, which prolonged survival time by 0.84 (0.24–1.43) years. Women with ≥40 reproductive years plus a favorable lifestyle (odds ratio, 0.28; 95% confidence interval, 0.23–0.35) were at a lower risk of all-cause mortality than those with <40 reproductive years plus an unfavorable lifestyle. An additive interaction between ≥40 reproductive years and a favorable lifestyle on all-cause mortality was observed (attributable proportion, 0.584; 95% confidence interval, 0.016–1.151). The odds ratios in conditional logistic regression and generalized estimating equation models did not differ significantly (P=.67).CONCLUSION: A longer reproductive lifespan is associated with reduced all-cause mortality and prolongs survival by 0.84 years. A favorable lifestyle may amplify the beneficial effect of longer reproductive lifespan on mortality. Familial background does not account for the observed association.
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| 5. |
- Sun, Zhuoyu, et al.
(författare)
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Gestational diabetes mellitus and risks of gynecologic cancers : Results from a nationwide Swedish twin study
- 2021
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 162:1, s. 142-147
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Tidskriftsartikel (refereegranskat)abstract
- Background: Type 2 diabetes has been associated with increased risk of gynecologic cancers, yet the effect of gestational diabetes mellitus (GDM) on gynecologic cancers is unclear.Objectives: To examine associations between GDM history and subsequent gynecologic cancers in parous women, and to explore whether gestational hypertension (GH) plays a role in the associations.Study design: The population-based cohort study included 15,941 individuals from the Swedish Twin Registry. The history of GDM and GH was ascertained based on self-reports. Incident cases of gynecologic cancers (including cancers of the cervix, uterus, ovaries and other female genitalia) were obtained from the National Patients Registry and the Swedish Cancer Registry. Generalized estimating equation models were applied to analyze associations between GDM and gynecologic cancers. Stratified analysis was used to explore whether associations between GDM and gynecologic cancers differed by GH. Additive and multiplicative interactions were calculated between GDM and GH.Results: Of all participants, 350 (2.2%) had GDM, and 1762 (11.1%) had incident gynecologic cancers. No statistically significant associations were found between GDM and risks of any gynecologic cancers. However, GDM was associated with an increased risk of ovarian cancer (OR = 5.29, 95% CI: 1.63–17.19) in women with GH. Interactions between GDM and GH were observed on the additive scale (Attributable proportion due to interaction: 0.86, 95% CI 0.42–1.30, P < 0.001).Conclusions: The associations between GDM and risks of gynecologic cancers were not evident, but the effect of GDM on the risk of ovarian cancer was modified by GH. Further validation in larger cohorts is warranted.
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| 6. |
- Wang, Shuqi, et al.
(författare)
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Association of lifespan reproductive duration with depression in Swedish twins : The role of hormone replacement therapy
- 2023
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Ingår i: International Journal of Gynecology & Obstetrics. - : Wiley. - 0020-7292 .- 1879-3479. ; 162:1, s. 309-316
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the association between reproductive duration and postmenopausal depression (taking the use of hormone replacement therapy [HRT] into account).Methods: In this population-based cohort study, 11 320 postmenopausal women (mean age 63.6 years) were followed for up to 18 years. Reproductive duration was categorized into three groups: short (≤34 years), average (35–39 years), and long (≥40 years). Depression was ascertained from the Sweden National Patient Registry.Results: During the follow up, 593 (5.24%) women developed depression. In the multi-adjusted generalized estimating equation model, the odds ratios (ORs) of depression were 1.28 (95% confidence interval [CI] 1.05–1.55) and 1.25 (95% CI 1.01–1.55) for women with short and long reproductive durations, respectively, compared with those women with average reproductive duration. Women with a non-typical reproductive duration (≤34 or ≥40 years) who received HRT were at a higher risk of depression (OR 1.82, 95% CI 1.42–2.33). There was a significant additive interaction between non-typical reproductive duration and the use of HRT on depression (attributable proportion 0.26, 95% CI 0.03–0.50).Conclusion: Women with a short or long reproductive duration, especially those with a history of HRT use, have a higher risk of depression after menopause compared with those with an average reproductive duration.
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| 7. |
- Wasén, Caroline, 1990, et al.
(författare)
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Bacteroidota inhibit microglia clearance of amyloid-beta and promote plaque deposition in Alzheimer’s disease mouse models
- 2024
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The gut microbiota and microglia play critical roles in Alzheimer’s disease (AD), and elevated Bacteroides is correlated with cerebrospinal fluid amyloid-β (Aβ) and tau levels in AD. We hypothesize that Bacteroides contributes to AD by modulating microglia. Here we show that administering Bacteroides fragilis to APP/PS1-21 mice increases Aβ plaques in females, modulates cortical amyloid processing gene expression, and down regulates phagocytosis and protein degradation microglial gene expression. We further show that administering Bacteroides fragilis to aged wild-type male and female mice suppresses microglial uptake of Aβ1-42 injected into the hippocampus. Depleting murine Bacteroidota with metronidazole decreases amyloid load in aged 5xFAD mice, and activates microglial pathways related to phagocytosis, cytokine signaling, and lysosomal degradation. Taken together, our study demonstrates that members of the Bacteroidota phylum contribute to AD pathogenesis by suppressing microglia phagocytic function, which leads to impaired Aβ clearance and accumulation of amyloid plaques.
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| 8. |
- Xu, Xiayu, et al.
(författare)
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Advances in Smartphone-Based Point-of-Care Diagnostics : This paper reviews the state-of-the-art advances in smartphone-based point-of-care diagnostic technologies and their applications in medicine and biology.
- 2015
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Ingår i: Proceedings of the IEEE. - 0018-9219 .- 1558-2256. ; 103:2, s. 236-247
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Tidskriftsartikel (refereegranskat)abstract
- Point-of-care (POC) diagnostics is playing an increasingly important role in public health, environmental monitoring, and food safety analysis. Smartphones, alone or in conjunction with add-on devices, have shown great capability of data collection, analysis, display, and transmission, making them popular in POC diagnostics. In this article, the state-ofthe- art advances in smartphone-based POC diagnostic technologies and their applications in the past few years are outlined, ranging from in vivo tests that use smartphone’s built-in/external sensors to detect biological signals to in vitro tests that involves complicated biochemical reactions. Novel techniques are illustrated by a number of attractive examples, followed by a brief discussion of the smartphone’s role in telemedicine. The challenges and perspectives of smartphonebased POC diagnostics are also provided.
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