| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Franic, Iva, et al.
(författare)
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Climate, host and geography shape insect and fungal communities of trees
- 2023
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Non-native pests, climate change, and their interactions are likely to alter relationships between trees and tree-associated organisms with consequences for forest health. To understand and predict such changes, factors structuring tree-associated communities need to be determined. Here, we analysed the data consisting of records of insects and fungi collected from dormant twigs from 155 tree species at 51 botanical gardens or arboreta in 32 countries. Generalized dissimilarity models revealed similar relative importance of studied climatic, host-related and geographic factors on differences in tree-associated communities. Mean annual temperature, phylogenetic distance between hosts and geographic distance between locations were the major drivers of dissimilarities. The increasing importance of high temperatures on differences in studied communities indicate that climate change could affect tree-associated organisms directly and indirectly through host range shifts. Insect and fungal communities were more similar between closely related vs. distant hosts suggesting that host range shifts may facilitate the emergence of new pests. Moreover, dissimilarities among tree-associated communities increased with geographic distance indicating that human-mediated transport may serve as a pathway of the introductions of new pests. The results of this study highlight the need to limit the establishment of tree pests and increase the resilience of forest ecosystems to changes in climate.
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| 3. |
- Franic, Iva, et al.
(författare)
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Worldwide diversity of endophytic fungi and insects associated with dormant tree twigs
- 2022
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Ingår i: Scientific Data. - : Nature Publishing Group. - 2052-4463. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- International trade in plants and climate change are two of the main factors causing damaging tree pests (i.e. fungi and insects) to spread into new areas. To mitigate these risks, a large-scale assessment of tree-associated fungi and insects is needed. We present records of endophytic fungi and insects in twigs of 17 angiosperm and gymnosperm genera, from 51 locations in 32 countries worldwide. Endophytic fungi were characterized by high-throughput sequencing of 352 samples from 145 tree species in 28 countries. Insects were reared from 227 samples of 109 tree species in 18 countries and sorted into taxonomic orders and feeding guilds. Herbivorous insects were grouped into morphospecies and were identified using molecular and morphological approaches. This dataset reveals the diversity of tree-associated taxa, as it contains 12,721 fungal Amplicon Sequence Variants and 208 herbivorous insect morphospecies, sampled across broad geographic and climatic gradients and for many tree species. This dataset will facilitate applied and fundamental studies on the distribution of fungal endophytes and insects in trees.
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| 4. |
- Lahmann, Petra H., et al.
(författare)
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Anthropometric measures and epithelial ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition
- 2010
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 126:10, s. 2404-2415
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Tidskriftsartikel (refereegranskat)abstract
- We examined the associations of measured anthropometric factors, including general and central adiposity and height, with ovarian cancer risk. We also investigated these associations by menopausal status and for specific histological subtypes. Among 226,798 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, there were 611 incident cases of primary, malignant, epithelial ovarian cancer diagnosed during a mean 8.9 years of follow-up. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (as), adjusted for potential confounders. Compared to women with body mass index (BMI) < 25 kg/m(2), obesity (BMI >= 30 kg/m(2)) was associated with excess ovarian cancer risk for all women combined (HR = 1.33, 95% Cl = 1.05-1.68; p(trend) = 0.02) and postmenopausal women (HR = 1.59, 95% Cl = 1.20-2.10; p(trend) = 0.001), but the association was weaker for premenopausal women (HR = 1.16, 95% Cl = 0.65-2.06; p(trend) = 0.65). Neither height or weight gain, nor BMI-adjusted measures of fat distribution assessed by waist circumference, waist-hip ratio (WHR) or hip circumference were associated with overall risk. WHR was related to increased risk of mucinous tumors (BMI-adjusted HR per 0.05 unit increment = 1.17, 95% Cl = 1.00-1.38). For all women combined, no other significant associations with risk were observed for specific histological subtypes. This large, prospective study provides evidence that obesity is an important modifiable risk factor for epithelial ovarian cancer, particularly among postmenopausal women.
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| 5. |
- Vergnaud, Anne-Claire, et al.
(författare)
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Adherence to the World Cancer Research Fund/American Institute for Cancer Research guidelines and risk of death in Europe : results from the European Prospective Investigation into Nutrition and Cancer cohort study
- 2013
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 97:5, s. 1107-1120
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Tidskriftsartikel (refereegranskat)abstract
- Background: In 2007, the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) issued recommendations on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence. Objective: We investigated whether concordance with WCRF/AICR recommendations is related to risk of death. Design: The current study included 378,864 participants from 9 European countries enrolled in the European Prospective Investigation into Cancer and Nutrition study. At recruitment (1992-1998), dietary, anthropometric, and lifestyle information was collected. A WCRF/AICR score, which incorporated 6 of the WCRF/AICR recommendations for men [regarding body fatness, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, and alcoholic drinks (score range: 0-6)] and 7 WCRF/AICR recommendations for women [plus breastfeeding (score range: 0-7)], was constructed. Higher scores indicated greater concordance with WCRF/AICR recommendations. Associations between the WCRF/AICR score and risks of total and cause-specific death were estimated by using Cox regression analysis. Results: After a median follow-up time of 12.8 y, 23,828 deaths were identified. Participants within the highest category of the WCRF/AICR score (5-6 points in men; 6-7 points in women) had a 34% lower hazard of death (95% CI: 0.59, 0.75) compared with participants within the lowest category of the WCRF/AICR score (0-2 points in men; 0-3 points in women). Significant inverse associations were observed in all countries. The WCRF/AICR score was also significantly associated with a lower hazard of dying from cancer, circulatory disease, and respiratory disease. Conclusion: Results of this study suggest that following WCRF/AICR recommendations could significantly increase longevity.
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| 6. |
- Aglago, Elom K., et al.
(författare)
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Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort
- 2020
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565 .- 1542-7714. ; 18:3, s. 6-666
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. Results: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80–0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82–0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83–1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78–0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18–1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026). Conclusions: In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.
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| 7. |
- Aleksandrova, Krasimira, et al.
(författare)
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Development and validation of a lifestyle-based model for colorectal cancer risk prediction : the LiFeCRC score
- 2021
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population. Methods: The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992–2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed. Results: The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell’s C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement = 0.307 (95% CI 0.264–0.352)), and especially for young individuals below 45 years (continuous net reclassification improvement = 0.364 (95% CI 0.084–0.575)). Conclusions: LiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level.
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| 8. |
- May, Anne M., et al.
(författare)
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Determinants of non- response to a second assessment of lifestyle factors and body weight in the EPIC-PANACEA study
- 2012
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Ingår i: BMC Medical Research Methodology. - : BioMed Central. - 1471-2288. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: This paper discusses whether baseline demographic, socio-economic, health variables, length of follow-up and method of contacting the participants predict non-response to the invitation for a second assessment of lifestyle factors and body weight in the European multi-center EPIC-PANACEA study. Methods: Over 500.000 participants from several centers in ten European countries recruited between 1992 and 2000 were contacted 2-11 years later to update data on lifestyle and body weight. Length of follow-up as well as the method of approaching differed between the collaborating study centers. Non-responders were compared with responders using multivariate logistic regression analyses. Results: Overall response for the second assessment was high (81.6%). Compared to postal surveys, centers where the participants completed the questionnaire by phone attained a higher response. Response was also high in centers with a short follow-up period. Non-response was higher in participants who were male (odds ratio 1.09 (confidence interval 1.07; 1.11), aged under 40 years (1.96 (1.90; 2.02), living alone (1.40 (1.37; 1.43), less educated (1.35 (1.12; 1.19), of poorer health (1.33 (1.27; 1.39), reporting an unhealthy lifestyle and who had either a low (<18.5 kg/m2, 1.16 (1.09; 1.23)) or a high BMI (>25, 1.08 (1.06; 1.10); especially >= 30 kg/m2, 1.26 (1.23; 1.29)). Conclusions: Cohort studies may enhance cohort maintenance by paying particular attention to the subgroups that are most unlikely to respond and by an active recruitment strategy using telephone interviews.
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| 9. |
- Peters, Tricia, et al.
(författare)
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Validity of a short questionnaire to assess physical activity in 10 European countries
- 2012
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Ingår i: European Journal of Epidemiology. - Dordrecht : Springer Netherlands. - 0393-2990 .- 1573-7284. ; 27:1, s. 15-25
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Tidskriftsartikel (refereegranskat)abstract
- To accurately examine associations of physical activity (PA) with disease outcomes, a valid method of assessing free-living activity is required. We examined the validity of a brief PA questionnaire (PAQ) used in the European Prospective Investigation into Cancer and Nutrition (EPIC). PA energy expenditure (PAEE) and time spent in moderate and vigorous physical activity (MVPA) was measured in 1,941 healthy individuals from 10 European countries using individually-calibrated combined heart-rate and movement sensing. Participants also completed the short EPIC-PAQ, which refers to past year's activity. Pearson (r) and Spearman (sigma) correlation coefficients were calculated for each country, and random effects meta-analysis was used to calculate the combined correlation across countries to estimate the validity of two previously- and one newly-derived ordered, categorical PA indices ("Cambridge index", "total PA index", and "recreational index") that categorized individuals as inactive, moderately inactive, moderately active, or active. The strongest associations with PAEE and MVPA were observed for the Cambridge index (r = 0.33 and r = 0.25, respectively). No significant heterogeneity by country was observed for this index (I-2 = 36.3%, P = 0.12; I-2 = 0.0%, P = 0.85), whereas heterogeneity was suggested for other indices (I-2 > 48%, P < 0.05, I-2 > 47%, P < 0.05). PAEE increased linearly across self-reported PA categories (P for trend < 0.001), with an average difference of approximately 460 kJ/d for men and 365 kJ/d for women, between categories of the Cambridge index. The EPIC-PAQ is suitable for categorizing European men and women into four distinct categories of overall physical activity. The difference in PAEE between categories may be useful when estimating effect sizes from observational research.
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| 10. |
- Ried, Janina S., et al.
(författare)
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A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
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